Acute pancreatitis (AP) is a common acute abdominal condition in clinical practice, associated with high morbidity and mortality rates. Forsythia constitutes a component of traditional Chinese medicinal decoctions used for clinical AP treatment; however, the efficacy of its active monomer in treating AP has yet to be completely substantiated. Here, we engineered an AP cell and mouse model by administering a combination of caerulein and LPS. In vitro experiments utilizing AR42J cells demonstrated that forsythoside B (FST·B) was the most effective monomer in mitigating cellular inflammation. Subsequently, a comprehensive evaluation of FST·B concentrations and efficacy was performed in animal models. Next Mass spectrometry analysis of pancreatic from AP mice treated with 50 mg/kg FST·B was conducted to elucidate its primary regulatory molecular signaling and key targets. FST·B effectively mitigated pathological damage in mice with acute pancreatitis, leading to a reduction in the expression of inflammatory cytokines in both pancreatic tissue and serum. Proteomics and phosphoproteomic profiles revealed that FST·B significantly enhanced the level of oxidative phosphorylation and spliceosome pathway in the AP mice. This research provides initial evidence of the regulatory molecular signals and targets of FST·B in AP, laying a potential foundation for its clinical use in treating AP. SIGNIFICANCE: Acute pancreatitis (AP) is a common acute abdominal condition in clinical practice, associated with high morbidity and mortality rates, and the global incidence of AP has increased by approximately 25 % over the past 15 years. Despite the complexity of AP's causes and the high susceptibility of proteins to degradation during lesions, systems biology studies, such as proteomics, have been limited in investigating the molecular mechanisms involved in its pharmacological treatment. Forsythoside B, a phenylethanol glycoside isolated from the air-dried fruit of forsythia, is a traditional oriental anti-inflammatory drug commonly used in clinical practice. We demonstrated in the AP mouse model that forsythoside B can alleviate pancreatic inflammatory damage in vivo. To elucidate the molecular mechanisms underlying the anti-inflammatory effect of forsythoside B, a comprehensive proteomic and phosphoproteomic analysis was conducted on AP mice models prior to and subsequent to forsythoside B intervention. Finally, 1640 significantly differentially expressed proteins, 1448 significantly differentially expressed phosphoproteins corresponding to 2496 significantly differentially expressed phosphosites were identified. Functional analysis revealed that forsythoside B significantly enhanced the level of oxidative phosphorylation in the AP mice in proteomic profiles, and the spliceosome pathway at the phosphorylation level was significantly affected by forsythoside B. This research provides initial evidence of the regulatory molecular signals and targets of forsythoside B in AP, laying a potential foundation for its clinical use in treating AP.

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 cause of emergency hospital admissions, putting a substantial burden on the healthcare system. The clinical course of AP is usually mild and often resolves without a sequel. Severe AP (SAP) is associated with an intense inflammatory response leading to localized or systemic complications and significant morbidity and mortality (American Gastroenterological Association). Early diagnosis and precise assessment of disease severity are imperative during initial evaluation in patients with AP, as it has a bearing on deciding the course of management and prognosticating the disease outcome.

Eighty-six cases of AP treated in our institution between July 2022 and August 2024 were prospectively enrolled in the study. The patients underwent detailed clinical evaluation, and the Acute Physiology and Chronic Health Evaluation II (APACHE II), Bedside Index of Severity in Acute Pancreatitis (BISAP), and Ranson scores were calculated. Ranson was again calculated after 48 hours of admission. Contrast-enhanced computed tomography of the abdomen was done in all patients after 72 hours of the onset of pain, and a modified computed tomography severity index (mCTSI) was calculated. Data regarding patients was collected and correlated with the outcome.

During the course of the disease, seven (8.1%) patients died, while 79 (91.9%) improved. The majority of the patients, five of the seven patients (71.4%) who died, had SAP. On ROC curve analysis, Ranson was found to be the best predictor of SAP (area under the curve (AUC): 0.97), followed by APACHE II (AUC: 0.95), mCTSI (AUC: 0.95), and BISAP (AUC: 0.87). mCTSI was found to be the best predictor of pancreatic necrosis (AUC: 0.94), followed by Ranson (AUC: 0.87), APACHE-II (AUC: 0.78), and BISAP (AUC: 0.52). APACHE II had a slight edge over the rest of the scoring system in mortality predicting (APACHE II AUC: 0.72 95% CI (0.58-0.85), BISAP AUC: 0.67 95% CI (0.52-0.80), Ranson AUC: 0.68 95% CI (0.54-0.80), and mCTSI AUC: 0.72 95% CI (0.58-0.85)).

The ROC curve analysis demonstrated that Ranson was superior to the other scoring systems for predicting severity, and APACHE II had the highest accuracy for mortality.

Severe acute pancreatitis (SAP) is a severe clinical condition associated with high rates of morbidity and mortality. Multiple organ dysfunction syndrome that follows systemic inflammatory response syndrome is the leading cause of SAP‑related death. Since the inflammatory mechanism of SAP remains unclear, there is currently a lack of effective drugs available for its treatment. Therefore, it is important to study effective therapeutic drugs and their molecular mechanisms based on studying the inflammatory mechanism of SAP. In the present study, in vivo, a mouse model of AP induced by cerulein (CR) combined with lipopolysaccharide (LPS) was established to clarify the therapeutic effect of artesunate (AS) in AP mice by observing the gross morphological changes of the pancreas and surrounding tissues, calculating the pancreatic coefficient, and observing the histopathology of the pancreas. The serum amylase activity in AP mice was detected by iodine colorimetry and the superoxide dismutase activity in the pancreas was detected by WST‑1 assay. The levels of proinflammatory cytokines in the serum, the supernatant of pancreatic tissue homogenates and the peritoneal lavage fluid were detected by ELISA assay. The total number of peritoneal macrophages was assessed using the cellular automatic counter, and the expression of proteins related to autophagy, and the TLR4 pathway was detected by immunohistochemistry and western blotting. In vitro, the effect of trypsin (TP) combined with LPS was observed by detecting the release of proinflammatory cytokine levels from macrophages by ELISA assay, and detecting the expression of proteins related to autophagy and the TLR4 pathway by immunofluorescence and western blotting. The present study revealed that AS reduced pancreatic histopathological damage, decreased pancreatic TP and serum amylase activities, increased superoxide dismutase activity, and inhibited pro‑inflammatory cytokine levels in a mouse model of AP induced by cerulein combined with lipopolysaccharide. In vitro, TP combined with LPS was found to synergistically induce pro‑inflammatory cytokine release from mouse macrophages and RAW264.7 cells, while AS could inhibit cytokine release. Furthermore, CR combined with LPS synergistically increased amylase activity in acinar cells, whereas AS decreased amylase activity. Autophagy serves an important role in the release of pro‑inflammatory cytokines. In the present study, it was revealed that the autophagy inhibitor LY294002 suppressed the release of pro‑inflammatory cytokines from macrophages treated with TP combined with LPS, and pro‑inflammatory cytokine release was not further reduced by AS combined with LY294002. Furthermore, AS not only inhibited the expression of important molecules in the Toll‑like receptor 4 (TLR4) signaling pathway, but also inhibited autophagy proteins and reduced the number of autolysosomes in mice with AP and in macrophages. In conclusion, these results suggested that AS may protect against AP in mice via inhibition of TLR4‑dependent autophagy; therefore, AS may be considered a potential therapeutic agent against SAP.

Background and Objectives: Acute pancreatitis (AP) is an inflammatory disease where there is autodigestion of the pancreas by prematurely activated enzymes which may lead to a systemic inflammatory response. The aim of our study was to investigate the levels of circulating serum leukotriene B4 (LTB4), lipoxin A4 (LXA4), and resolvin D1 (RvD1) in pancreatitis due to gallstones in the etiologic investigation of AP. Materials and Methods: A total of 147 patients with AP (n: 49), AC (n: 49), and combined AP + AC (n: 49) will be included in the study. Healthy volunteers (n: 49) will be included as the control group. Results: RvD1 levels were significantly lower in patient groups compared to controls, while LXA4 levels were lower in patients with combined AP + AC (145.24 ng/L) compared to both controls (312.36 ng/L) and other patient groups. LTB4 levels were elevated in all patient groups compared to controls (335.56 ng/L vs. 65.56 ng/L) and were highest in combined AP + AC. Significant correlations were identified: RvD1 showed a negative correlation with LTB4 (r =-0.676; p < 0.001) and a positive correlation with LXA4 (r = 0.563, p < 0.001). ROC analysis demonstrated high diagnostic accuracy, with LXA4 and LTB4 achieving perfect differentiation (AUC: 1.0) between control and combined AP + AC cases. Conclusions: Our study showed that serum RvD1 and LXA4 levels have powerful anti-inflammatory properties in accordance with the literature. LTB4 may represent new, effective indicators to predict the severity of AP and the presence of necrosis in patients with AP. Despite its low sensitivity and specificity, RvD1 could be used as a complementary marker to the current scoring systems for the initial assessment of AP prognosis. These findings provide a new mechanistic understanding of how RvD1 attenuates inflammation to facilitate resolution, which could help develop novel therapeutic strategies for diseases caused by unresolved inflammation. It is easily obtainable and can provide additional prognostic information to clinicians.

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).

Bleeding is a rare but serious complication of pancreatitis, significantly increasing morbidity and mortality. It can arise from various sources, including erosion of blood vessels by inflammatory processes, formation of pseudoaneurysms, and gastrointestinal bleeding. Early diagnosis and timely intervention are crucial for patient survival. Imaging modalities such as computed tomography and angiography are essential for identifying the bleeding source, where endoscopy may help in detecting and treating intraluminal hemorrhage. Management strategies for patients with extraluminal bleeding may involve angioembolization or surgical intervention, depending on the severity and location of the bleeding. While advances in diagnostic and therapeutic techniques have improved outcomes, bleeding in pancreatitis remains a challenging clinical problem requiring a multidisciplinary approach. This review aims to focus its attention specifically on the bleeding complications of pancreatitis.

Acute pancreatitis (AP) represents a severe inflammatory condition of the exocrine pancreas, precipitating systemic organ dysfunction and potential failure. The global prevalence of acute pancreatitis is on an ascending trajectory. The condition carries a significant mortality rate during acute episodes. This underscores the imperative to elucidate the etiopathogenic pathways of acute pancreatitis, enhance comprehension of the disease's intricacies, and identify precise molecular targets coupled with efficacious therapeutic interventions. The pathobiology of acute pancreatitis encompasses not only the ectopic activation of trypsinogen but also extends to disturbances in calcium homeostasis, mitochondrial impairment, autophagic disruption, and endoplasmic reticulum stress responses. Notably, the realm of epigenetic regulation has garnered extensive attention and rigorous investigation in acute pancreatitis research over recent years. One of these modifications, lysine acetylation, is a reversible post-translational modification of proteins that affects enzyme activity, DNA binding, and protein stability by changing the charge on lysine residues and altering protein structure. Numerous studies have revealed the importance of acetylation modification in acute pancreatitis, and that it is a favorable target for the design of new drugs for this disease. This review centers on lysine acetylation, examining the strides made in acute pancreatitis research with a focus on the contributory role of acetylomic alterations in the pathophysiological landscape of acute pancreatitis, thereby aiming to delineate novel therapeutic targets and advance the development of more efficacious treatment modalities.

The purpose of this review is to examine the current scientific literature regarding the interplay between the exocrine and endocrine pancreas, specifically the role of the exocrine pancreas in the pathogenesis of canine diabetes mellitus. β-cell death caused by exocrine pancreatic inflammation is thought to be an under-recognised contributor to diabetes mellitus in dogs, with up to 30 % of canine diabetic patients with concurrent evidence of pancreatitis at post-mortem examination. Current diagnostics for pancreatitis are imprecise, and treatments for both diseases individually have their own limitations: diabetes through daily insulin injections, which has both welfare and financial implications for the stakeholders, and pancreatitis through treatment of clinical signs, such as analgesia and anti-emetics, rather than targeted treatment of the underlying cause. This review will consider the evidence for exocrine pancreatic inflammation making an active contribution to pancreatic β-cell loss and insulin-deficiency diabetes in the dog and explore current and potential future diagnostic and treatment avenues to improve outcomes for these patients.

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.

A conservative strategy is the primary modality of treatment for acute pancreatitis of which fluid replacement is an important component. Since the results regarding early aggressive versus moderate fluid replenishment for acute pancreatitis are inconsistent, we sought to compare outcomes between the two resuscitation strategies in our meta-analysis.

We searched MEDLINE (PubMed), Embase, the Cochrane Library, and ClinicalTrials.gov for all available randomized controlled trials (RCTs) assessing outcomes for patients treated with aggressive fluid replacement compared to moderate fluid replacement. Our primary outcome was all-cause mortality.

Our meta-analysis included 6 RCTs involving a total of 632 patients. Our results showed that aggressive fluid resuscitation increased the risk of all-cause mortality as compared to moderate fluid replacement (RR 2.40, CI: 1.38-4.19). For all of our secondary outcomes which included the development of organ failure, severe pancreatitis, pancreatic necrosis, clinical improvement, development of SIRS, persistent SIRS, and length of hospital stay, the results indicate that there was no significant difference between the two groups.

Aggressive fluid resuscitation is associated with higher mortality as compared to moderate fluid replacement in patients with acute pancreatitis. RCTs with larger sample sizes are needed to provide greater statistical power and establish more definitive conclusions.

The acute and chronic pancreatitis (CP) can lead to severe complications like walled-off necrosis, large symptomatic pseudocyst or multiorgan failure. The treatment of these complications is multivariate and can differ from conservative, symptomatic treatment or minimal-invasive, endoscopic transgastral stenting to transgastral necrosectomy.

This study aims to analyse the clinical course for patients that develop local complications of severe pancreatitis.

This is a retrospective observational single-centre study on 46 patients with severe pancreatitis.

In this retrospective single-centre study, 46 out of 474 inpatients from January 2014 to December 2020, who were treated because of an acute or CP, developed acute pancreatitis complications and could be included. We analysed and compared the clinical course of different treatments (lumen apposing metal stents, transgastral double pigtail stent, endoscopic retrograde cholangiopancreatography, operation, conservative treatment) and different complications (walled-off necrosis (WON), pancreatic pseudocyst (PPC)).

Forty-six patients developed an acute complication due to severe pancreatitis. Twenty-seven patients developed a WON, while 19 patients suffered from PPC. 48% of the whole cohort had an alcoholic aetiology of pancreatitis. 78% were treated with antibiotics, 48% suffered from infected pancreatitis and 22% needed intensive care treatment. WON patients more often had a longer hospitalization of more than 21 days. PPC patients were correlated with an alcoholic aetiology, whereas WON patients were inversely correlated with an alcoholic aetiology. Increased lactate dehydrogenase, lipase, and C-reactive protein levels as well as leucocyte count could be associated with a higher probability to exhibit a WON instead of another local complication. The mortality rate was low with 7% in our study.

WON and PPC differ in certain patients and laboratory characteristics such as aetiology, elevated laboratory values, antibiotic treatment or the duration of hospitalization. Invasive treatment is not required in all severe pancreatitis cases.

The serum albumin-to-serum creatinine ratio (sACR) is independently associated with the prognosis of multiple diseases. However, its relationship with in-hospital mortality of patients with severe acute pancreatitis (SAP) remains unclear.

Patients diagnosed with SAP between April 2016 and December 2023 were collected. These patients were categorized into low and high sACR groups based on an optimal cut-off value calculated using Youden's index. Multivariate logistic regression analysis was utilized to examine the relationship between sACR levels and the in-hospital mortality. Additionally, a limited restricted cubic spline (RCS) method was employed to evaluate the nonlinear relationship between sACR values and the risk of in-hospital mortality. The potential for unmeasured confounders between sACR levels and in-hospital mortality was also explored through the calculation of the E value.

A total of 114 eligible patients were included in this sutdy. The multivariate logistic regression analysis indicated an independent association between sACR levels and in-hospital mortality (p < 0.001). The RCS analysis demonstrated a linear correlation between sACR values and the risk of in-hospital mortality (P for non-linearity > 0.05), where the risk increased as the sACR value decreased.

The research findings suggest that sACR levels are independently associated with in-hospital mortality of patients with SAP, providing a means for early identification of those at high risk of in-hospital mortality. This early identification may facilitate the optimizing and strengthening of treatments, ultimately leading to improved outcomes.

Protectin D1 (PD1), a biologically active molecule derived from docosahexaenoic acid (DHA), plays a major role in the body's endogenous lipid-mediated inflammatory response. The study aims to explore the relationship between PD1, inflammatory response and the severity of acute pancreatitis (AP).

Sixty consecutive AP patients within 72h of disease onset were enrolled as the study group, a further thirty healthy people were enrolled as the control group. General demographics collected at the time of enrollment. Serum PD1, Citrullinated Histone 3 (CitH3), myeloperoxidase-Deoxyribonucleic acid (MPO-DNA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level were measured in AP patients on enrollment day 0, day 1, day 3 and day 7. Meanwhile, the Acute Physiology and Chronic Health evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores were also evaluated on day 0, day 1, day 3 and day 7.

AP was severe in 29 patients (48.3%), moderately severe acute pancreatitis (MSAP) was found in 9 patients (15%), and mild acute pancreatitis (MAP) was found in 22 patients (36.7%). The level of PD1, CitH3 and MPO-DNA were statistically significantly higher in AP patients than in the healthy population. Serum PD1, CitH3 and MPO-DNA concentration increased with AP severity. In AP patients, PD1 has a strong linear association with TNF-α, CitH3 and MPO-DNA. The AUC for SAP predicted by PD1 was 0.938. The calculated cut-off point for prognosis SAP is 7.94 pg/mL. The AUC for infected pancreatic necrosis (IPN) predicted by PD1 was 0.836 and the cut-off point was 8.65 pg/mL. The AUC for organ failure (OF) predicted by PD1 was 0.719 and the cut-off point was 7.94 pg/mL.

PD1 is associated with both the presence of AP and the severity of pancreatitis.

The purpose of this review is to provide a practical guide for the clinical care of patients with acute pancreatitis (AP) from the management of the early phases of disease to the treatment of local complications. AP is one of the most frequent causes of gastroenterological admission in emergency departments. It is characterized by a dynamic and unpredictable course and in its most severe forms, is associated with organ dysfunction and/or local complications, requiring intensive care with significant morbidity and mortality. Initial therapy includes adequate fluid resuscitation, nutrition, analgesia, and when necessary critical care support. In recent years, the development of minimally invasive tailored treatments for local complications, such as endoscopic drainage, has improved patients' acceptance and outcomes. Despite this, the management of AP remains a challenge for clinicians. The present review was conducted by the authors, who formulated specific questions addressing the most critical and current aspects of the clinical course of AP with the aim of providing key messages.

In this study, we developed a sensitive method for monitoring α-amylase using a fluorogenic approach based on the host-guest complexation between an amphiphilic pyrenyl derivative (1) and γ-cyclodextrins (γ-CDs). The compound 1 self-assembles into nanofibrils in aqueous solutions. Upon the introduction of γ-CD, compound 1 forms an inclusion complex with it. This complex then participates in the formation of a 2 : 2 complex with another complex, leading to strong excimer fluorescence. Upon interaction with α-amylase, γ-CD undergoes hydrolysis, leading to the regeneration of nanofibrils, which is accompanied by a decrease in excimer fluorescence and an increase in monomeric fluorescence. This ratiometric fluorescence color change enables the sensitive detection of low levels of α-amylase in human urine, offering a practical approach for early screening of pancreatic-related diseases.

Shenfu Injection (SFI) has emerged as a prevalent therapeutic intervention in clinical practice for the management of acute pancreatitis (AP). The purpose of this research was to investigate and validate the potential mechanisms of SFI in the treatment of AP through network pharmacology.

Network pharmacology was adopted to investigate the potential targets and mechanisms of SFI in the treatment of AP. Molecular docking was employed to evaluate the binding affinity between active components and targets. Single-cell transcriptome analysis was conducted to explore the cell types associated with SFI treatment in AP. In vitro and in vivo models of AP were induced by caerulein. The histopathological changes were observed by HE staining. Cell apoptosis was detected using flow cytometry and Tunel staining. Cell viability was assessed using CCK-8 assay. Western blot and ELISA were used to detect the protein expression and inflammatory cytokines, respectively.

A total of 104 SFI active components were obtained, of which 29 targeted 76 genes. After intersecting with 3370 AP-related genes, 42 SFI treatment AP potential targets were identified. Enrichment analysis revealed that these targets were associated with cell apoptosis, necroptosis, and multiple signal transduction pathways, such as p53, IL-17 and TNF signal pathways, etc. Molecular docking demonstrated that the active components of SFI had good binding affinity with the corresponding targets and the binding ability of NGF and aromadendrene was the strongest. Bioinformatics analysis revealed that SFI treatment in AP is associated with various cell types, including acinar cells, endothelial cells, T cells, dendritic cells, ductal cells, and mesenchymal cells. Furthermore, in vitro experiments demonstrated that SFI induces acinar cell apoptosis in a dose-dependent manner, accompanied by increased expression of cleaved-caspase3/caspase3 and cleaved-caspase8/caspase8 proteins, and inhibition of inflammatory cytokine (TNF-ɑ, IL-1β, and PTGS2) expression. In vivo experiments demonstrated that SFI improved histopathological alterations, reduces inflammation, and promotes apoptosis and the expression of cleaved-casp3 and cleaved-casp8 in AP rats.

This study elucidated the multi-component, multi-target, and multi-cellular characteristics of SFI in the treatment of AP, and confirmed its mechanism of promoting acinar cell apoptosis.

Introduction: Acute necrotizing pancreatitis (ANP) is the acute inflammation of pancreatic parenchyma, most commonly due to alcohol abuse or cholelithiasis. The treatment can be either conservative or invasive, including a variety of techniques; however, it has not yet been established if the intervention should be early or if it should be delayed. The aim of this review is to investigate the optimal time for intervention in ANP. Methods: A literature search was conducted in PubMed and Scopus from inception until September 2024 for studies reporting the comparison between early and late intervention. Results: Early intervention, within 4 weeks of symptom onset, often involves drainage via percutaneous, endoscopic, or combined methods. Delayed intervention occurs after 4 weeks of symptom onset. This can be conducted either surgically or via minimally invasive means. The results of this review reveal that the time of intervention for ANP plays an important role in the prognosis and the course of the disease. In particular, early intervention is associated with higher mortality, which is also the primary clinical outcome. Delayed intervention is also superior regarding secondary clinical outcomes, specifically the complications associated with the intervention. Thus, it is accompanied by fewer episodes of new-onset organ failure, bleeding, gastrointestinal fistula, pancreatic fistula, wound infection, endocrine pancreatic insufficiency, and other complications. Finally, delayed intervention results in shorter stays, both in hospitals and the ICU. Conclusions: Delayed intervention is clearly more effective than early intervention and should be preferred. However, early intervention appears to be both safe and effective, and it is feasible.

Dahuang Mudan Decoction is commonly used in China for the treatment of acute pancreatitis. Nevertheless, the therapeutic efficacy of the drug remains a subject of debate, and its active ingredients and potential therapeutic targets remain to be determined. The present study used a network pharmacological approach to investigate the active ingredients and possible targets of the drug, and illustrated the clinical effectiveness of Dahuang Mudan Decoction in the treatment of acute pancreatitis by meta-analysis.

The present study investigated the active ingredients of the constituent herbs of Dahuang Mudan Decoction using the TCMID database. In order to further identify molecular targets, Swiss Target Prediction, OMIM and Genecards databases was be used. The present study used metascape database for gene ontology function enrichment analysis and Kyoto Genome Encyclopedia pathway enrichment analysis. A gene interaction network diagram was established for predicting the main targets and mechanism of action to Dahuang Mudan Decoction for acute pancreatitis. To further illustrate the validity of the gene targets and the clinical efficacy of the drug, 13 relevant studies were included for meta-analysis and analyzed using the Cochrane Collaboration's Review Manager 5.4 software.

After a thorough screening process, the present study identified three main components of Dahuang Mudan Decoction: kaempferol, quercetin and eupatin. These three major components have the potential to target 5 important proteins: AKT1, TNF-a, IL-6, TP53, HIF1A. In addition, pathway analyses by the Kyoto Genome Encyclopedia showed that Dahuang Mudan Decoction is active through the Pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, etc signaling pathway to act on acute pancreatitis. The results of meta-analysis showed that compared with the control group, the experimental group had superior performance in terms of overall treatment efficacy, reduction of hospital stays and inflammatory factor levels after treatment.

In summary, network pharmacological studies have shown that Dahuang Mudan Decoction affects acute pancreatitis through different components, targets, and mechanisms. In addition, the meta-analysis study strongly supported the effectiveness of Dahuang Mudan Decoction in the treatment of acute pancreatitis.

Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on cerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood.

A cerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of cerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules.

We found that exosomes derived from cerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in cerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells.

Exosomes derived from cerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

The occurrence of pancreatitis shortly after elective lumbar spine surgery in an adult is rare. We report a case of a 63-year-old female who developed, for the first time, acute pancreatitis within three days of elective lumbar (L) spine surgery that was performed for degenerative disk disease without significant deformity (i.e., no scoliosis or spondylolisthesis). The surgery was conducted using a lateral transpsoas approach and included interbody fusions at L3-L4 and L4-L5 levels and posterior instrumentation with pedicle screws and rods. Ten years prior, she had a cholecystectomy, and she was not diabetic or obese. She began experiencing significant nausea and malaise two days after that lumbar spine surgery, requiring hospitalization on the third postoperative day. Her pancreatitis became chronic, and a large pancreatic pseudocyst developed and persisted despite using an external drainage catheter for 52 days. At 126 days after the spinal surgery, an open Roux-en-Y pancreatic cystojejunostomy was performed to internally drain the cyst, which had enlarged to 19 cm. Significant pre-surgical risk factors for this first-time case of pancreatitis were not identified. The spine surgeon denied iatrogenic causes such as instrument plunging or complications associated with the use of a "lateral access retraction system," and surgical blood loss was only 50 ml during the elective lumbar spine surgery. However, during the lumbar spine surgery, hypotension occurred for 20 minutes (mean arterial pressure: 63-73 mmHg), which was associated with transient acute kidney injury. This might have contributed to the development of her pancreatitis because the pancreas is more sensitive to ischemia than the kidney. During the initial week after the onset of pancreatitis, her symptoms were mainly believed to be due to an acute postoperative infection. However, there was no growth in cultures from aspirations of the pleural effusion, retroperitoneal effusion, and deeper incision area. Despite extensive workup, the cause of the patient's pancreatitis was not determined. We report this case not only because of its rarity but also to help surgeons and other healthcare providers in the workup and management of similar situations.

To date, the association between glucocorticoid use and the risk of pancreatitis remains controversial. The aim of this study was the investigation of this possible relationship.

We carried out a two-sample Mendelian randomization (MR) analysis using GWAS data from European ancestry, East Asian descendants and the FinnGen Biobank Consortium to evaluate this potential causal relationship. Genetic variants associated with glucocorticoid use were selected based on genome-wide significance (p < 5×10-8).

Our MR analysis of European ancestry data revealed no significant causal relationship between glucocorticoid use and AP (IVW: OR=1.084, 95% CI= 0.945-1.242, P=0.249; MR-Egger: OR=1.049, 95% CI= 0.686-1.603, P=0.828; weighted median: OR=1.026, 95% CI= 0.863-1.219, P=0.775) or CP (IVW: OR=1.027, 95% CI= 0.850-1.240, P=0.785; MR-Egger: OR= 1.625, 95% CI= 0.913-2.890, P= 0.111; weighted median: OR= 1.176, 95% CI= 0.909-1.523, P= 0.218). Sensitivity analyses, including MR-Egger and MR-PRESSO, indicated no evidence of pleiotropy or heterogeneity, confirming the robustness of our findings. Multivariable MR analysis adjusted for alcohol consumption, BMI, cholelithiasis and C-reactive protein levels supported these findings. Replicated analysis was performed on datasets from the FinnGen Biobank Consortium and East Asian descendants, and similar results were obtained.

This MR analysis suggests that there is no causal association between glucocorticoid use and the risk of pancreatitis.

There is lack of data on the association between socioeconomic factors, guidelines compliance and clinical outcomes among patients with acute biliary pancreatitis (ABP).

Post-hoc analysis of the international MANCTRA-1 registry evaluating the impact of regional disparities as indicated by the Human Development Index (HDI), and guideline compliance on ABP clinical outcomes. Multivariable logistic regression models were employed to identify prognostic factors associated with mortality and readmission.

Among 5313 individuals from 151 centres across 42 countries marked disparities in comorbid conditions, ABP severity, and medical procedure usage were observed. Patients from lower HDI countries had higher guideline non-compliance (p < 0.001) and mortality (5.0% vs. 3.2%, p = 0.019) in comparison with very high HDI countries. On adjusted analysis, ASA score (OR 1.810, p = 0.037), severe ABP (OR 2.735, p < 0.001), infected necrosis (OR 2.225, p = 0.006), organ failure (OR 4.511, p = 0.001) and guideline non-compliance (OR 2.554, p = 0.002 and OR 2.178, p = 0.015) were associated with increased mortality. HDI was a critical socio-economic factor affecting both mortality (OR 2.452, p = 0.007) and readmission (OR 1.542, p = 0.046).

These data highlight the importance of collaborative research to characterise challenges and disparities in global ABP management. Less developed regions with lower HDI scores showed lower adherence to clinical guidelines and higher rates of mortality and recurrence.

Gallstone pancreatitis (GSP) is the leading cause of acute pancreatitis, accounting for approximately 50% of cases. Without appropriate and timely treatment, patients are at increased risk of disease progression and recurrence. While there is increasing consensus among guidelines for the management of mild GSP, adherence to these guidelines remains poor. In addition, there is minimal evidence to guide clinicians in the treatment of moderately severe and severe pancreatitis.

The management of GSP continues to evolve and is dependent on severity of acute pancreatitis and concomitant biliary diagnoses. Across the spectrum of severity, there is evidence that goal-directed, moderate fluid resuscitation decreases the risk of fluid overload and mortality compared with aggressive resuscitation. Patients with isolated, mild GSP should undergo same-admission cholecystectomy; early cholecystectomy within 48 hours of admission has been supported by several randomized clinical trials. Cholecystectomy should be delayed for patients with severe disease; for severe and moderately severe disease, the optimal timing remains unclear. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) is only useful for patients with suspected cholangitis or biliary obstruction, although the concomitance of these conditions in patients with GSP is rare. Modality of evaluation of the common bile duct to rule out concomitant choledocholithiasis varies and should be tailored to level of concern based on objective measures, such as laboratory results and imaging findings. Among these modalities, intraoperative cholangiography is associated with reduced length of stay and decreased use of ERCP. However, the benefit of routine intraoperative cholangiography remains in question.

Treatment of GSP is dependent on disease severity, which can be difficult to assess. A comprehensive review of clinically relevant evidence and recommendations on GSP severity grading, fluid resuscitation, timing of cholecystectomy, need for ERCP, and evaluation and management of persistent choledocholithiasis can help guide clinicians in diagnosis and management.

The primary objective of this study is to comparatively assess the safety of nasogastric (NG) feeding versus nasojejunal (NJ) feeding in patients with acute pancreatitis (AP), with a special focus on the initiation of these feeding methods within the first 48 h of hospital admission.

Studies were identified through a systematic search in PubMed, EMbase, Cochrane Central Register of Controlled Trials, and Web of Science. Four studies involving 217 patients were included. This systematic review assesses the safety and efficacy of nasogastric versus nasojejunal feeding initiated within 48 h post-admission in moderate/severe acute pancreatitis, with a specific focus on the timing of initiation and patient age as influential factors.

The results showed that the mortality rates were similar between NG and NJ feeding groups (RR 0.86, 95% CI 0.42 to 1.77, P = 0.68). Significant differences were observed in the incidence of diarrhea (RR 2.75, 95% CI 1.21 to 6.25, P = 0.02) and pain (RR 2.91, 95% CI 1.50 to 5.64, P = 0.002) in the NG group. The NG group also showed a higher probability of infection (6.67% vs. 3.33%, P = 0.027) and a higher frequency of multiple organ failures. Subgroup analysis for early intervention (within 48 h) showed a higher risk of diarrhea in the NG group (RR 2.80, P = 0.02). No significant differences were found in the need for surgical intervention, parenteral nutrition, or success rates of feeding procedures.

This meta-analysis highlights the importance of considering the method and timing of nutritional support in acute pancreatitis. While NG feeding within 48 h of admission increases the risk of certain complications such as diarrhea and infection, it does not significantly impact mortality or the need for surgical intervention.

Acute pancreatitis is a common and potentially life-threatening condition. It is characterized by inflammation of the pancreas, most often leading to elevated levels of pancreatic enzymes in the blood. In a subset of patients, however, conventional biomarker levels may remain within the reference range. Such instances have the potential to create a diagnostic challenge for healthcare professionals and can lead to misdiagnosis or delayed treatment. This article presents the intriguing clinical scenario of acute pancreatitis with normal amylase and lipase, discusses factors that may lead to normoenzymatic presentation, and reminds clinicians of the diagnostic criteria for acute pancreatitis, which does not necessarily require elevated pancreatic enzymes.

To investigate the effect of honokiol (HON) and the role of high-mobility group protein B1 (HMGB1) on the pathogenesis of severe acute pancreatitis (SAP).

Thirty mice were numbered according to weight, and randomly divided into 5 groups using a random number table, including control, SAP, SAP and normal saline (SAP+NS), SAP and ethyl pyruvate (SAP+EP), or SAP+HON groups, 6 mice in each group. Samples of pancreas, intestine, and blood were collected 12 h after SAP model induction for examination of pathologic changes, immune function alterations by enzyme linked immunosorbent assay (ELISA), and Western blot. In vitro experiments, macrophages were divided into 5 groups, the control, lipopolysaccharide (LPS), LPS+DMSO (DMSO), LPS+anti-HMGB1 monoclonal antibody (mAb), and LPS+ HON groups. The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled. The location and acetylation of HMGB1 were measured by Western blot. Finally, pyridone 6 and silencing signal transducer and activator of the transcription 1 (siSTAT1) combined with honokiol were added to determine whether the Janus kinase (JAK)/ STAT1 participated in the regulation of honokiol on HMGB1. The protein expression levels of HMGB1, JAK, and STAT1 were detected using Western blot.

Mice with SAP had inflammatory injury in the pancreas, bleeding of intestinal tissues, and cells with disrupted histology. Mice in the SAP+HON group had significantly fewer pathological changes. Mice with SAP also had significant increases in the serum levels of amylase, lipase, HMGB1, tumor necrosis factor- α, interleukin-6, diamine oxidase, endotoxin-1, and procalcitonin. Mice in the SAP+HON group did not show these abnormalities (P<0.01). Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability, decreased the levels of junctional adhesion molecule C, and elevated intercellular permeability (P<0.01). HON treatment blocked these effects. Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1, however, HON treatment increased the nuclear level of HMGB1 (P<0.01). HON treatment also inhibited the expressions of JAK1, JAK2, and STAT1 (P<0.01) and increased the acetylation of HMGB1 (P<0.05).

HON prevented intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway.

Acute pancreatitis is a major disease that endangers the health and lives of people. Historically, clinical therapy has recommended. that patients with acute pancreatitis remain nil by mouth. As one of the therapies recommended in recent guidelines, early enteral nutrition support reduces the incidence of infectious complications and reduces the risk of severe conditions. However, early enteral nutrition support has not been optimally implemented within clinical practice for acute pancreatitis inpatients.

This evidence implementation project aimed to increase compliance with best practice recommendations for early enteral nutrition support, while standardizing the enteral nutrition support process and reducing the incidence of delayed enteral nutrition.

The project was guided by the JBI Evidence Implementation Framework, which is grounded in the audit and feedback process, as well as a seven-stage structured approach to identifying and managing barriers to compliance with recommended practices.

In the baseline audit, compliance rates were low for all evidence-based audit criteria. Four of the eight criteria showed 0% compliance. However, after implementation, all eight criteria achieved a minimum compliance rate of 60%, with Site 2 achieving 90% to 100% compliance. In addition, nurses improved their knowledge and skills in early enteral nutrition support. The incidence of delayed enteral nutrition also fell from 86.2% to 20.7% at both study sites. The implementation strategy included a training program, psychological interventions, and financial and human resource support.

This project not only significantly improved early enteral nutrition support for acute pancreatitis patients, but also increased nurses' knowledge and practice skills, standardized the process of enteral nutrition support, and reduced the incidence of delayed enteral nutrition.

http://links.lww.com/IJEBH/A177.

To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge., (Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis (AP) using a network pharmacology approach and validate the findings in animal experiments.

Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation. Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry, Western blot analysis and real-time quantitative PCR, respectively.

Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3 (MAPK3), Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), protein c-Fos (FOS) were identified as core targets in the protein interaction (PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone II and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation (P<0.01).

DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues, which would be functioned by regulating Th17 cell differentiation-related mRNA and protein expressions.

Acute pancreatitis (AP) is a potentially lethal acute disease highly involved in coagulation disorders. Pyroptosis has been reported to exacerbate coagulation disorders, yet this implication has not been illustrated completely in AP.

RNA sequencing data of peripheral blood of AP patients were downloaded from the Gene Expression Omnibus database. Gene set variation analysis and single sample gene set enrichment analysis were used to calculate the enrichment score of coagulation-related signatures and pyroptosis. Spearman and Pearson correlation analysis was used for correlation analysis. Peripheral blood samples and related clinical parameters were collected from patients with AP and healthy individuals. A severe AP (SAP) model of mice was established using caerulein and lipopolysaccharide. Enzyme-linked immunosorbent assay, chemiluminescence immunoassay and immunohistochemical analysis were employed to detect the level of coagulation indicators and pyroptosis markers in serum and pancreas tissues. Additionally, we evaluated the effect of pyroptosis inhibition and NLRC4 silence on the function of human umbilical vein endothelial cells (HUVECs).

Coagulation disorders were significantly positively correlated to the severity of AP, and they could be a predictor for AP severity. Further analyses indicated that six genes-DOCK9, GATA3, FCER1G, NLRC4, C1QB and C1QC-may be involved in coagulation disorders of AP. Among them, NLRC4 was positively related to pyroptosis that had a positive association with most coagulation-related signatures. Data from patients showed that NLRC4 and other pyroptosis markers, including IL-1β, IL-18, caspase1 and GSDMD, were significant correlation to AP severity. In addition, NLRC4 was positively associated with coagulation indicators in AP patients. Data from mice showed that NLRC4 was increased in the pancreas tissues of SAP mice. Treatment with a pyroptosis inhibitor effectively alleviated SAP and coagulation disorders in mice. Finally, inhibiting pyroptosis or silencing NLRC4 could relieve endothelial dysfunction in HUVECs.

NLRC4-mediated pyroptosis damages the function of endothelial cells and thereby exacerbates coagulation disorders of AP. Inhibiting pyroptosis could improve coagulation function and alleviate AP.

Acute pancreatitis is a rare disease in pregnant patients. Although it may have serious maternal and fetal consequences, morbidity and mortality rates have decreased recently due to appropriate and rapid treatment with earlier diagnosis. The aim of this study was to evaluate pregnant patients diagnosed with acute pancreatitis.

The study included pregnant patients diagnosed with acute pancreatitis who were admitted to Adana City Training and Research Hospital in Adana, Turkey, between January 2014 and January 2022. Patients' files were screened. Patients' demographics, acute pancreatitis etiology, severity, complications, and applied treatment, as well as maternal and fetal outcomes were evaluated.

The study included 65 pregnant patients with acute pancreatitis. The mean age was 26.6±5 (19-41) years. Acute pancreatitis was observed in the third trimester. The most common cause of acute pancreatitis was gallstones, and its severity was often mild. Only two patients required endoscopic retrograde cholangiopancreatography, and the remaining patients were treated medically. Maternal and infant death developed in a patient with necrotizing acute pancreatitis secondary to hyperlipidemia.

The most common etiology of acute pancreatitis in pregnancy was gallstones. Acute pancreatitis occurred in the third trimester. Most of the patients had mild acute pancreatitis. Maternal and fetal complications were rare. We think that the reasons for the low mortality rate were mild disease severity and biliary etiology, and most patients were in the third trimester, as well as early diagnosis and no delay in the intervention.

Acute pancreatitis is one of the main reasons for digestive admissions. Adequate pain treatment is crucial in its management. However, there are hardly any descriptions of the analgesic guidelines used in our setting.

On-line survey on analgesic management in acute pancreatitis, aimed at attending physicians and residents practising in Spain.

Two hundred and nine physicians from 88 centres responded to the survey. Ninety percent were specialists in gastrointestinal medicine and 69% worked in a tertiary centre. The majority (64.4%) do not routinely use scales to measure pain. When choosing a drug, experience in its use was the most important factor. The most commonly prescribed initial treatments are: combination of paracetamol and metamizole (53.5%), paracetamol alone (19.1%) and metamizole alone (17.4%). As rescue: meperidine (54.8%), tramadol (17.8%), morphine chloride (17.8%) and metamizole (11.5%). Continuous perfusion is used in 8.2% of initial treatments. Physicians with >10 years of service use more metamizole as monotherapy (50%), while residents and attending physicians with <10 years of service prescribe it in combination with paracetamol (85%). If progression is needed, morphine chloride and meperidine are mainly used. The speciality of the respondent, the size of the work centre and the unit/service where the patients were admitted did not influence the analgesia prescribed. Satisfaction with pain management reached 7.8/10 (SD 0.98).

In our setting, metamizole and paracetamol are the most commonly used analgesics as initial pain treatment in acute pancreatitis, and meperidine is the most commonly used rescue analgesic.

Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and viral infections. Recent studies have illuminated the emergence of vaccine-induced acute pancreatitis, notably associated with COVID-19 vaccinations, presenting diverse mechanisms ranging from direct viral-mediated injury to autoimmune reactions. Understanding this link is pivotal for public health, yet challenges persist in identifying and managing cases post-vaccination. Comprehensive literature reviews employing the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement outline the potential pathways and mechanisms leading to vaccine-induced pancreatitis, emphasizing the need for deeper investigations into underlying health conditions and modifications to vaccine components. Notably, the rare occurrences of vaccine-induced pancreatitis extend beyond COVID-19 vaccines, with reports also documenting associations with measles, mumps, and rubella (MMR), human papillomavirus (HPV), and other viral vaccinations. Mechanistically, hypotheses such as molecular mimicry and immunologic injury have been proposed, necessitating ongoing vigilance and exploration. Regulatory agencies play a crucial role in monitoring and communicating vaccine safety concerns, emphasizing transparency to address potential risks and maintain public trust. Understanding and communicating these rare adverse events with transparency remain integral for informed vaccination policies and to allay concerns surrounding vaccine safety.

To compare factor(s) contributing to aetiology, management and clinical outcome(s) of paediatric patients acquiring acute pancreatitis (AP) at two major university paediatric surgical centres in Liverpool and Bangkok.

All patients (<18 years) with an index diagnosis of AP (ICD 10 coding) during 2006-2016 were studied.

121 patients included n = 79 (65.3%) in Thailand versus n = 42 (34.7%) in the UK centre with no difference(s) in age at diagnosis at 10.4 ± 4.5 and 11.7 ± 6 years. (P = 0.12). Major AP aetiology(s) in Thailand were medications (39.2%) and choledochal cysts (8.9%). In the UK-gallstone disease (21.4%), and medications (16.7%) were leading factors (P < 0.01). Ultrasonography was deployed more frequently in the UK versus Thai centre (74.3% vs. 49.1%; P < 0.01). Pancreatitis was confirmed by imaging in 67.9% (Thai) and 62.9% (UK) patients (P = 0.47). Most patients at both centres had a mild-grade pancreatitis illness (95% Thai vs. 90.5% UK; P = 0.28) while 12.7% of Thai and 19% of UK children developed pancreatitis-related complication (P = 0.37). Overall mortality rate (%) was significantly higher in the Thai versus UK centre (27.8% vs. 9.5%; P = 0.02).

Aetiology of acute pancreatitis appears to vary between UK and Thailand children. Timely early diagnosis and healthcare pathways may be driven by local patient-related factor(s). The higher mortality (%) observed in Thailand versus UK in this comparative study was linked to underlying co-existent chronic medical condition(s) in vulnerable patient cohorts.

Acute pancreatitis (AP) is a common inflammatory response that occurs in the pancreas with mortality rates as high as 30 %. However, there is still no consistent and effective treatment for AP now. MicroRNA-148 was reported to be involved in AP through IL-6 signaling pathway. Therefore, we aimed to further explore the detailed mechanisms of AP, to develop more therapeutic approach for AP. Exosomes were isolated from peripheral blood mononuclear cells of 20 AP patients and 20 healthy volunteers to evaluate the abnormally expressed miRNA. Then pancreatic acinar cells (PACs) were transfected with retrovirus to overexpress miR-148a/miR-551b-5p to evaluate their function. Both miR-148a and miR-551b-5p were highly expressed in AP patients than these in healthy cases. Then overexpressing miR-551b-5p in PACs could regulate autophagy through directly binding to Baculoviral IAP Repeat Containing 6, leading to the increased secretions of interleukin-1β (IL-1β) and interleukin-18 (IL-18) through interleukin-1 (IL-1) signaling pathway. Moreover, overexpressing miR-148a in PACs could decrease the secretions of IL-1β and IL-18 to modulate autophagy. The exosomal miRNA-148a and miRNA-551b-5p derived from peripheral blood mononuclear cells of AP patients may two-way mediate autophagy damage through IL-6/STAT3 signaling pathway, which participated in the AP pathogenesis. Our findings may provide new targets for the diagnosis and treatment of AP.

Acute kidney injury (AKI) represents a frequent and grave complication associated with acute pancreatitis (AP), substantially elevating both mortality rates and the financial burden of hospitalization. The aim of our study is to construct a predictive model utilizing automated machine learning (AutoML) algorithms for the early prediction of AKI in patients with AP.

We retrospectively analyzed patients who were diagnosed with AP in our hospital from January 2017 to December 2021. These patients were randomly allocated into a training set and a validation set at a ratio of 7:3. To develop predictive models for each set, we employed the least absolute shrinkage and selection operator (LASSO) algorithm along with AutoML. A nomogram was developed based on multivariate logistic regression analysis outcomes. The model's efficacy was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Additionally, the performance of the model constructed via AutoML was evaluated using decision curve analysis (DCA), feature importance, SHapley Additive exPlanations (SHAP) plots, and locally interpretable model-agnostic explanations (LIME).

This study incorporated a total of 437 patients who met the inclusion criteria. Out of these, 313 were assigned to the training cohort and 124 to the validation cohort. In the training and validation cohorts, AKI occurred in 68 (21.7%) and 29(23.4%) patients, respectively. Comparative analysis revealed that the AutoML models exhibited enhanced performance over traditional logistic regression (LR). Furthermore, the deep learning (DL) model demonstrated superior predictive accuracy, evidenced by an area under the ROC curve of 0.963 in the training set and 0.830 in the validation set, surpassing other comparative models. The key variables identified as significant in the DL model within the training dataset included creatinine (Cr), urea (Urea), international normalized ratio (INR), etiology, smoking, alanine aminotransferase (ALT), hypertension, prothrombin time (PT), lactate dehydrogenase (LDH), and diabetes.

The AutoML model, utilizing DL algorithm, offers considerable clinical significance in the early detection of AKI among patients with AP.

Acute pancreatitis is an acute inflammation of the pancreas, with subsequent involvement of surrounding tissues and organ systems. Viral etiology of acute pancreatitis is uncommon; however, multiple viruses have been implicated. Dengue virus has also been found responsible for acute pancreatitis, with possible etiologies linked to direct viral invasion, autoimmune mechanism, or as a complication of dengue shock syndrome. We present a case of a 24-year-old female who presented with epigastric pain and vomiting in the background of a febrile illness and was later diagnosed with mild acute pancreatitis complicating dengue fever.

The goal of this study was to investigate the clinical value of emergent triglyceride (TG)-lowering therapies for hyperlipidemic acute pancreatitis (HLAP).

126 HLAP patients were assigned randomly to receive either conventional treatment (CT), normal saline (NS) alone, or continuous veno-venous hemofiltration (CVVH) as an intensive TG-lowering therapy. TG levels, clinical outcomes, and inflammatory biomarkers were compared among the three groups.

Baseline characteristics did not differ significantly among the groups. CVVH removed TG from the plasma and achieved its target TG (<500 mg/dL) in approximately 25 h, compared to 40 h in the NS alone group and no targeted effect within 48 h in the CT group (P < 0.05). Although the majority of clinical outcomes did not differ significantly, an unexpectedly higher incidence of organ failure occurred in the CVVH group compared to the others. Hospital costs, severe AP patients and length of stay were significantly higher in the CVVH group compared to the other groups (P < 0.005).

Early CVVH lowers TG levels more efficiently than NS alone or CT therapy, but is not superior in terms of clinical outcomes and costs. NS also lowers TG levels and is significantly less costly than the other two treatments. Further multicenter studies are needed to determine the feasibility of NS alone treatment for HLAP patients.

The relationship between total cholesterol (TC) levels and the severity of hypertriglyceridemic acute pancreatitis (HTGAP) remains unclear.

The aim of this study was to investigate the relationship between the levels of TC at admission with the severity of HTGAP, in order to apply it as a reliable predictor at early stage in clinical practice.

We performed a cohort study including 249 patients with AHTGP between November 2012 and April 2022 in XuanWu Hospital. Fasting TC was assayed within 24 h of admission, age, gender, body mass index, hypertension, diabetes mellitus, drinking, smoking, neutrophil-lymphocyte ratio, C-reactive protein and glucose were recorded as confounding factors. To evaluate the relationship of TC and the severity of HTGAP, we used smooth curve fitting and a segmented regression model with adjustment of confounding factors to analyze the threshold effect between TC and SAP occurrence risk.

249 Patients were enrolled. The incidence of SAP was 25.3% (63/249). A nonlinear relationship between TC level and the severity of HTGAP. 6.09 mmol/L was the optimal TC value associated with the lowest risk of SAP occurrence. Moreover, TC level was negatively correlated with risk of severe HTGAP occurrence for TC < 6.09 mmol/L (OR 0.45, 95% CI 0.23-0.85, P = 0.014) and positively correlated for TC > 6.09 mmol/L in HTGAP patients (OR 1.14, 95% CI 1.04-1.26, P = 0.006).

We found that serum TC level is nonlinearly associated with the severity of HTGAP, and it can be a reliable predictor for early intervention and intensive care.

Gallstone disease will affect 15% of the adult population with concomitant common bile duct stone (CBDS) occurring in up to 30%. Endoscopic retrograde cholangiopancreatography (ERCP) is the mainstay of management for removal of CBDS, as cholecystectomy for the prevention of recurrent biliary event (RBE). RBE occurs in up to 47% if cholecystectomy is not done. The goal of this study was to evaluate the timing of occurrence of RBE after common bile duct clearance with ERCP and associated outcomes.

The records of all patients who underwent ERCP for gallstone disease followed by cholecystectomy, in a single center from 2010 to 2022, were reviewed. All RBE were identified. Actuarial incidence of RBE was built. Patients with and without RBE were compared.

The study population is composed of 529 patients. Mean age was 58.0 (18-95). There were 221 RBE in 151 patients (28.5%), 39/151 (25.8%) having more than one episode. The most frequent RBE was acute cholecystitis (n = 104) followed by recurrent CBDS (n = 95). Median time for first RBE was 34 days. Actuarial incidence of RBE started from 2.5% at 7 days to reach 53.3% at 1 year. Incidence-rate of RBE was 2.9 per 100 person-months. Patients with RBE had significant longer hospitalisation time (11.7 vs 6.4 days; P < 0.0001), longer operative time (66 vs 48 min; P < 0.0001), longer postoperative stay (2.9 vs 0.9 days; P < 0.0001), higher open surgery rate (7.9% vs 1.3%; P < 0.0001), and more complicated pathology (23.8% vs 5.8%; P < 0.0001) and cholecystitis (64.2% vs 25.9%; P < 0.0001) as final diagnoses.

RBE occurred in 28.5% of the subjects at a median time of 34 days, with an incidence of 2.5% as early as 1 week. Cholecystectomy should be done preferably within 7 days after common bile duct clearance in order to prevent RBE and adverse outcomes.

Acute pancreatitis is a common condition of the digestive system, but sometimes it develops into severe cases. In about 10-20% of patients, necrosis of the pancreas or its periphery occurs. Although most have aseptic necrosis, 30% of cases will develop infectious necrotizing pancreatitis. Infected necrotizing pancreatitis (INP) requires a critical treatment approach. Minimally invasive surgical approach (MIS) and endoscopy are the management methods. This meta-analysis compares the outcomes of MIS and endoscopic treatments.

We searched a medical database until December 2022 to compare the results of endoscopic and MIS procedures for INP. We selected eligible randomized controlled trials (RCTs) that reported treatment complications for the meta-analysis.

Five RCTs comparing a total of 284 patients were included in the meta-analysis. Among them, 139 patients underwent MIS, while 145 underwent endoscopic procedures. The results showed significant differences (p < 0.05) in the risk ratios (RRs) for major complications (RR: 0.69, 95% confidence interval (CI): 0.49-0.97), new onset of organ failure (RR: 0.29, 95% CI: 0.11-0.82), surgical site infection (RR: 0.26, 95% CI: 0.07-0.92), fistula or perforation (RR: 0.27, 95% CI: 0.12-0.64), and pancreatic fistula (RR: 0.14, 95% CI: 0.05-0.45). The hospital stay was significantly shorter for the endoscopic group compared to the MIS group, with a mean difference of 6.74 days (95% CI: -12.94 to -0.54). There were no significant differences (p > 0.05) in the RR for death, bleeding, incisional hernia, percutaneous drainage, pancreatic endocrine deficiency, pancreatic exocrine deficiency, or the need for enzyme use.

Endoscopic management of INP performs better compared to surgical treatment due to its lower complication rate and higher patient life quality.