Pancreas最新文献

Background: Acute pancreatitis (AP) is a common cause of acute abdominal pain, and about 25% of AP patients will develop severe acute pancreatitis (SAP), causing damage to multiple organ functions and eventually death. Ferroptosis has recently been identified as significantly contributing to SAP progression. Our study aims to elucidate a novel mechanism of ferroptosis that which O-GlcNAcylation of ATF3 regulates in the context of SAP.

Methods: AR42J cells were treated with L-Arginine to induce SAP cell model. Levels of GSH, MDA, LPO, Fe2+, and LDH were measured by their commercial kits. The Fura-3 AM probes and C11 BODIPY 581/591 probe were used to detect Ca2+ levels or lipid ROS. To demonstrate the regulatory relationship between ATF3 and ACSL1, ChIP and dual-luciferase reporter assays were applied. Co-IP and sWGA pull-down assays were conducted to verify the O-GlcNAcylation level. The co-localization of OGT and ATF3 was displayed by immunofluorescence. Male SD rats were intraperitoneally injected with L-Arginine to establish a SAP model. Pancreatic histopathological alterations were subsequently evaluated by HE staining.

Results: Ferroptosis and ATF3 increased by treating L-Arginine in AR42J cells. ATF3 knockdown suppressed MDA, LPO, Fe2+, and lipid ROS levels but improved GSH and cell viability. OGT was elevated in SAP, and it promoted the O-GlcNAcylation of ATF3, resulting in the aggravation of ferroptosis. Both OGT inhibitor and OGT knockdown limited O-GlcNAcylation, ATF3, and ACSL1 levels. ATF3 directly bound to the promoter region of ACSL1 to upregulate its expression. ACSL1 overexpression abolished the suppression of ferroptosis in AR42J cells caused by ATF3 reduction. Inhibiting the ATF3 O-GlcNAcylation suppresses ferroptosis and attenuates pancreatic tissue injury in SAP rat.

Conclusion: The OGT-mediated O-GlcNAcylation of ATF3 is significantly enhanced, thereby promoting the transcriptional activity of ASCL1 and exacerbating ferroptosis in SAP.

Background: Standardized admission order entry systems (OES) and clinical decision support (CDS) tools can facilitate implementation of evidence-based practice. We conducted a mixed-methods analysis incorporating quantitative analysis of OES/CDS usage as well as qualitative analysis to identify barriers and facilitators related to usage of acute pancreatitis (AP)-specific OES-CDS.

Methods: Quantitative analysis: A retrospective cohort study of hospitalized encounters for AP (defined by diagnosis codes and lipase or amylase >3x normal) was conducted across 12 hospitals within an integrated health system from September 2014 through October 2022 to evaluate adoption of the AP OES/CDS, relationship to length-of-stay (LOS≥7 d), and in-hospital mortality adjusted for patient clinical and demographic characteristics. Qualitative analysis: Semi-structured interviews of focus groups identified themes related to perceived benefits, barriers, and improvements to the OES/CDS.

Results: Among 16,874 AP hospitalizations during the study, annual use of the AP OES/CDS peaked in 2021 at 7.4%. Use of AP OES/CDS was associated with reduction in prolonged LOS (OR: 0.81, 95% CI: 0.69-0.94). This finding was consistent after adjusting age, sex, race/ethnicity, and comorbidity indices. No significant difference in mortality was associated with OES usage (OR: 0.89, 95% CI: 0.61-1.32). Barriers to OES adoption included lack of awareness, competition with other tools, and complexity of patient case-mix.

Conclusion: Although adoption was limited, usage of an AP OES/CDS tool was associated with a decrease in prolonged length-of-stay. Future efforts to expand the reach of such instruments through provider awareness and refinement of the instrument may facilitate broader impact for management of patients with acute pancreatitis.

Background: Splanchnic Vein Thrombosis (SVT) is common in acute pancreatitis (AP) and often leads to intra-abdominal collaterals, increasing the risk of bleeding during interventions. However, data on its impact on intervention outcomes are limited. We prospectively assessed the effect of SVT on outcomes of interventions for symptomatic pancreatic fluid collections (PFCs).

Methods: Fifty patients (mean age: 40.9 y; 62% male) with symptomatic PFCs were prospectively evaluated. Contrast-enhanced CT was used to assess PFCs, detect SVT, and identify intra-abdominal venous collaterals (IAVCs). Patients underwent percutaneous drainage (PCD), endoscopic transmural drainage (TMD), or surgery, based on the treating clinician's discretion. Follow-up lasted six months, and outcomes were compared between patients with and without SVT.

Results: SVT was present in 18 (36%) patients; IAVCs were seen in 8 (16%). Splenic vein thrombosis occurred in 17 (34%), portal vein in 7 (14%), and superior mesenteric vein in 8 (16%). Thirty-nine (78%) underwent PCD, 11 (22%) TMD, and 13 (26%) required surgery. Eleven (22%) patients died, with similar mortality between the SVT and non-SVT groups. Hospital and ICU stay lengths were comparable. Bleeding rates did not differ significantly (SVT vs. no SVT: 2 [11.1%] vs. 2 [6.25%]; P=0.612).

Conclusions: SVT was not associated with increased complications, bleeding risk, or mortality following interventions for symptomatic PFCs in AP.

Objectives: Genetics is significant contributor to acute recurrent pancreatitis. This study evaluates the prevalence of genetic variants and assesses electrophysiological characteristics in Israeli patients.

Methods: Patients with ≥ two episodes of acute pancreatitis, no history of drug use, normal IgG4 levels, and normal cholangiopancreatographic findings were included. Genetic analysis targeted the PRSS1, SPINK1, CTRC, CFTR, CPA1 and TRPV6 genes, as well as the CEL-HYB1 allele. Sweat testing and nasal potential difference measurements were also performed.

Results: Seventy-nine patients (median age 13 years; range 2-61) were referred between 2015 and 2021. 45 (57.0%) carried at least one genetic variant; 18 patients carried 2 or more variants. CFTR variants were the most common (35.4%), followed by PRSS1 (11.4%), SPINK1 (10.1%), and CTRC (10.1%). The rare PRSS1 p.Lys23Arg variant was prevalent among Jewish Georgian patients (n=8). Patients with genetic variants were younger than those without ( P <0.0035). Of the 71 patients who underwent nasal potential difference testing, 2 (5.6%) had abnormal results. Sweat test in 66 patients showed a mean value of 36 ± 16 mmol/L, six had results above 60 mmol/L; two of these carried CFTR variants TG[11]T[5] and p.Leu997Phe but had normal nasal potential.

Conclusions: More than half of acute recurrent pancreatitis cases had a genetic basis, presenting at a younger age. CFTR variants were the most prevalent. The high prevalence of the PRSS1 p.Lys23Arg variant among Jewish Georgian individuals suggests a potential founder effect. These findings highlight the importance of genetic evaluation in the diagnosis and management of acute recurrent pancreatitis.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) serves as an essential procedure for diagnosing and treating pancreaticobiliary disorders, however it frequently results in post-ERCP pancreatitis (PEP), its most common complication. Identifying risk factors for PEP is crucial given its potential for significant morbidity and mortality.

Objective: To systematically review and evaluate existing PEP risk prediction models, thereby establishing an evidence-based framework to inform clinical decision-making and guide future model development.

Design: Systematic review and meta-analysis conducted in accordance with PRISMA 2020 guidelines.

Methods: We performed a comprehensive literature search across multiple databases (PubMed, Scopus, Embase, etc.) from their inception till February 2025. The inclusion criteria focused on studies that developed or validated predictive models for PEP in adult patients undergoing ERCP. Two reviewers independently extracted data and assessed methodological quality using the PROBAST tool.

Results: From 466 initially identified records, we analyzed 11 studies comprising 12 predictive models. The pooled area under the receiver operating characteristic curve (AUC) was 0.798 (95% confidence interval: 0.727-0.876). Key independent predictors of PEP included endoscopic sphincterotomy (EST), previous pancreatitis, age, operative time, and intubation difficulty. However, significant methodological heterogeneity and potential bias were evident across studies. Most models were developed using logistic regression, with only one study employing machine learning techniques. Notably, only three studies conducted external validation, underscoring substantial limitations in current predictive modeling approaches.

Conclusion: Existing PEP prediction models demonstrate overall good discrimination but are limited by methodological heterogeneity and scarce external validation. Clinically, validated models can support risk stratification to guide preventive strategies (e.g., rectal NSAIDs, aggressive hydration, selective prophylactic pancreatic stenting) alongside clinical judgment. Future research should prioritize multicenter prospective validation, robust calibration and decision-curve analyses, impact assessments, and explainable machine learning models integrated with electronic health record systems.

Background: Social determinants of health (SDH) encompass socioeconomic and environmental factors that influence individual health outcomes. While SDH has been studied in relation to cardiovascular and metabolic diseases, its potential relationship with acute pancreatitis (AP) remains insufficiently explored.

Methods: We conducted a prospective cohort study using data from the UK Biobank, including over 340,000 participants without a history of AP at baseline. A composite SDH score was constructed from multiple indicators and the association between SDH and incident AP was examined using Cox proportional hazards models. Restricted cubic spline (RCS) regression was used to assess dose-response relationships. Stratified analyses were performed by demographic and clinical subgroups. Associations between SDH and AP-related diseases were also investigated.

Results: Elevated SDH scores were significantly associated with increased AP risk (P<0.001), with a linear dose-response relationship confirmed by RCS analysis. After full adjustment, the risk of AP was found to be higher in participants with unfavorable SDH (HR 1.52, 95%CI 1.37-1.70) compared to those with favorable SDH. In post-AP individuals, participants in the higher SDH group had increased risks of chronic pancreatitis (CP) and type 2 diabetes mellitus (T2DM). However, no significant association was found between SDH and post-AP pancreatic cancer (PC) (P=0.632).

Conclusions: Social disadvantage, as reflected by higher SDH scores, is associated with high risk of AP and AP-related diseases. These findings underscore the importance of considering social context in clinical and public health efforts to reduce the burden of pancreatic diseases.