BACKGROUND: With respect to severity and outcome of an index episode of idiopathic acute pancreatitis the current literature reports conflicting retrospective results. One reason might be the retrospective study design precluding in depth analysis resulting in mixed etiologies and combination of index episode versus recurrent idiopathic acute pancreatitis.
METHODS: In this retrospective monocentric cohort study, we retrieved all patients with a first acute pancreatitis episode treated between 2005 and 2021 at the LMU University Hospital from our clinical information system based on the respective ICD-10 codes. In an initial sample of 1390 presumed idiopathic pancreatitis patients we identified 68 confirmed idiopathic acute pancreatitis patients and compared those to 75 first-time alcohol-induced acute pancreatitis patients and 390 first-time biliary-induced acute pancreatitis patients. Clinical outcome (severity, SIRS, mortality, and re-admission rate) was set as outcome measures. Multinomial logistic regression analysis was performed.
RESULTS: In alcohol-induced acute pancreatitis moderate and severe courses occur significantly more often when compared to idiopathic acute pancreatitis (17.33 % vs. 10.29 %; multinomial logistic regression p = 0.0021). There were no significant differences in mortality between first-time alcoholic, idiopathic and biliary pancreatitis (p = 0.6328). Patients with idiopathic acute pancreatitis had significantly more hospital readmissions (within 30 days) compared to alcohol-induced pancreatitis patients (p = 0.0284).
CONCLUSIONS: In the context of a first episode of acute pancreatitis, idiopathic acute pancreatitis remains a challenging diagnosis posing an increased risk of recurrence, but not an increased risk for a more severe disease course.

The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). Via Visium spatial transcriptomics, eight distinct tissue clusters were revealed from aggregated transcriptomes of aging and young AAP mice: five acinar, two stromal, and one islet, which were then merged into three clusters: acinar, stromal, and islet for the comparative analysis. Compared to young AAP mice, > 1300 differentially expressed genes (DEGs) and approximately 3000 differentially regulated pathways were identified in aging AAP mice. The top five DEGs upregulated in aging AAP mice include Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp with heterogeneous distributions among the clusters. Taken together, this study demonstrates spatial heterogeneity of inflammatory processes in aging AAP mice, offering novel insights into the mechanisms and potential drivers for AAP development. KEY MESSAGES: Mechanisms regarding high mortality of AAP in aging remain undefined. An aging AAP mouse model was developed recapturing clinical exhibition in humans. Spatial transcriptomics identified contrasted DEGs in aging vs. young AAP mice. Top five DEGs were Mmp8, Ppbp, Serpina3m, Cxcl13, and Hamp in aging vs. young AAP mice. Our findings shed insights for identification of molecular drivers in aging AAP.

BACKGROUND: Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis.
METHODS: Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up.
RESULTS: A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0-42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038).
CONCLUSIONS: Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.

Given the paucity of interventions to treat pancreatitis, it is imperative to identify and intervene upon modifiable risk factors such as heavy alcohol use. Current trends indicate a concerning increase in alcohol misuse and alcohol-related disease since the onset of the coronavirus disease-2019 pandemic.1 The incidence of pancreatitis associated with alcohol misuse has increased by approximately 3% annually from 1961 to 2016.2 Alcohol recidivism may be the most important risk factor for pancreatitis recurrence and development of chronic pancreatitis in the United States.3 Early identification of alcohol misuse as a modifiable risk factor is paramount to mitigating pancreatitis-related morbidity. However, blood ethanol and urine ethyl glucuronide levels may be low in symptomatic individuals because they clear rapidly and patients may abstain from drinking in the days before their clinical presentation. Patient self-report may underestimate the quantity of alcohol intake and falsely reassure the provider that this is not a contributing factor to the presentation.4.

暂无摘要。

BACKGROUND: The worldwide incidence of acute pancreatitis (AP) is increasing, but the dominant etiology of AP may vary by country. Mixed etiologies are involved in the increase in the number of AP patients.
OBJECTIVE: This study was to analyze the etiological changes and prognosis of AP patients and explore the prognosis of AP patients with mixed etiologies.
METHODS: Using a retrospective analysis method, AP patients hospitalized from January 2007 to December 2021 were selected from a pancreatic center in Nanchang, China. Trends in the main etiologies were analyzed, and the severity and prognosis of different etiologies were compared.
RESULTS: A total of 10,071 patients were included. Cholelithiasis (56.0%), hyperlipidemia (25.3%), and alcohol (6.5%) were the top three etiologies. The proportion of acute biliary pancreatitis (ABP) showed a decreasing trend, while the proportion of hypertriglyceridemic pancreatitis (HTGP) and alcoholic AP showed an increasing trend (all ptrend < 0.001). The incidence of organ failure and necrotizing pancreatitis was higher in patients with HTGP than in those with AP induced by other etiologies (all p < 0.05). There was no statistically significant difference in mortality among patients with different etiologies. Patients with AP due to a mixed hypertriglyceridemia-alcoholic etiology had higher ICU admission rates and were more severe than those with AP induced by other mixed etiologies.
CONCLUSIONS: In the past 15 years, the proportion of ABP has trended downward, while those of HTGP and alcoholic AP have risen. Among patients with mixed etiologies, those with a mixed hypertriglyceridemia-alcoholic etiology had a worse prognosis.

OBJECTIVE: The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend any specific treatment strategy regarding alcohol cessation. The PANDA trial investigates whether implementation of a structured alcohol cessation support program prevents pancreatitis recurrence after a first episode of acute alcoholic pancreatitis.
METHODS: PANDA is a nationwide cluster randomised superiority trial. Participating hospitals are randomised for the investigational management, consisting of a structured alcohol cessation support program, or current practice. Patients with a first episode of acute pancreatitis caused by harmful drinking (AUDIT score >7 and < 16 for men and >6 and < 14 for women) will be included. The primary endpoint is recurrence of acute pancreatitis. Secondary endpoints include cessation or reduction of alcohol use, other alcohol-related diseases, mortality, quality of life, quality-adjusted life years (QALYs) and costs. The follow-up period comprises one year after inclusion.
CONCLUSIONS: This is the first multicentre trial with a cluster randomised trial design to investigate whether a structured alcohol cessation support program reduces recurrent acute pancreatitis in patients after a first episode of acute alcoholic pancreatitis, as compared with current practice.
BACKGROUND: Netherlands Trial Registry (NL8852). Prospectively registered.

暂无摘要。

Excessive alcohol intake is a major risk factor for pancreatitis, sensitizing the exocrine pancreas to stressors by mechanisms that remain obscure. Impaired autophagy drives nonalcoholic pancreatitis, but the effects of ethanol (EtOH) and alcoholic pancreatitis on autophagy are poorly understood. Here, we find that ethanol reduces autophagosome formation in pancreatic acinar cells, both in a mouse model of alcoholic pancreatitis induced by a combination of EtOH diet and cerulein (a CCK ortholog) and in EtOH+CCK-treated acinar cells (ex vivo model). Ethanol treatments decreased pancreatic level of LC3-II, a key mediator of autophagosome formation. This was caused by ethanol-induced upregulation of ATG4B, a cysteine protease that, cell dependently, regulates the balance between cytosolic LC3-I and membrane-bound LC3-II. We show that ATG4B negatively regulates LC3-II in acinar cells subjected to EtOH treatments. Ethanol raised ATG4B level by inhibiting its degradation, enhanced ATG4B enzymatic activity, and strengthened its interaction with LC3-II. We also found an increase in ATG4B and impaired autophagy in a dissimilar, nonsecretagogue model of alcoholic pancreatitis induced by EtOH plus palmitoleic acid. Adenoviral ATG4B overexpression in acinar cells greatly reduced LC3-II and inhibited autophagy. Furthermore, it aggravated trypsinogen activation and necrosis, mimicking key responses of ex vivo alcoholic pancreatitis. Conversely, shRNA Atg4B knockdown enhanced autophagosome formation and alleviated ethanol-induced acinar cell damage. The results reveal a novel mechanism, whereby ethanol inhibits autophagosome formation and thus sensitizes pancreatitis, and a key role of ATG4B in ethanol\'s effects on autophagy. Enhancing pancreatic autophagy, particularly by downregulating ATG4B, could be beneficial in mitigating the severity of alcoholic pancreatitis.NEW & NOTEWORTHY Ethanol sensitizes mice and humans to pancreatitis, but the underlying mechanisms remain obscure. Autophagy is important for maintaining pancreatic acinar cell homeostasis, and its impairment drives pancreatitis. This study reveals a novel mechanism, whereby ethanol inhibits autophagosome formation through upregulating ATG4B, a key cysteine protease. ATG4B upregulation inhibits autophagy in acinar cells and aggravates pathological responses of experimental alcoholic pancreatitis. Enhancing pancreatic autophagy, particularly by down-regulating ATG4B, could be beneficial for treatment of alcoholic pancreatitis.

OBJECTIVE: The study aims to determine and quantify the stratified risk of recurrent pancreatitis (RP) after the first episode of acute pancreatitis in relation to etiology and severity of disease.
METHODS: A systematic review and meta-analysis in compliance with PRISMA statement standards was conducted. A search of electronic information sources was conducted to identify all studies investigating the risk of RP after the first episode of acute pancreatitis. Proportion meta-analysis models using random effects were constructed to calculate the weighted summary risks of RP. Meta-regression was performed to evaluate the effect of different variables on the pooled outcomes.
RESULTS: Analysis of 57,815 patients from 42 studies showed that the risk of RP after first episode was 19.8% (95% confidence interval [CI] 17.5-22.1%). The risk of RP was 11.9% (10.2-13.5%) after gallstone pancreatitis, 28.7% (23.5-33.9%) after alcohol-induced pancreatitis, 30.3% (15.5-45.0%) after hyperlipidemia-induced pancreatitis, 38.1% (28.9-47.3%) after autoimmune pancreatitis, 15.1% (11.6-18.6%) after idiopathic pancreatitis, 22.0% (16.9-27.1%) after mild pancreatitis, 23.9% (12.9-34.8%) after moderate pancreatitis, 21.6% (14.6-28.7%) after severe pancreatitis, and 6.6% (4.1-9.2%) after cholecystectomy following gallstone pancreatitis. Meta-regression confirmed that the results were not affected by the year of study (P = 0.541), sample size (P = 0.064), length of follow-up (P = 0.348), and age of patients (P = 0.138) in the included studies.
CONCLUSIONS: The risk of RP after the first episode of acute pancreatitis seems to be affected by the etiology of pancreatitis but not the severity of disease. The risks seem to be higher in patients with autoimmune pancreatitis, hyperlipidemia-induced pancreatitis, and alcohol-induced pancreatitis and lower in patients with gallstone pancreatitis and idiopathic pancreatitis.