Severe acute pancreatitis (SAP), marked by profound tissue inflammation within the pancreatic tissue, is an abrupt and intense inflammation of the pancreas. Chlorogenic acid (CGA) is one of the effective pharmacological ingredients components in JinHong Tablet (JHT). The role of CGA in protecting pancreas from severe injury in pancreatitis needs to be studied. The intervention with CGA led to a significant decline in serum amylase and lipase levels in rats with SAP, concurrently mitigating the pathological impairment within the pancreatic tissue. CGA effectively diminishes the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in SAP rats by inhibiting the activation of NF-κB and the NLRP3 inflammasome. Additionally, in AR42J cells, the application of CGA was found to reduce the inflammatory response induced by caerulein. Mechanically, CGA alleviates the inflammatory response in SAP models by activating the Nrf2/HO-1 pathway. Together, CGA reduces the inflammatory response of SAP by activating the Nrf2/HO-1 pathway, thus alleviating the development of SAP. Our results provide a basis for the treatment of SAP.

Pancreatic cancer (PC) manifests as a highly aggressive neoplastic growth, ranking as the fourth major contributor to cancer-related mortality in the United States. Despite sustained efforts, the incidence of PC is projected to rise, and the mortality rate has seen only a marginal reduction over time. A mere 15% of pancreatic cancer cases are deemed resectable upon presentation, explaining the notably low 5-year survival rate associated with this malignancy. Acute pancreatitis (AP) encompasses various degrees of inflammation in the pancreas, leading to diverse outcomes. While commonly associated with gallstone and alcohol use, it can serve as the initial presentation of PC in approximately 1% of cases. Our case series highlights two patients diagnosed with pancreatic cancer (PC) following an episode of acute pancreatitis (AP). It is not uncommon for PC to be preceded by AP, with up to 5.9% of PC cases in the United States presenting similarly.

tRNA-derived small RNAs (tsRNAs), encompassing tRNA fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs), represent a category of non-coding small RNAs (sncRNAs) that are increasingly recognized for their diverse biological functions. These functions include gene silencing, ribosome biogenesis, retrotransposition, and epigenetics. tsRNAs have been identified as key players in the progression of various tumors, yet their specific roles in pancreatic cancer (PC) and acute pancreatitis (AP) remain largely unexplored. Pancreatic cancer, particularly pancreatic ductal adenocarcinoma, is notorious for its high mortality rate and extremely low patient survival rate, primarily due to challenges in early diagnosis. Similarly, acute pancreatitis is a complex and significant disease. This article reviews the roles of 18 tsRNAs in PC and AP, focusing on their mechanisms of action and potential clinical applications in these two diseases. These tsRNAs influence the progression of pancreatic cancer and acute pancreatitis by modulating various pathways, including ZBP1/NLRP3, Hippo, PI3K/AKT, glycolysis/gluconeogenesis, and Wnt signaling. Notably, the dysregulation of tsRNAs is closely linked to critical clinical factors in pancreatic cancer and acute pancreatitis, such as lymph node metastasis, tumor-node-metastasis (TNM) stage, overall survival (OS), and disease-free survival (DFS). This article not only elucidates the mechanisms by which tsRNAs affect pancreatic cancer and acute pancreatitis but also explores their potential as biomarkers and therapeutic targets for pancreatic cancer. The insights provided here offer valuable references for future research, highlighting the importance of tsRNAs in the diagnosis and treatment of these challenging diseases.

Acute pancreatitis is a commonly encountered pathology in the emergency department. We presented a clinical review summarizing the contemporary emergency medicine approach to managing acute pancreatitis. Although the diagnostic criteria for acute pancreatitis are straightforward, it has many possible causes, several treatment options, and both short- and long-term sequelae. We discussed diagnostic, intervention, and disposition considerations relevant to emergency clinicians and considered risk assessment using available clinical decision tools. We also discussed changes to traditional treatments and ongoing investigational therapies, including steroids, monoclonal antibodies, and calcium release-activated calcium channel inhibitors.

Acute pancreatitis (AP) is a common disease of acute abdominal pain, the incidence of which is increasing annually, but its pathogenesis remains incompletely understood.

Gene expression profiles of AP were obtained from the Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes (DEGs) and perform functional analysis. The diagnostic value of HLA-DR-related genes was assessed by receiver operating characteristic (ROC) curves. Monocyte infiltration abundance in AP and normal groups was analyzed by Cibersort method, and the correlation between HLA-DR-related genes and monocyte abundance was analyzed. The modules highly correlated with HLA-DR-related genes were clarified by WGCNA modeling, and the core genes regulating HLA-DR were obtained by using LASSO regression. Finally, potential drugs targeting the above genes were analyzed by Enrichr database.

A Total of 3 HLA-DR-related genes (HLA-DRA, HLA-DRB1, and HLA-DRB5) were identified, which were negatively correlated with the severity of AP and had excellent disease diagnostic value (AUC = 0.761, 0.761, and 0.718), were were positively correlated with monocyte abundance. We identified 110 genes that positively regulate HLA-DR and 130 genes that negatively regulate HLA-DR. LASSO regression identified UCP2, GK, and SAMHD1 as the core nodes of the regulated genes. Compared with the normal group, UCP2 and SAMHD1 were reduced in AP, and the opposite was true for GK, and SAMHD1 had better sensitivity and specificity in diagnosing AP. Drug sensitivity analysis predicted 12 drugs acting on HLA-DRA, HLA-DRB1, and HLA-DRB5 and 8 drugs acting on UCP2, GK, and SAMHD1.

We identified 3 HLA-DR-related genes (HLA-DRA, HLA-DRB1, and HLA-DRB5) and 3 coregulatory nodes (UCP2, GK, and SAMHD1), which were associated with AP severity and monocyte abundance. Based on these genes, we predicted 20 potential therapeutic agents for AP.

After an aetiological (first-line) workup, the cause of acute pancreatitis remains unidentified in a significant proportion of cases, a condition known as idiopathic acute pancreatitis (IAP).

Retrospective cohort study involving patients with presumed IAP referred for second-line aetiological workup. The completion of first-line aetiological evaluations was assessed upon referral, and the diagnostic outcomes of second-line investigations were evaluated. Over a one-year follow-up period, we documented acute pancreatitis recurrence and patient mortality. Recurrence risk was analysed using an age-adjusted Cox regression model, stratified by treatable versus non-treatable aetiologies.

We identified 161 patients with presumed IAP, among whom 81 (50%) had recurrent acute pancreatitis. In total, 115 patients (71%) had a complete first-line aetiological workup. The overall diagnostic yield of the second-line aetiological workup was 25% (95% confidence interval [CI] 18-32%). Among second-line tests, the highest diagnostic yield was found for endoscopic ultrasound (34%, 95% CI 20-50%) and genetic testing (37%, 95% CI 22-53%). The most frequent aetiologies identified were biliary pancreatitis (16 patients [10%]) and pancreatitis with a genetic mutation (15 patients [9%]). Neoplasia was identified in two patients. A treatable aetiology was associated with a numerically reduced pancreatitis recurrence risk (Hazard Ratio 0.50, 95% CI 0.07-3.85, p = 0.51). No patient died during the follow-up period.

A second-line aetiological workup can identify the aetiology in 25% of patients with presumed IAP. The most frequent aetiologies are biliary pancreatitis and pancreatitis with a genetic mutation.

The precise incidence of immune-related adverse events (irAEs) remains unclear. This pharmacovigilance study investigated acute pancreatitis (AP) associated with immune checkpoint inhibitors (ICIs) using real-world data from the FDA Adverse Event Reporting System (FAERS).

Disproportionality analysis employing reporting odds ratios (RORs) was conducted to detect AP signals in ICI-treated patients compared to the entire FAERS database.

A total of 152,042 individual patients were included in the dataset from which we identified a cohort of 921 acute pancreatitis adverse events (AEs). The severe outcome of acute pancreatitis was death, with a rate of 13.6% (125/921). Immune checkpoint inhibitor (ICI)-related acute pancreatitis AEs were classified into two categories (pancreatitis and immune-mediated pancreatitis) based on the type of adverse event observed. ICI treatments were significantly correlated with the risk of ICIs-induced acute pancreatitis (AP) but varied among different drugs. The median time to AP onset was 57 days, with events occurring throughout the first year post-ICI initiation.

Our findings provide an enhanced understanding of potential acute pancreatitis related adverse events and provide actionable insights for the early detection and management of ICI related pancreatic adverse events.

Biliary strictures can be secondary to a gamut of etiologies, most of which are malignant and the remaining related to a host of benign causes, including pancreatitis. Pancreatitis related benign biliary strictures (BBS) primarily involve the distal common bile duct (CBD) and can be seen in acute and chronic pancreatitis as well as their other forms, including necrotizing, groove, and autoimmune pancreatitis. Patients with pancreatitis related BBS present along a wide clinical spectrum that spans from an asymptomatic state to biliary obstruction, which not uncommonly facilitates additional workup for malignancy and endoscopic evaluation and treatment. Furthermore, the location and appearance of these strictures lends itself to various imitating benign and malignant etiologies. In this article, we will discuss the pathophysiology and clinicoradiologic features of pancreatitis related BBS while providing a review of an approach to their management focusing on endoscopic techniques.

Alcohol significantly contributes to pancreatitis, causing high global mortality and health burden. This study examines trends in alcohol-attributable pancreatitis (AAP) from 1990 to 2021 using Global Burden of Disease (GBD) 2021 data, focusing on demographic, temporal, and regional variations to inform policymaking.

AAP-related deaths and disability-adjusted life years (DALYs) were analyzed across 204 countries from 1990 to 2021, stratified by Sociodemographic Index (SDI), gender, and age groups. An age-period-cohort model assessed age-standardized death rates (ASDR), and decomposition analysis quantified impacts of population growth, aging, and epidemiological changes.

AAP-related DALYs rose from 401,700 in 1990 to 699,300 in 2021, though ASDR and ASMR showed declines globally. Burden increased notably in low and lower-middle SDI regions, especially among those under 40, while high SDI regions achieved better control. Males faced a disproportionately high burden due to alcohol consumption patterns, although some regions saw rising female burdens. Low-SDI areas suffered from limited healthcare, increasing alcohol use, and weak policies, with younger populations contributing significantly to rising burdens. Projections estimate 1.146 million DALYs annually by 2050, with males comprising over 90%. A GBD-AAP visualization platform was developed to present burden data and trends.

AAP exhibits significant regional and gender disparities. Targeted measures, including alcohol regulation, resource allocation, and public health education, are critical in low-SDI regions and among young males to mitigate AAP burden. The GBD-AAP platform offers valuable tool for targeted interventions.

Acute pancreatitis can lead to systemic inflammation and multiple organ damage. Increased endothelial permeability is a hallmark of systemic inflammation. Several studies have demonstrated that cold-inducible RNA-binding protein (CIRP) functions as a proinflammatory factor in various diseases. However, its role in endothelial barrier dysfunction during acute pancreatitis remains unknown. To study this, acute pancreatitis was induced by two hourly intraperitoneal injections of 4.0 g/kg L-arginine in wild-type (WT) or CIRP knockout mice. Our results showed that CIRP levels in the pancreas, small intestine, lung, and liver were upregulated at 72 h after the induction of acute pancreatitis in WT mice. CIRP deficiency significantly attenuated tissue injury, edema, and extravasation of Evans blue in the pancreas, small intestine, lung, and liver at 72 h after L-arginine injection. Administration of C23, a specific antagonist of CIRP, at 2 h after the last injection of L-arginine also produced similar protective effects as CIRP knockout in mice. In vitro studies showed that recombinant CIRP caused a significant reduction in transcellular electric resistance in HUVEC monolayers. Immunocytochemical analysis of endothelial cells exposed to CIRP revealed an increased formation of actin stress fibers. VE-cadherin and β-catenin staining showed intercellular gaps were formed in CIRP-stimulated cells. Western blot analysis showed that CIRP induced SRC phosphorylation at TYR416. Exposure to the SRC inhibitor PP2 reduced CIRP-induced endothelial barrier dysfunction in HUVEC monolayers. In conclusion, blocking CIRP mitigates acute pancreatitis-induced multiple organ damage by alleviating endothelial hyperpermeability. Targeting CIRP may be a potential therapeutic option for acute pancreatitis.

Pancreatitis is a prominent and severe type of inflammatory disorder that has grabbed a lot of scientific and clinical interest to prevent its onset. It should be detected early to avoid the development of serious complications, which occur due to long-term damage to the pancreas. The accurate measurement of biomarkers that are released from the pancreas during inflammation is essential for the detection and early treatment of patients with severe acute and chronic pancreatitis, but this is sub-optimally performed in clinically relevant practices, mainly due to the complexity of the procedure and the cost of the treatment. Clinically available tests for the early detection of pancreatitis are often time-consuming. The early detection of pancreatitis also relates to disorders of the exocrine pancreas, such as cystic fibrosis in the hereditary form and cystic fibrosis-like syndrome in the acquired form of pancreatitis, which are genetic disorders with symptoms that can be correlated with the overexpression of specific markers such as creatinine in biological fluids like urine. In this review, we studied how to develop a minimally invasive system using hydrogel-based biosensors, which are highly absorbent and biocompatible polymers that can respond to specific stimuli such as enzymes, pH, temperature, or the presence of biomarkers. These biosensors are helpful for real-time health monitoring and medical diagnostics since they translate biological reactions into quantifiable data. This paper also sheds light on the possible use of Ayurvedic formulations along with hydrogels as a treatment strategy. These analytical devices can be used to enhance the early detection of severe pancreatitis in real time.

Acute pancreatitis (AP) represents one of the most common reasons for hospital admission and intensive care treatment in internal medicine. The incidence of AP is increasing, posing significant financial burden on healthcare systems due to the necessity for frequent medical interventions. Severe acute pancreatitis (SAP) is a potentially life-threatening condition with substantial morbidity and mortality. The management of SAP requires prolonged hospitalization and the expertise of a multidisciplinary team, comprising emergency physicians, intensivists, internists, gastroenterologists, visceral surgeons, and experts in nutrition, infectious disease, endoscopy, as well as diagnostic and interventional radiology. Effective management and beneficial patient outcomes depend on continuous interdisciplinary collaboration. This review synthesizes recent evidence guiding the practical management of SAP, with a particular focus on emergency and intensive care settings. Both established as well as new diagnostic and therapeutic paradigms are highlighted, including workup, risk stratification, fluid management, analgesia, nutrition, organ support, imaging modalities and their timing, along with anti-infective strategies. Furthermore, the review explores interventions for local and vascular complications of SAP, with particular attention to the indications, timing and selection between endoscopic (both endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS)), percutaneous and surgical approaches. Similarly, the management of biliary AP due to obstructive gallstones, including the imaging, timing of ERCP and cholecystectomy, are discussed. By integrating new evidence with relevant guidance for everyday clinical practice, this review aims to enhance the interdisciplinary approach essential for improving outcomes in SAP management.

Acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis are recognized as a continuum of pancreatic diseases. Recurrence increases the risk of progression to chronic pancreatitis. The aim of this study was to search for clinical features that may promote the progression of chronic pancreatitis in patients with recurrent acute pancreatitis.

We retrospectively reviewed patients with recurrent acute pancreatitis from Medical Information Mart for Intensive Care-IV database. They were divided into a training cohort and a validation cohort. A nomogram was constructed based on clinical features during the second hospitalization. The discrimination and calibration of the nomogram were evaluated using the concordance index, area under the time-dependent receiver operating characteristic curve, and calibration plots.

A total of 432 recurrent acute pancreatitis patients were evaluated, of which 93 (21.53%) were diagnosed with chronic pancreatitis later. Age, biliary pancreatitis, admission interval, alcohol dependence, lipase, and platelet were selected. The concordance index was 0.717 (95% confidence interval: 0.691-0.743) for the training cohort and 0.718 (95% confidence interval: 0.662-0.774) for the validation cohort. The area under the time-dependent receiver operating characteristic curve was >0.7 over 1000 days.

A nomogram was developed and validated to evaluate the transition from recurrent acute pancreatitis to chronic pancreatitis.

This study developed and validated a stacked ensemble machine learning model to predict the risk of acute kidney injury in patients with acute pancreatitis complicated by sepsis.

A retrospective study based on patient data from public databases.

This study analysed 1295 patients with acute pancreatitis complicated by septicaemia from the US Intensive Care Database.

From the MIMIC database, data of patients with acute pancreatitis and sepsis were obtained to construct machine learning models, which were internally and externally validated. The Boruta algorithm was used to select variables. Then, eight machine learning algorithms were used to construct prediction models for acute kidney injury (AKI) occurrence in intensive care unit (ICU) patients. A new stacked ensemble model was developed using the Stacking ensemble method. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), precision-recall (PR) curve, accuracy, recall and F1 score. The Shapley additive explanation (SHAP) method was used to explain the models.

AKI in patients with acute pancreatitis complicated by sepsis.

The final study included 1295 patients with acute pancreatitis complicated by sepsis, among whom 893 cases (68.9%) developed acute kidney injury. We established eight base models, including Logit, SVM, CatBoost, RF, XGBoost, LightGBM, AdaBoost and MLP, as well as a stacked ensemble model called Multimodel. Among all models, Multimodel had an AUC value of 0.853 (95% CI: 0.792 to 0.896) in the internal validation dataset and 0.802 (95% CI: 0.732 to 0.861) in the external validation dataset. This model demonstrated the best predictive performance in terms of discrimination and clinical application.

The stack ensemble model developed by us achieved AUC values of 0.853 and 0.802 in internal and external validation cohorts respectively and also demonstrated excellent performance in other metrics. It serves as a reliable tool for predicting AKI in patients with acute pancreatitis complicated by sepsis.

To study the mechanism of calcitonin gene related peptide(CGRP) protecting acute pancreatitis based on metabolomics. 24 adult male rats were randomly divided into control group (Con), acute pancreatitis model group (AP), CGRP treatment group (CGRP + AP, abbreviated as CGRP) and CGRP antagonist(CGRP(8-37)) pretreatment group (preCGRP(8-37) + AP, abbreviated as CGRP37), with 6 rats in each group. After different interventions, pancreases of rats in each group were collected for pathological analysis, and serum was collected for metabolomics analysis. Pathological examination of the pancreas suggested that the inflammation of pancreatitis in AP group was significant, the inflammation of pancreatitis in CGRP group was significantly reduced, and the pancreatitis in CGRP37 group was aggravated. Metabolomics of rat serum suggested that the differences in metabolites in each group were mainly related to amino acid metabolism, coenzyme/vitamin metabolism, carbohydrate metabolism, lipid metabolism, digestive system and other metabolic pathways. According to the trend of metabolite changes, we found 6 differential metabolites that were significantly correlated with CGRP intervention, including L-Valine, 5-Aminopentanoic acid, 4-oxo-L-proline, L-glutamine, L-proline, and Ornithine, all of which were related to amino acid metabolism. CGRP can effectively protect acute pancreatitis, possibly by regulating amino acid metabolism to alleviate acute pancreatitis.

Pancreatic cancer (PC) is a malignancy of gastrointestinal tract threatening the life of people around the world. In spite of the advances in the treatment of PC, the overall survival of this disease in advanced stage is less than 12%. Moreover, PC cells have aggressive behaviour in proliferation and metastasis as well as capable of developing therapy resistance. Therefore, highlighting the underlying molecular mechanisms in PC pathogenesis can provide new insights for its treatment. In the present review, inflammation and related pathways as well as role of gut microbiome in the regulation of PC pathogenesis are highlighted. The various kinds of interleukins and chemokines are able to regulate angiogenesis, metastasis, proliferation, inflammation and therapy resistance in PC cells. Furthermore, a number of molecular pathways including NF-κB, TLRs and TGF-β demonstrate dysregulation in PC aggravating inflammation and tumorigenesis. Therapeutic regulation of these pathways can reverse inflammation and progression of PC. Both chronic and acute pancreatitis have been shown to be risk factors in the development of PC, further highlighting the role of inflammation. Finally, the composition of gut microbiota can be a risk factor for PC development through affecting pathways such as NF-κB to mediate inflammation.

Although often overlooked, drug-induced pancreatitis is a frequent cause of pancreatitis. Pancreatic drug toxicity is defined according to the classification by Mallory et al. and Trivedi et al. Isotretinoin is only classified as possibly toxic to the pancreas (class 3). We report the first case of recurrence of pancreatitis after rechallenge, which argues for a modification of the classification of drug-induced pancreatitis.

We present here the case of a 20-year-old Belgian man who suffered several episodes of acute pancreatitis for which no etiology could be identified despite an exhaustive assessment. Eventually, as a precaution, isotretinoin was discontinued and there was no recurrence until it was reintroduced.

This is the 25th case described in the literature, but the first with a positive rechallenge on two occasions. This case therefore implies that isotretinoin should definitely be considered a class 1 toxic drug for the pancreas and should be incriminated in acute pancreatitis in patients treated with this drug.

Macrophage infiltration and activation is a critical step during acute pancreatitis (AP). NLRP3 inflammasomes in macrophages plays a critical role in mediating pancreatic inflammatory responses. Qing-Yi Decoction(QYD)has been used for many years in clinical practice of Nankai Hospital combined with traditional Chinese and western medicine treatment of acute pancreatitis. Although QYD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects. Here, we elucidate the therapeutic effects of QYD against acute pancreatitis and reveal its mechanism of action.

The main components of QYD were identified using UHPLC-Q-Orbitrap MS. Network pharmacology was employed to predict potential therapeutic targets and their mechanisms of action. C57BL/6 mice were randomly divided into control group, model group, low, medium and high dose (6, 12, 24 g/kg) QYD groups, with 10 mice in each group. The therapeutic effect of QYD on cerulein-induced acute pancreatitis. (CER-AP) was evaluated by histopathological score, immunohistochemistry, serum amylase and cytokines detection by ELISA. The protein expressions of MyD88/NF-κB/NLRP3 signaling pathway were detected by Western blotting. Along with molecular docking of key bioactive compounds and targets, RAW264.7 cells stimulated with 1μg/ml LPS is used to screen components with more potent effects on target proteins. AR42 J cells were stimulated with 100 nM dexamethasone (dexa) combined with 10 nM cerulein (CN) as s a cell-culture model of acute pancreatitis. Inhibitory effects of the main chemical composition Wogonoside on NLRP3 inflammasomes were analyzed by qRT-PCR and Western blots.

Using UHPLC-Q-Orbitrap MS, 217 compounds were identified from QYD, including Wogonoside, Catechins, Rhein, etc. A visualization network of QYD-compounds-key targets-pathways-AP show that QYD may modulate PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Ras signaling pathway and Apoptosis signaling pathway by targeting TNF, IL1β, AKT1, TP53 and STAT3 exerting a therapeutic effect on AP. QYD administration effectively mitigated CER-induced cytokine storm, pancreas edema and serum amylase. QYD (12 mg/kg) showed better effect. The protein expression levels of MyD88, NF-κB, NLRP3, Caspase-1 and GSDMD in pancreatic tissue were significantly decreased. Through molecular docking and LPS-RAW264.7 inflammation model, the selected Wogonoside significantly decreased IL-1β mRNA. The expression levels of NLRP3/Caspase-1/GSDMD pathway-related proteins were also decreased on AR42J-AP.

The results of network pharmacology indicate that QYD can inhibit AP through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that QYD can reduce AP by inhibiting NLRP3 inflammasomes, additionally, it should be noted that 12mg/kg was a relatively superior dose. One of the main chemical compositions Wogonoside regulated NLRP3 inflammasome activation to protect against AP. This study is the first to verify the intrinsic molecular mechanism of QYD in treating AP by combining network pharmacology and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.

Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, often resulting in self-digestion, edema, hemorrhage, and even necrosis of pancreatic tissue. When AP progresses to severe acute pancreatitis (SAP), it often causes multi-organ damage, leading to a high mortality rate. However, the molecular mechanisms underlying SAP-mediated organ damage remain unclear. This study aims to systematically mine SAP data from public databases and combine experimental validation to identify key molecules involved in multi-organ damage caused by SAP. Retrieve transcriptomic data of mice pancreatic tissue for AP, lung and liver tissue for SAP, and corresponding normal tissue from the Gene Expression Omnibus (GEO) database. Conduct gene differential analysis using Limma and DEseq2 methods. Perform enrichment analysis using the clusterProfiler package in R software. Score immune cells and immune status in various organs using single-sample gene set enrichment analysis (ssGSEA). Evaluate mRNA expression levels of core genes using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Validate serum amylase, TNF-α, IL-1β, and IL-6 levels in peripheral blood using enzyme-linked immunosorbent assay (ELISA), and detect the formation of neutrophil extracellular traps (NETs) in mice pancreatic, liver, and lung tissues using immunofluorescence. Differential analysis reveals that 46 genes exhibit expression dysregulation in mice pancreatic tissue for AP, liver and lung tissue for SAP, as well as peripheral blood in humans. Functional enrichment analysis indicates that these genes are primarily associated with neutrophil-related biological processes. ROC curve analysis indicates that 12 neutrophil-related genes have diagnostic potential for SAP. Immune infiltration analysis reveals high neutrophil infiltration in various organs affected by SAP. Single-cell sequencing analysis shows that these genes are predominantly expressed in neutrophils and macrophages. FPR1, ITGAM, and C5AR1 are identified as key genes involved in the formation of NETs and activation of neutrophils. qPCR and IHC results demonstrate upregulation of FPR1, ITGAM, and C5AR1 expression in pancreatic, liver, and lung tissues of mice with SAP. Immunofluorescence staining shows increased levels of neutrophils and NETs in SAP mice. Inhibition of NETs formation can alleviate the severity of SAP as well as the levels of inflammation in the liver and lung tissues. This study identified key genes involved in the formation of NETs, namely FPR1, ITGAM, and C5AR1, which are upregulated during multi-organ damage in SAP. Inhibition of NETs release effectively reduces the systemic inflammatory response and liver-lung damage in SAP. This research provides new therapeutic targets for the multi-organ damage associated with SAP.

Acute pancreatitis (AP) and chronic pancreatitis (CP) have high incidences and poor prognoses. The early screening of at-risk populations still awaits further study. The limitation was mainly based on observational studies, with limited sample size and the presence of confounding factors. This study used a 2-sample Mendelian randomization (MR) analysis based on publicly available data from genome-wide association studies to reveal the causal effect of gut microbiota and metabolites on pancreatitis.

This study collected summary statistics on gut microbiota, metabolites, AP, and CP. A 2-sample MR analysis was performed using MR-Egger, inverse variance-weighted, MR Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median.

The 2-sample MR showed that only Eubacterium coprostanoligenes was an independent protective factor for AP among all gut microbiota, and the other microbiota were not significant for pancreatitis. Unsaturated fatty acids in metabolites are protective factors for both AP (odds ratio [OR], 0.730; 95% CI, 0.593-0.899; P = .003) and CP (OR, 0.660; 95% CI, 0.457-0.916; P = .013). Furthermore, carnitine was a protective factor CP, and glucose was an independent risk factor for CP.

This study provides potential evidence of the causal role of gut microbiota and metabolites on pancreatitis, which may be conducive for designing microbiome and metabolite interventions on AP or CP in the future.

The IL-2 family, consisting of IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, is a key regulator of the immune response. As an important endocrine and digestive organ, the function of the pancreas is regulated by the immune system. Studies have shown that each cytokine of the IL-2 family influences the occurrence and development of pancreatic diseases by participating in the regulation of the immune system. In this paper, we review the structural and functional characteristics of IL-2 family members, focus on their molecular mechanisms in pancreatic diseases including acute pancreatitis, chronic pancreatitis and pancreatic cancer, and highlight the importance of the related proteins in the regulation of immune response and disease progression, which will provide valuable insights for new biomarkers in pancreatic diseases, early diagnosis of the diseases, assessment of the disease severity, and development of new therapeutic regimens. The insights of the study are summarized in the following sections.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and non-alcoholic fatty pancreatic disease (NAFPD) are metabolic diseases with rising incidence. Fatty infiltration may lead to dysfunction of the liver and pancreatic tissues. This study aims to quantify liver and pancreatic fat fractions and examine their correlation with disease severity in acute pancreatitis patients.

The severity of acute pancreatitis was assessed using the revised Atlanta classification (RAC), computed tomography severity index (CTSI), and modified CTSI (mCTSI). Proton density fat fraction (PDFF) levels of the liver and pancreas were measured via IDEAL MRI. Patients were categorized into biliary and non-biliary pancreatitis groups. Correlations between PDFF levels and the RAC, CTSI, and mCTSI scores were analyzed.

A total of 127 patients were included, with MASLD present in 40.9% and NAFPD in 30%. Liver PDFF values were significantly higher in non-biliary pancreatitis (p = 0.040). Patients with MASLD exhibited higher CTSI and mCTSI scores (p = 0.009, p = 0.033, respectively). No significant differences were observed in severity scales between patients with and without NAFPD. Liver PDFF was positively correlated with CTSI and mCTSI scores in biliary pancreatitis. ROC analysis identified a liver PDFF > 3.9% (p = 0.002) and pancreatic corpus PDFF > 12.1% (0.028) as diagnostic markers for severe pancreatitis. In addition, a liver PDFF < 4.5% (p = 0.042) was an indicator for biliary pancreatitis.

MASLD is associated with increased severity in acute pancreatitis. IDEAL MRI-derived PDFF levels of the liver and pancreas show potential in predicting severe acute pancreatitis and distinguishing between biliary and non-biliary etiologies.

Acute pancreatitis (AP) is a disease characterized by an acute inflammatory response in the pancreas. This is caused by the abnormal activation of pancreatic enzymes by a variety of etiologic factors, which results in a localized inflammatory response. The symptoms of this disease include abdominal pain, nausea and vomiting and fever. These symptoms are induced by a hyperinflammatory response and oxidative stress. In recent years, research has focused on developing anti-inflammatory and antioxidative therapies for the treatment of acute pancreatitis (AP). However, there are still limitations to this approach, including poor drug stability, low bioavailability and a short half-life. The advent of nanotechnology has opened up a novel avenue for the management of acute pancreatitis (AP). Nanomaterials can serve as an efficacious vehicle for conventional pharmaceuticals, enhancing their targeting ability, improving bioavailability and prolonging their half-life. Moreover, they can also exert a direct therapeutic effect. This review begins by introducing the general situation of acute pancreatitis (AP). It then discusses the pathogenesis of acute pancreatitis (AP) and the current status of treatment. Finally, it considers the literature related to the treatment of acute pancreatitis (AP) by nanomaterials. The objective of this study is to provide a comprehensive review of the existing literature on the use of nanomaterials in the treatment of acute pancreatitis (AP). In particular, the changes in inflammatory markers and therapeutic outcomes following the administration of nanomaterials are examined. This is done with the intention of offering insights that can inform subsequent research and facilitate the clinical application of nanomaterials in the management of acute pancreatitis (AP).

Acute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP.

Liver-targeted lipid nanoparticles (LNP)-mRNA formulations encoding FGF21, APOA1, and a chimeric APOA1-FGF21, were first tested for protein expression and bioavailability in vitro and in mice fed a high-fat diet. Efficacy studies were performed in the caerulein-induced AP (Cer-AP) model, and a new AP model combining ethanol feeding with ethanol binge plus palmitoleic acid administration, the EtOH/POA-AP model. A single dose of the APOA1, FGF21, and APOA1-FGF21 LNP-mRNAs formulations was administered in both models. Serum levels of pancreatic lipase (LIPC), amylase (AMYL), and aspartate aminotransferase (AST), along with pancreatic tissue analyses using two histopathological scores were performed to evaluate treatment effects.

In vitro studies demonstrated the translation and secretion of APOA1, FGF21, and APOA1-FGF21 proteins encoded by the LNP-mRNAs. In vivo, LNP-mRNA administration increased serum levels of the respective proteins in metabolically impaired (i.e. high fat diet-fed) mice. In the Cer-AP model, serum markers of pancreatic injury were similarly reduced when mice were treated with APOA1, FGF21, and APOA1-FGF21 LNP-mRNA, and this effect was also observed in the histopathological analyses. The EtOH/POA-AP model was more aggressive than the Cer-AP model. FGF21 and APOA1-FGF21 LNP-mRNAs were protective according to LIPC and AMYL serum levels, while APOA1 LNP-mRNA had little effect. On the other hand, histological improvements were more evident in mice receiving APOA1 LNP-mRNA. In the EtOH/POA-AP model, FGF21 and APOA1-FGF21 LNP-mRNAs reduced serum AST levels, indicating hepatoprotective activity.

This proof-of-concept study demonstrates the potential of mRNA-based therapies delivering FGF21 and APOA1 in experimental AP. While individual treatments effectively reduced pancreatic injury, the APOA1-FGF21 fusion molecule did not exhibit superior activity. Liver-targeted LNP-mRNA administration may offer a promising approach for treating AP, leveraging endogenous production pathways for therapeutic proteins. Further research is warranted to elucidate the mechanisms underlying their therapeutic efficacy and optimize treatment regimens for clinical translation.

Background and Objectives: During acute pancreatitis, leakage of pancreatic enzymes into the gland results in autolysis of the pancreas. The lungs are also involved in this process. This study aimed to investigate the therapeutic effects of esomeprazole on damaged pancreatic tissue and affected lung tissue in rats with acute pancreatitis. Materials and Methods: The 24 Wistar-Albino male rats were divided into three groups: Control group (2 mL 0.9% saline solution was given intraperitoneally, n = 8); PCT group (acute pancreatitis was induced and then 2 mL 0.9% saline solution was administered intraperitoneally, n = 8); ESM group (acute pancreatitis was induced and then 10 mg/kg esomeprazole was administered intraperitoneally, n = 8). Then, the lungs and pancreas were completely removed, and blood samples were taken from all rats for histopathological and biochemical examination. Results: Pancreatic edema, vacuolization, necrosis, and inflammation in the PCT group were higher than in the control and ESM groups. Alveolar edema, alveolar distension, alveolar PMNL infiltration, and alveolar wall thickness in the PCT group were higher than in the control and ESM groups. Furthermore, IL-β (F = 40.137, p < 0.001), TNF-α (F = 40.132, p < 0.001), MIP-2 (X2 = 19.245, p < 0.001), ICAM-1 (F = 14.312, p < 0.001), NO (F = 25.873, p < 0. 001), amylase (F = 30.333, p < 0.001), and lipase (X2 = 16.141, p < 0.001) values measured in serum were different among groups. Pairwise group comparisons revealed that IL-β, TNF-α, MIP-2, and amylase levels in the ESM group were lower than in the PCT group (p < 0.05). Conclusions: Esomeprazole could be recommended in clinical practice during acute pancreatitis treatment due to its therapeutic effects on damaged pancreatic and lung tissues secondary to pancreatitis in rats.

The p21-activated kinases (PAKs) are a conserved family of serine/threonine protein kinases, which are effectors for the Rho family GTPases, namely, Rac/Cdc42. PAKs are divided into two groups: group I (PAK1-3) and group II (PAK4-6). Both groups of PAKs have been well studied in apoptosis, protein synthesis, glucose homeostasis, growth (proliferation and survival) and cytoskeletal regulation, as well as in cell motility, proliferation and cycle control. However, little is known about the role of PAKs in the secretory tissues, including in exocrine tissue, such as the exocrine pancreas (except for islet function and pancreatic cancer growth). Recent studies have provided insights supporting the importance of PAKs in exocrine pancreas. This review summarizes the recent insights into the importance of PAKs in the exocrine pancreas by reviewing their presence and activation; the ability of GI hormones/neurotransmitters/GFs/post-receptor activators to activate them; the kinetics of their activation; the participation of exocrine-tissue PAKs in activating the main growth-signaling cascade; their roles in the stimulation of enzyme secretion; finally, their roles in pancreatitis. These insights suggest that PAKs could be more important in exocrine/secretory tissues than currently appreciated and that their roles should be explored in more detail in the future.

This study aims to analyzing scientific publications related to necrotizing pancreatitis and its mortality, identifying key areas and trends, and determining the leading research institutions, authors, countries, and journals actively working in this field.

The Web of Science and Scopus databases were searched for articles on NP published between January 1, 2013, and April 22, 2024. Articles published before 2013, conference abstracts, and case reports were excluded. The articles were assessed based on various metrics, including the number of citations, publication dates, countries of origin, institutions, journals, and authors.

A total of 929 articles were identified, of which 251 were deemed suitable for analysis after duplicates were removed. China contributed the most articles, followed by the United States and India. The most frequent publications appeared in specialized journals such as "Pancreatology" and "Journal of Gastrointestinal Surgery." The primary research institutions were universities and medical centers. The highest-impact articles focused on minimally invasive treatment methods for NP. There has been a growing body of research in NP over the past decade, particularly in China and the United States.

Despite advancements in medical science, the mortality rate associated with pancreatic necrosis remains high. This highlights the continued challenge in effectively addressing complications of acute pancreatitis. Researchers worldwide are actively exploring alternative therapeutic approaches to mitigate these complications and improve patient outcomes.

Oxidative stress (OS) injury is pivotal in acute pancreatitis (AP) pathogenesis, contributing to inflammatory cascades. Irisin, a ubiquitous cytokine, exhibits antioxidant properties. However, the role of irisin in AP remains inconclusive. Our study aims to elucidate irisin expression in AP patients and investigate its mechanism of action to propose a novel treatment strategy for AP. Serum irisin levels in 65 AP patients were quantified using an enzyme-linked immunosorbent assay and correlated with disease severity scores. Core genes implicated in AP-related oxidative stress were identified and screened via bioinformatics analysis. The therapeutic efficacy of irisin in AP was confirmed using a murine cerulein-induced AP model. The intrinsic mechanism of irisin's antioxidative stress action was investigated and verified in pancreatic AR42J cells (Supplementary Fig. 1). Common targets shared by irisin and AP were further validated using a molecular docking model which was constructed for virtual docking analysis. This study investigated alterations in redox status in AP and found a significant reduction in serum irisin levels, correlating inversely with AP severity. In a murine AP model, we showed that irisin triggers an antioxidative stress program via the KEAP1 gene; this process helps reestablish redox balance by decreasing the buildup of reactive oxygen species (ROS) and suppressing the secretion of inflammatory mediators within pancreatic tissues Notably, increased KEAP1 expression counteracted the antioxidative effects of irisin. Our findings unveil a novel therapeutic mechanism for AP, wherein irisin inhibits KEAP1 to alleviate OS. Increasing irisin levels in vivo presents a promising strategy for AP treatment.

Previous studies have suggested an association between inflammatory bowel disease (IBD), and pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). We aimed to examine the potential causal relationship between IBD and pancreatitis using the Mendelian randomization (MR) method.

We obtained data from genome-wide association studies (GWASs) in European individuals for IBD and its main subtypes, Crohn's disease (CD) and ulcerative colitis (UC) (31,665 IBD cases, 13,768 UC cases, 17,897 CD cases and 33,977 controls). Four independent summary statistics of pancreatitis from the the European Bioinformatics Institute (EMBL-EBI, 10,630 AP cases and 844,679 controls, 1,424 CP cases and 476,104 controls) and FinnGen Consortium (8,446 AP cases, 4,820 CP cases and 437,418 controls) were used for bidirectional MR analyses and sensitivity analysis. Finally, further meta-analysis was conducted on the MR results.

Generally, IBD is associated with an increased risk of pancreatitis (IBD-AP, OR = 1.050, 95% CI 1.020-1.080, P = 7.20 × 10-5; IBD-CP, OR = 1.050, 95% CI 1.010-1.090, P = 0.019). In addition, UC increased the risk of pancreatitis (UC-AP, OR = 1.050, 95% CI 1.020-1.070, P = 9.10 × 10-5; UC-CP, OR = 1.090, 95% CI 1.040-1.140, P = 1.44 × 10-4) and CD increased the risk of acute pancreatitis (OR = 1.040, 95% CI 1.020-1.060, P = 9.61 × 10-5). However, no causal association was found between CD and the risk of chronic pancreatitis (P > 0.05). The reverse MR results showed that AP may be associated with a reduced risk of IBD and CD (AP-IBD, OR = 0.880, 95% CI 0.810-0.960, P = 0.003; AP-CD, OR = 0.830, 95% CI 0.730-0.940, P = 0.003). However, there is no causal relationship between AP and the risk of UC, and there is no causal relationship between CP and the risk of IBD and its subtypes(P > 0.05).

In conclusion, based on MR analysis and meta-analysis, our results showed a positive causal effect of IBD on pancreatitis, and subgroup analyses showed that UC and CD may promote the development of acute pancreatitis, whereas UC may promote the development of chronic pancreatitis. Reverse MR analysis suggests that AP may have a potential protective effect on IBD and CD.

This study aims to evaluate the clinical efficacy of pancreatic duct stenting in the treatment of SAP, providing reference for clinical diagnosis and treatment.

A retrospective analysis was conducted on clinical data from patients with SAP admitted to the General Hospital of Ningxia Medical University from June 1, 2019 to December 31, 2022. A total of 51 patients were included (33 males, 18 females). Patients were divided into two groups based on treatment: the control group (n = 28) receiving conventional treatment and the stent group (n = 23) undergoing pancreatic duct stenting in addition to conventional treatment. Data collected and analyzed include demographic information, rates of late local complications, late surgical interventions, new-onset OF, infected pancreatic necrosis and new-onset systemic complications. Specific outcomes measured were incidences of new-onset respiratory, renal and circulatory failure, single and multiple OF, sepsis, ACS, abdominal hypertension, and pancreatogenic encephalopathy, as well as use of ≥ 3 types of antibiotics, time of antibiotic use, time of analgesic administration, oral refeeding, length of hospital stay, ICU care, and length of ICU stay. These indicators were used to assess the therapeutic efficacy of pancreatic duct stenting.

All 23 patients in the stent group successfully underwent stenting. The incidence of new-onset OF and new-onset systemic complications was significantly lower in the stent group compared to the control group (χ2 = 4.96, 6.65, P < 0.05). However, no significant differences were observed between the groups regarding late local complications, infected pancreatic necrosis, and late surgical intervention (χ2 = 0.22, 0.002, 0.024, P > 0.05). Notably, two patients in the control group required additional procedures due to inadequate drainage, with one undergoing endoscopic debridement and the other, laparotomy. Mortality rates were 3 (10.7%) in the control group and 4 (17.4%) in the stent group, with no statistically significant difference (P > 0.05). Furthermore, significant differences were noted in new-onset respiratory failure, single OF, sepsis, abdominal hypertension, time of analgesic administration, oral refeeding, length of enzyme inhibitor use, and hospitalization expenses (χ2 = 3.94, 4.37, 5.79, 4.79; Z = - 2.008, - 4.176, - 4.165, - 2.309; P < 0.05). No significant differences were found in new-onset renal, circulatory, multiple OF, ACS, pancreatogenic encephalopathy, use of ≥ 3 types of antibiotics, time of antibiotic use, length of hospital stay, ICU care, and length of ICU stay (P > 0.05).

Pancreatic duct stenting effectively reduces the incidence of new-onset systemic complications and OF in SAP, preventing further deterioration. Pancreatic duct stenting can alleviate symptoms, shorten oral refeeding, and promote patient recovery.

This study was recorded as a single-center, retrospective case-control study (ChiCTR1900025833).

Transfer RNA (tRNA)-derived fragments, a new type of tRNA-derived small RNA (tsRNA), can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels. tsRNAs are not only degradation fragments but also have biological functions, including those in immune inflammation, metabolic disorders, and cell death. tsRNA dysregulation is closely associated with multiple diseases, including various cancers and acute pancreatitis (AP). AP is a common gastrointestinal disease, and its incidence increases annually. AP development is associated with tsRNAs, which regulate cell injury and induce inflammation, especially pyroptosis and ferroptosis. Notably, serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP. We show the characteristics of tsRNAs and their diagnostic value and function in AP, and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.

Background: Acute pancreatitis is a common condition with a variable prognosis. While the overall mortality rate of acute pancreatitis is relatively low, ranging between 3 and 5% in most cases, severe forms can result in significantly higher morbidity and mortality. Therefore, early risk assessment is crucial for optimizing management and treatment. The aim of the present study wasto compare simple prognostic markers and identify the best predictors of severity in patients with acute pancreatitis. Material and Methods: A retrospective analysis was carried outon 108 patients admitted in our center during one year with acute biliary pancreatitis. Acute pancreatitis severity was stratified based on the revised Atlanta criteria. Results: 108 subjects (mean age of 60.1 ± 18.6, 65.7% females) diagnosed with acute biliary pancreatitis were included. Based on the Atlanta criteria, 59.3% (64/108) of the subjects were classified as having mild acute biliary pancreatitis, 35.2% (38/108) as having a moderate-severe pancreatitis, and 5.5% (6/108) were classified as having severe acute pancreatitis. In univariate analysis, the following parameterswere associatedwith at least a moderate-severe form of acute pancreatitis: Balthazar score, fasting blood glucose (mg/dL), modified CTSI score, CRP values at 48 h, BISAP score at admission, CTSI score, Ranson score, duration of hospitalization (days), and the presence of leukocytosis (×1000/µL) (all p < 0.05).BISAP score at admission (AUC-0.91), CRP levels at 48 h (AUC-0.92), mCTSI (AUC-0.94), and CTSI score (AUC-0.93) had the highest area under the curve (AUC) for predicting the severity of acute pancreatitis. In multivariate analysis, the model including the following independent parameters was predictive for the severity of acute pancreatitis: CTSI score (p < 0.0001), BISAP score (p = 0.0082), and CRP levels at 48 h (p = 0.0091), respectively. The model showed a slightly higher AUC compared to the independent predictors (AUC-0.96). Conclusions: The use of a multiparametric prediction model can increase the accuracy of predicting severity in patients with acute biliary pancreatitis.

The study was to explore the efficacy and safety of sivelestat (SV) in the treatment of severe acute pancreatitis (SAP) with systemic inflammatory response syndrome (SIRS). A total of 102 SAP patients diagnosed and treated in the Emergency Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from January 2021 to August 2024 were selected. The changes of disease outcome, hospital stays and mortality were compared between the two groups. A total of 102 patients were recruited to control group (n = 56) or SV group (n = 46) according to whether SV was applied or not. There was no significant difference in baseline data at admission between the two groups. After 1 week of treatment, all the indexes in both groups improved. The duration of ventilator use (p = 0.0400) and ICU stays (p  = 0.0495) in SV group was shorter than that in control group, but there was no significant difference in mortality between the two groups. Although SV did not reduce the mortality of patients with SAP, it reduced the length of ventilator use and ICU stay.

Pancreatitis is a severe inflammatory condition characterized by damage to the pancreas. Sterol o-acyltransferase 2 (SOAT2) has been reported to aggravate acute pancreatitis, however, the underlying mechanism remains to be elucidated. Rat pancreatic exocrine cells (AR42J) were treated with caerulein to induce pancreatitis-like cellular injury. Cell viability was determined using a cell counting kit-8 (CCK-8) assay, while cell proliferation was analyzed through a 5-Ethynyl-2'-deoxyuridine assay. Cell apoptosis was measured using flow cytometry, and enzyme-linked immunosorbent assays were performed to detect levels of pro-inflammatory cytokines IL-6 and TNF-α. Additionally, Fe2+ levels were analyzed using a colorimetric assay kit, reactive oxygen species (ROS) levels were assessed with a Cellular ROS Assay kit, and lipid peroxidation was measured using a malondialdehyde assay kit. Glutathione levels were analyzed with a detection assay. Protein and mRNA expression were evaluated through western blotting and quantitative real-time polymerase chain reaction, respectively. Furthermore, an RNA immunoprecipitation assay was conducted to investigate the association between ELAV-like RNA binding protein 1 (ELAVL1) and SOAT2. Actinomycin D assay was performed to explore the effect of ELAVL1 depletion on the transcript stability of SOAT2 mRNA. SOAT2 and ELAVL1 expression were upregulated in caerulein-exposed AR42J cells. Caerulein treatment induced pancreatitis-like cellular apoptosis, inflammatory response, ferroptosis, and cell proliferation inhibition. Silencing of SOAT2 protected against caerulein-induced AR42J cell injury. Moreover, ELAVL1 stabilized SOAT2 mRNA expression in AR42J cells. SOAT2 overexpression attenuated the effects induced by ELAVL1 silencing in caerulein-exposed AR42J cells. Additionally, ELAVL1 knockdown activated the NRF2/HO-1 pathway by downregulating SOAT2 expression in caerulein-exposed AR42J cells. SOAT2 silencing protected AR42J cells from caerulein-induced injury by inactivating the NRF2 pathway. In conclusion, ELAVL1-dependent SOAT2 exacerbated pancreatic exocrine cell injury by inactivating the NRF2/HO-1 pathway in pancreatitis. These findings provide new insights into the molecular mechanisms underlying pancreatitis and offer potential therapeutic targets for the treatment of this condition.

This study aimed to thoroughly examining the causal link between immune traits and four types of pancreatitis, using mendelian randomization.

Data on 731 immune traits were collected from the genome-wide association study (GWAS) database as exposure. Information regarding acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) were acquired from the FinnGen Consortium as outcomes. Mendelian randomization (MR) using inverse variance weighting (IVW) evaluated the links between immune traits and pancreatitis. We evaluated the robustness of the IVW results through sensitivity analyses and validated them using meta-analysis with AP and CP data from the UK Biobank in the GWAS catalog.

A total of 36 immune traits showed significant associations with susceptibility of four types of pancreatitis, including AP (7 traits), AAP (8 traits), CP (14 traits), and ACP (7 traits). Twenty characteristics were found to be potential risk factors for pancreatitis, identified in B Cells (5 traits), conventional dendritic cells (cDCs, 2 traits), maturation stage of T cells (2 traits), monocytes (2 traits), myeloid cells (2 traits), T cells, B cells, natural killer cells (TBNK, 2 traits), and regulatory T cells (Treg cells, 5 traits). Multiple sensitivity analyses confirmed the validity of the findings. Meta-analysis confirmed a solid causal relationship between CX3CR1 on CD14- CD16-of monocyte panel and the susceptibility of CP.

Our MR study identified immune traits causally linked to acute and chronic pancreatitis, offering new insights for early clinical intervention and immune cell-targeted therapies.

Acute kidney injury (AKI) is a common and serious complication in severe acute pancreatitis (AP), associated with high mortality rate. Early detection of AKI is crucial for prompt intervention and better outcomes. This study aims to develop and validate predictive models using machine learning (ML) to identify the onset of AKI in patients with AP.

Patients with AP were extracted from the MIMIC-IV database. We performed feature selection using the random forest method. Model construction involved an ensemble of ML, including random forest (RF), support vector machine (SVM), k-nearest neighbors (KNN), naive Bayes (NB), neural network (NNET), generalized linear model (GLM), and gradient boosting machine (GBM). The best-performing model was fine-tuned and evaluated through split-set validation.

We analyzed 1,235 critically ill patients with AP, of which 667 cases (54%) experienced AKI during hospitalization. We used 49 variables to construct models, including GBM, GLM, KNN, NB, NNET, RF, and SVM. The AUC for these models was 0.814 (95% CI, 0.763 to 0.865), 0.812 (95% CI, 0.769 to 0.854), 0.671 (95% CI, 0.622 to 0.719), 0.812 (95% CI, 0.780 to 0.864), 0.688 (95% CI, 0.624 to 0.752), 0.809 (95% CI, 0.766 to 0.851), and 0.810 (95% CI, 0.763 to 0.856) respectively. In the test set, the GBM's performance was consistent, with an area of 0.867 (95% CI, 0.831 to 0.903).

The GBM model's precision is crucial, aiding clinicians in identifying high-risk patients and enabling timely interventions to reduce mortality rates in critical care.

The purpose of the research is to design an algorithm to predict the occurrence of acute respiratory failure (ARF) in patients with acute pancreatitis (AP).

We collected data on patients with AP in the Medical Information Mart for Intensive Care IV database. The enrolled observations were randomly divided into a 70 % training cohort and a 30 % validation cohort, and the observations in the training cohort were divided into ARF and non-ARF groups. Feature engineering was conducted using random forest (RF) and least absolute shrinkage and selection operator (LASSO) methods in the training cohort. The model building included logistic regression (LR), decision tree (DT), k-nearest neighbours (KNN), naive bayes (NB) and extreme gradient boosting (XGBoost). Parameters for model evaluation include receiver operating characteristic (ROC) curve, precision-recall curve (PRC), calibration curves, positive predictive value (PPV), negative predictive value (NPV), true positive rate (TPR), true negative rate (TNR), accuracy (ACC) and F1 score.

Among 4527 patients, 445 patients (9.8 %) experienced ARF. Ca, ALB, GLR, WBC, AG and BUN have been included in the prediction model as features for predicting ARF. The AUC of XGBoost were 0.86 (95 %CI 0.84-0.88) and 0.87 (95 %CI 0.84-0.90) in the training and validation cohorts. In the training cohort, XGBoost demonstrates a true positive rate (TPR) of 0.662, a true negative rate (TNR) of 0.884, a positive predictive value (PPV) of 0.380, a negative predictive value (NPV) of 0.960, an accuracy (ACC) of 0.862, and an F1 score of 0.483. In the validation cohort, XGBoost shows a TPR of 0.620, a TNR of 0.895, a PPV of 0.399, an NPV of 0.955, an ACC of 0.867, and an F1 score of 0.486.

The XGBOOST model demonstrates good discriminatory ability, which enables clinicians to ascertain the probability of developing ARF in AP patients.

Glucagon-like peptide-1 (GLP-1) receptor agonists, including tirzepatide (Mounjaro), are widely used to manage type 2 diabetes mellitus (T2DM) and obesity. While gastrointestinal side effects are common, acute pancreatitis remains a rare but significant complication. Limited evidence exists on the risks associated with switching between GLP-1 agonists, emphasizing the need for clinical awareness. We present a 59-year-old male with T2DM, hyperlipidemia, and hypertension, who was recently transitioned from semaglutide (Ozempic) to tirzepatide (Mounjaro). He presented with acute epigastric pain, nausea, and vomiting two days after initiating tirzepatide. Laboratory findings revealed elevated lipase levels (847 U/L), leukocytosis, and diagnostic imaging confirming acute pancreatitis with other causes ruled out. Supportive care improved symptoms initially, but the clinical course was complicated by fevers prompting repeat imaging, revealing worsening pancreatitis with colonic involvement and pleural effusion. The patient was treated with empiric antibiotics and supportive measures, resulting in resolution of symptoms. Tirzepatide was discontinued, with a follow-up arranged for glycemic management. Acute pancreatitis is a rare but documented adverse effect of GLP-1 agonists, with limited cases reported in the literature. Switching between GLP-1 agonists may increase the risk of adverse effects, especially if appropriate dose titration protocols are not followed. This case highlights the recognition of acute pancreatitis as a potential adverse effect of GLP-1 agonists when initiating or transitioning GLP-1 therapies and following titration protocols to help avoid this complication. GLP-1 agonists, including tirzepatide, offer significant therapeutic benefits for T2DM and obesity but carry risks of rare adverse effects like acute pancreatitis. Greater awareness, careful dose adjustments, and vigilant monitoring are essential to optimizing patient safety. Further research is needed to elucidate the safety profile of switching between GLP-1 agonists to guide clinical practice and improve patient outcomes.

Hepatoid adenocarcinoma of the pancreas is a rare aggressive tumor with poor prognosis. We describe contrast-enhanced CT and FDG PET/CT findings in a case of pancreatic hepatoid adenocarcinoma with significantly elevated α-fetoprotein level presenting as acute pancreatitis. The primary pancreatic tumor diffusely involved the pancreas and showed heterogeneous enhancement mimicking acute necrotizing pancreatitis on contrast-enhanced CT. FDG PET/CT showed intense FDG uptake (SUV max , 24.5) of the left supraclavicular and retroperitoneal lymph node metastases, suggesting FDG PET/CT may be useful for staging of this aggressive tumor.

This study aims to develop and validate an integrated predictive model combining CT radiomics and clinical parameters for early assessment of acute pancreatitis severity.

A retrospective cohort of 246 patients with acute pancreatitis was analyzed, with a 70%-30% split for training and validation groups. CT image segmentation was performed using ITK-SNAP, followed by the extraction of radiomics features. The stability of the radiomics features was assessed through inter-observer Intraclass Correlation Coefficient analysis. Feature selection was carried out using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. A radiomics model was constructed through logistic regression to compute the radiomics score. Concurrently, univariate and multivariate logistic regression were employed to identify independent clinical risk factors for the clinical model. The radiomics score and clinical variables were integrated into a combined model, which was visualized with a nomogram. Model performance and net clinical benefit were evaluated through the area under the receiver operating characteristic curve (AUC), the DeLong test, and decision curve analysis.

A total of 913 radiomics features demonstrated satisfactory consistency. Eight features were selected for the radiomics model. Serum calcium, C-reactive protein, and white blood cell count were identified as independent clinical predictors. The AUC of the radiomics model was 0.871 (95% CI, 0.793-0.949) in the training cohort and 0.859 (95% CI, 0.751-0.967) in the validation cohort. The clinical model achieved AUCs of 0.833 (95% CI, 0.756-0.910) and 0.810 (95% CI, 0.692-0.929) for the training and validation cohorts, respectively. The combined model outperformed both the radiomics and clinical models, with an AUC of 0.905 (95% CI, 0.837-0.973) in the training cohort and 0.908 (95% CI, 0.824-0.992) in the validation cohort. The DeLong test confirmed superior predictive performance of the combined model over both the radiomics and clinical models in the training cohort, and over the clinical model in the validation cohort. Decision curve analysis further demonstrated that the combined model provided greater net clinical benefit than the radiomics or clinical models alone.

The clinical-radiomics model offers a novel tool for the early prediction of acute pancreatitis severity, providing valuable support for clinical decision-making.