Diagnosis and Management of Acute Pancreatitis.

Acute pancreatitis (AP) is increasing in incidence across the world, and in all age groups. Major changes in management have occurred in the last decade. Avoiding total parenteral nutrition and prophylactic antibiotics, avoiding overly aggressive fluid resuscitation, initiating early feeding, avoiding endoscopic retrograde cholangiopancreatography in the absence of concomitant cholangitis, same-admission cholecystectomy, and minimally invasive approaches to infected necrosis should now be standard of care. Increasing recognition of the risk of recurrence of AP, and progression to chronic pancreatitis, along with the unexpectedly high risk of diabetes and exocrine insufficiency after AP is the subject of large ongoing studies. In this review, we provide an update on important changes in management for this increasingly common disease.

Healthcare disparities in pancreatitis: knowledge gaps and next steps.

PURPOSE OF REVIEW: This review examines current research on healthcare disparities in pancreatitis, identifies knowledge gaps, and proposes strategies to develop targeted multilevel interventions to address inequities in pancreatitis care. RECENT FINDINGS: Current literature has identified patient, disease, and healthcare-level factors contributing to disparities in risk factors and health outcomes of pancreatitis. Moreover, social structures, economic systems, social vulnerability, and policy significantly influence the pancreatitis care continuum. SUMMARY: Understanding the root causes of health inequities is critical to developing effective approaches for the prevention, early detection, and management of pancreatitis.

Alterations in microbiome associated with acute pancreatitis.

PURPOSE OF REVIEW: This review evaluates the current knowledge of gut microbiome alterations in acute pancreatitis, including those that can increase acute pancreatitis risk or worsen disease severity, and the mechanisms of gut microbiome driven injury in acute pancreatitis. RECENT FINDINGS: Recent observational studies in humans showed the association of gut microbiome changes (decreased gut microbiome diversity, alterations in relative abundances of certain species, and association of unique species with functional pathways) with acute pancreatitis risk and severity. Furthermore, in-vivo studies highlighted the role of gut microbiome in the development and severity of acute pancreatitis using FMT models. The gut barrier integrity, immune cell homeostasis, and microbial metabolites appear to play key roles in acute pancreatitis risk and severity. SUMMARY: Large human cohort studies that assess gut microbiome profile, its metabolites and impact on acute pancreatitis risk and severity will be crucial for development of innovative prediction, prevention and treatment strategies.

A review of deep learning and radiomics approaches for pancreatic cancer diagnosis from medical imaging.

PURPOSE OF REVIEW: Early and accurate diagnosis of pancreatic cancer is crucial for improving patient outcomes, and artificial intelligence (AI) algorithms have the potential to play a vital role in computer-aided diagnosis of pancreatic cancer. In this review, we aim to provide the latest and relevant advances in AI, specifically deep learning (DL) and radiomics approaches, for pancreatic cancer diagnosis using cross-sectional imaging examinations such as computed tomography (CT) and magnetic resonance imaging (MRI). RECENT FINDINGS: This review highlights the recent developments in DL techniques applied to medical imaging, including convolutional neural networks (CNNs), transformer-based models, and novel deep learning architectures that focus on multitype pancreatic lesions, multiorgan and multitumor segmentation, as well as incorporating auxiliary information. We also discuss advancements in radiomics, such as improved imaging feature extraction, optimized machine learning classifiers and integration with clinical data. Furthermore, we explore implementing AI-based clinical decision support systems for pancreatic cancer diagnosis using medical imaging in practical settings. SUMMARY: Deep learning and radiomics with medical imaging have demonstrated strong potential to improve diagnostic accuracy of pancreatic cancer, facilitate personalized treatment planning, and identify prognostic and predictive biomarkers. However, challenges remain in translating research findings into clinical practice. More studies are required focusing on refining these methods, addressing significant limitations, and developing integrative approaches for data analysis to further advance the field of pancreatic cancer diagnosis.

An assessment of pancreatology education in North American pediatric gastroenterology fellowship programs.

BACKGROUND/OBJECTIVES: Within the last two decades, an increased incidence of acute pancreatitis (AP) has been reported in childhood, with some progressing to acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). Training future pancreatologists is critical to improve the care of children with pancreatic diseases. There are no studies to assess whether the pediatric gastroenterology (GI) fellowship curriculum prepares specialists to care for children with pancreatic diseases. METHODS: An electronic survey was distributed to all North American Pediatric Gastroenterology Fellows. The survey included 31 questions on pancreatology training including academic resources, research experience, clinical exposure, clinical confidence, and career plans. RESULTS: A total of 112 (25.8%) fellows responded from 41 (41/72, 56.9%) training centers in North America. Pancreas-specific didactic lectures were reported by 90.2% (n = 101); 49.5% (50/101) had at least quarterly or monthly lectures. Clinical confidence (Likert 4-5) was highest in managing and treating AP (94.6% and 93.8% respectively), relatively lower for ARP (84.8% and 71.4%) and lowest for CP (63.4% and 42.0%). Confidence in diagnosing both ARP and CP was associated with the variety of pancreatic diseases seen (p < 0.001) and total number of patients followed over a 6 month period (p = 0.04). Nine (8%) reported interest in specializing in pancreatology, 12 (10.7%) in pursuing research in the pancreatology. CONCLUSIONS: Trainee confidence is highest in managing AP, lowest in CP, and seems to be directly correlated with the variety of pancreatic diseases and number of patients followed. Continued commitment is necessary to foster training of the next generation of pediatric pancreatologists.

Race-dependent association of sulfidogenic bacteria with colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) incidence is higher in African Americans (AAs) compared with non-Hispanic whites (NHWs). A diet high in animal protein and fat is an environmental risk factor for CRC development. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC. Hydrogen sulfide, produced by autochthonous sulfidogenic bacteria, triggers proinflammatory pathways and hyperproliferation, and is genotoxic. We hypothesised that sulfidogenic bacterial abundance in colonic mucosa may be an environmental CRC risk factor that distinguishes AA and NHW. DESIGN: Colonic biopsies from uninvolved or healthy mucosa from CRC cases and tumour-free controls were collected prospectively from five medical centres in Chicago for association studies. Sulfidogenic bacterial abundance in uninvolved colonic mucosa of AA and NHW CRC cases was compared with normal mucosa of AA and NHW controls. In addition, 16S rDNA sequencing was performed in AA cases and controls. Correlations were examined among bacterial targets, race, disease status and dietary intake. RESULTS: AAs harboured a greater abundance of sulfidogenic bacteria compared with NHWs regardless of disease status. Bilophila wadsworthia-specific dsrA was more abundant in AA cases than controls. Linear discriminant analysis of 16S rRNA gene sequences revealed five sulfidogenic genera that were more abundant in AA cases. Fat and protein intake and daily servings of meat were significantly higher in AAs compared with NHWs, and multiple dietary components correlated with a higher abundance of sulfidogenic bacteria. CONCLUSIONS: These results implicate sulfidogenic bacteria as a potential environmental risk factor contributing to CRC development in AAs.

Breath Methane Levels Are Increased Among Patients with Diverticulosis.

BACKGROUND: Diverticulosis and its complications are important healthcare problems in the USA and throughout the Western world. While mechanisms as to how diverticulosis occurs have partially been explored, few studies examined the relationship between colonic gases such as methane and diverticulosis in humans. AIM: This study aimed to demonstrate a significant relationship between methanogenic Archaea and development of diverticulosis. METHODS: Subjects who consecutively underwent hydrogen breath test at Rush University Medical Center between 2003 and 2010 were identified retrospectively through a database. Medical records were reviewed for presence of a colonoscopy report. Two hundred and sixty-four subjects were identified who had both a breath methane level measurement and a colonoscopy result. Additional demographic and clinical data were obtained with chart review. RESULTS: Mean breath methane levels were higher in subjects with diverticulosis compared to those without diverticulosis (7.89 vs. 4.94 ppm, p = 0.04). Methane producers (defined as those with baseline fasting breath methane level >5 ppm) were more frequent among subjects with diverticulosis compared to those without diverticulosis (50.9 vs. 34 %, p = 0.0025). When adjusted for confounders, breath methane levels and age were the two independent predictors of diverticulosis on colonoscopy with logistic regression modeling. CONCLUSIONS: Methanogenesis is associated with the presence of diverticulosis. Further studies are needed to confirm our findings and prospectively evaluate a possible etiological role of methanogenesis and methanogenic archaea in diverticulosis.

Risk factors for severe or fatal drug-induced liver injury from amoxicillin-clavulanic acid.

AIM: To identify risk factors for severe liver injury or mortality from drug-induced liver injury (DILI) from amoxicillin-clavulanic acid. To determine if co-administration of potentially hepatotoxic drugs was associated with an increased risk of DILI from amoxicillin-clavulanic acid. METHODS: We conducted a systematic review of the published work and data extraction of articles on DILI injury from amoxicillin-clavulanic acid. Potentially hepatotoxic drugs were defined as medications with DILI listed in the package insert or reported in the published work. Individual patient data were entered into an SPSS (version 17.0; Chicago, IL, USA) database and were analyzed using the χ(2) -test or Fisher's exact test; Student's t-test; and non-parametric tests such as Mann-Whitney U-test as appropriate. RESULTS: We identified 3932 articles of which 41 publications with 255 reported cases met inclusion criteria. Mortality from DILI from amoxicillin-clavulanic acid was increased among patients receiving concomitant potentially hepatotoxic drugs compared with patients not on concomitant potential hepatotoxic drugs (21.4% [3/14] vs 2.3% [2/89], P = 0.017]. The most common classes of concomitant drugs were: antimicrobials, analgesics and hormonal therapy. Female patients were more likely to receive a concomitant potentially hepatotoxic medication (25% vs 9.1% for men, P = 0.05). CONCLUSION: Patients who developed severe or fatal DILI from amoxicillin-clavulanic acid were more likely to be on concomitant hepatotoxic medications. Female patients were more likely to receive concomitant hepatotoxic drugs. Further studies are needed to investigate drug interaction between amoxicillin-clavulanic acid and concomitant potentially hepatotoxic drugs.

Histological Remission of Eosinophilic Esophagitis Following Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia.

Eosinophilic esophagitis (EoE) is an immune/antigen-mediated disease with an increasing incidence over the last decade. Clinicopathological remission can be achieved through different treatment options but often requires chronic therapy. To our knowledge, this is the first report of EoE wherein the patient (a 54-year-old man) achieved histological remission after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia. Overall, despite the success of EoE treatment in this case, further studies are needed to establish allogeneic HSCT as a curative option for EoE.

Racial and Ethnic Minorities With Acute Pancreatitis Live in Neighborhoods With Higher Social Vulnerability Scores.

OBJECTIVES: The primary objective was to determine differences in Social Vulnerability Index (SVI) scores among minorities (African-Americans and Hispanics) with acute pancreatitis (AP) compared with non-Hispanic whites (NHWs) with AP. The secondary objectives were to determine differences in diet, sulfidogenic bacteria gene copy numbers (gcn) and hydrogen sulfide (H2S) levels between the 2 groups. MATERIALS AND METHODS: Patients with AP were enrolled during hospitalization (n = 54). Patient residential addresses were geocoded, and the Centers for Disease Control and Prevention's SVI scores were appended. Dietary intake and serum H2S levels were determined. Microbial DNAs were isolated from stool, and gcn of sulfidogenic bacteria were determined. RESULTS: Minorities had higher SVI scores compared with NHWs ( P = 0.006). They also had lower consumption of beneficial nutrients such as omega-3 fatty acids [stearidonic ( P = 0.019), and eicosapentaenoic acid ( P = 0.042)], vitamin D ( P = 0.025), and protein from seafood ( P = 0.031). Lastly, minorities had higher pan-dissimilatory sulfite reductase A ( pan-dsrA ) gcn ( P = 0.033) but no significant differences in H2S levels ( P = 0.226). CONCLUSION: Minorities with AP have higher SVI compared with NHWs with AP. Higher SVI scores, lower consumption of beneficial nutrients, and increased gcn of pan-dsrA in minorities with AP suggest that neighborhood vulnerability could be contributing to AP inequities.

Acute Pancreatitis: Current Clinical Approaches, Molecular Pathophysiology, and Potential Therapeutics.

OBJECTIVE: Severe acute pancreatitis (SAP), pancreatic inflammation leading to multiorgan failure, is associated with high morbidity and mortality. There is a critical need to identify novel therapeutic strategies to improve clinical outcomes for SAP patients. MATERIALS AND METHODS: A comprehensive literature review was performed to identify current clinical strategies, known molecular pathophysiology, and potential therapeutic targets for SAP. RESULTS: Current clinical approaches focus on determining which patients will likely develop SAP. However, therapeutic options are limited to supportive care and fluid resuscitation. The application of a novel 5-cytokine panel accurately predicting disease outcomes in SAP suggests that molecular approaches will improve impact of future clinical trials in AP. CONCLUSIONS: Inflammatory outcomes in acute pancreatitis are driven by several unique molecular signals, which compound to promote both local and systemic inflammation. The identification of master cytokine regulators is critical to developing therapeutics, which reduce inflammation through several mechanisms.

Radiomics Boosts Deep Learning Model for IPMN Classification.

Intraductal Papillary Mucinous Neoplasm (IPMN) cysts are pre-malignant pancreas lesions, and they can progress into pancreatic cancer. Therefore, detecting and stratifying their risk level is of ultimate importance for effective treatment planning and disease control. However, this is a highly challenging task because of the diverse and irregular shape, texture, and size of the IPMN cysts as well as the pancreas. In this study, we propose a novel computer-aided diagnosis pipeline for IPMN risk classification from multi-contrast MRI scans. Our proposed analysis framework includes an efficient volumetric self-adapting segmentation strategy for pancreas delineation, followed by a newly designed deep learning-based classification scheme with a radiomics-based predictive approach. We test our proposed decision-fusion model in multi-center data sets of 246 multi-contrast MRI scans and obtain superior performance to the state of the art (SOTA) in this field. Our ablation studies demonstrate the significance of both radiomics and deep learning modules for achieving the new SOTA performance compared to international guidelines and published studies (81.9% vs 61.3% in accuracy). Our findings have important implications for clinical decision-making. In a series of rigorous experiments on multi-center data sets (246 MRI scans from five centers), we achieved unprecedented performance (81.9% accuracy). The code is available upon publication.

Diet, Gut Microbiome, and Their End Metabolites Associate With Acute Pancreatitis Risk.

INTRODUCTION: Diet and decreased gut microbiome diversity has been associated with acute pancreatitis (AP) risk. However, differences in dietary intake, gut microbiome, and their impact on microbial end metabolites have not been studied in AP. We aimed to determine differences in (i) dietary intake (ii) gut microbiome diversity and sulfidogenic bacterial abundance, and (iii) serum short-chain fatty acid (SCFA) and hydrogen sulfide (H 2 S) concentrations in AP and control subjects. METHODS: This case-control study recruited 54 AP and 46 control subjects during hospitalization. Clinical and diet data and stool and blood samples were collected. 16S rDNA sequencing was used to determine gut microbiome alpha diversity and composition. Serum SCFA and H 2 S levels were measured. Machine learning (ML) model was used to identify microbial targets associated with AP. RESULTS: AP patients had a decreased intake of vitamin D 3 , whole grains, fish, and beneficial eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids. AP patients also had lower gut microbiome diversity ( P = 0.021) and a higher abundance of sulfidogenic bacteria including Veillonella sp. and Haemophilus sp., which were associated with AP risk. Serum acetate and H 2 S concentrations were significantly higher in the AP group ( P < 0.001 and P = 0.043, respectively). ML model had 96% predictive ability to distinguish AP patients from controls. DISCUSSION: AP patients have decreased beneficial nutrient intake and gut microbiome diversity. An increased abundance of H 2 S-producing genera in the AP and SCFA-producing genera in the control group and predictive ability of ML model to distinguish AP patients indicates that diet, gut microbiota, and their end metabolites play a key role in AP.

Self-complementary AAV2.5-BMP2-coated femoral allografts mediated superior bone healing versus live autografts in mice with equivalent biomechanics to unfractured femur.

Structural allografts used for critical bone defects have limited osteogenic properties for biointegration. Although ex vivo tissue-engineered constructs expressing bone morphogenetic protein-2 (BMP2) have demonstrated efficacy in critical defect models, similar success has not been achieved with off-the-shelf acellular approaches, including allografts coated with freeze-dried single-stranded adeno-associated virus (ssAAV-BMP2). To see whether the self-complementary AAV serotype 2.5 vector (scAAV2.5-BMP2) could overcome this, we performed side-by-side comparisons in vitro and in the murine femoral allograft model. Although ssAAV-BMP2 was unable to induce BMP2 expression and differentiation of C3H10T1/2 cells in culture, scAAV2.5-BMP2 transduction led to dose-dependent BMP2 expression and alkaline phosphatase activity, and displayed a 25-fold increased transduction efficiency in vivo. After 6 weeks, the ssAAV-BMP2 coating failed to demonstrate any significant effects. However, all allografts coated with 10(10) scAAV2.5-BMP2 formed a new cortical shell that was indistinguishable to that formed by live autografts. Additionally, coated allografts experienced reduced resorption resulting in a threefold increase in graft bone volume versus autograft. This led to biomechanical superiority versus both allografts and autografts, and equivalent torsional rigidity to unfractured femur. Collectively, these results demonstrate that scAAV2.5-BMP2 coating overcomes the major limitations of structural allografts, which can be used to heal critical defects of any size.

Diagnosis and Management of Lemmel Syndrome: An Unusual Presentation and Literature Review.

Lemmel syndrome is a rare clinical entity characterized by the presence of a periampullary duodenal diverticulum resulting in compression and dilatation of the pancreatic and common bile ducts, accompanied by obstructive jaundice. Gastric outlet obstruction is not a known complication of this syndrome, and there are no standardized approaches to its treatment. We present the first case of Lemmel syndrome presenting as gastric outlet obstruction and provide the results of a systematic literature review.

The basis and design for time-restricted eating compared with daily calorie restriction for weight loss and colorectal cancer risk reduction trial (TRE-CRC trial).

OBJECTIVE: Approximately 42% of American adults are living with obesity, increasing their risk of colorectal cancer (CRC). Efficacious approaches to prevent and treat obesity may reduce CRC incidence. Daily calorie restriction (Cal-R) is the most common approach to treating obesity, yet clinically meaningful weight loss is elusive owing to waning adherence. Time-restricted eating (TRE) consists of consuming foods within a specified time frame, creating a natural calorie deficit. TRE in animals shows cancer protective effects. In humans, TRE is safe and acceptable among adults with obesity, producing ~3% to 5% weight loss and reductions in oxidative stress and insulin resistance. However, TRE has not been tested rigorously for CRC preventive effects. METHODS: The authors describe a 12-month randomized controlled trial of 8-hour TRE (ad libitum 12 PM-8 PM), Cal-R (25% restriction daily), or Control among 255 adults at increased risk for CRC and with obesity. RESULTS: Effects on the following will be examined: 1) body weight, body composition, and adherence; 2) circulating metabolic, inflammation, and oxidative stress biomarkers; 3) colonic mucosal gene expression profiles and tissue microenvironment; and 4) maintenance of benefits on body weight/composition and CRC risk markers. CONCLUSIONS: This study will examine efficacious lifestyle strategies to treat obesity and reduce CRC risk among individuals with obesity.

Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Type 1 Diabetes in Acute Pancreatitis Consortium.

ABSTRACT: Differences in methods for biospecimen collection, processing, and storage can yield considerable variability and error. Therefore, best practices for standard operating procedures are critical for successful discovery, development, and validation of disease biomarkers. Here, we describe standard operating procedures developed for biospecimen collection during the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) Study within the Type 1 Diabetes in Acute Pancreatitis Consortium. Notably, these protocols were developed using an integrative process based on prior consortium experience and with input from working groups with expertise in immunology, pancreatitis, and diabetes. Publication and adoption consistent biospecimen protocols will inform future studies and allow for better comparisons across different metabolic research efforts.

Recruitment and Retention Strategies for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: From the Type 1 Diabetes in Acute Pancreatitis Consortium.

ABSTRACT: 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 pre-emptive and detailed planning can help prospective, longitudinal studies focus on exocrine and endocrine complications of AP in accurately measuring outcomes. This article 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, which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study.

Design and Rationale for the Use of Magnetic Resonance Imaging Biomarkers to Predict Diabetes After Acute Pancreatitis in the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: From the Type 1 Diabetes in Acute Pancreatitis Consortium.

ABSTRACT: This core component of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) study will examine the hypothesis that advanced magnetic resonance imaging (MRI) techniques can reflect underlying pathophysiologic changes and provide imaging biomarkers that predict diabetes mellitus (DM) after acute pancreatitis (AP). A subset of participants in the DREAM study will enroll and undergo serial MRI examinations using a specific research protocol. The aim of the study is to differentiate at-risk individuals from those who remain euglycemic by identifying parenchymal features after AP. Performing longitudinal MRI will enable us to observe and understand the natural history of post-AP DM. We will compare MRI parameters obtained by interrogating tissue properties in euglycemic, prediabetic, and incident diabetes subjects and correlate them with metabolic, genetic, and immunological phenotypes. Differentiating imaging parameters will be combined to develop a quantitative composite risk score. This composite risk score will potentially have the ability to monitor the risk of DM in clinical practice or trials. We will use artificial intelligence, specifically deep learning, algorithms to optimize the predictive ability of MRI. In addition to the research MRI, the DREAM study will also correlate clinical computed tomography and MRI scans with DM development.

Rationale and Design for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: A Prospective Cohort Study From the Type 1 Diabetes in Acute Pancreatitis Consortium.

ABSTRACT: 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 after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) 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 after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.