Study on the Prediction of Liver Injury in Acute Pancreatitis Patients by Radiomic Model Based on Contrast-Enhanced Computed Tomography.

OBJECTIVES: to predict liver injury in acute pancreatitis (AP) patients by establishing a radiomics model based on contrast-enhanced computed tomography (CECT). METHODS: a total of 1223 radiomic features were extracted from late arterial-phase pancreatic CECT images of 209 AP patients (146 in the training cohort and 63 in the test cohort), and the optimal radiomic features retained after dimensionality reduction by least absolute shrinkage and selection operator (LASSO) were used to construct a radiomic model through logistic regression analysis. In addition, clinical features were collected to develop a clinical model, and a joint model was established by combining the best radiomic features and clinical features to evaluate the practicality and application value of the radiomic models, clinical model and combined model. RESULTS: four potential features were selected from the pancreatic parenchyma to construct the radiomic model, and the area under the receiver operating characteristic curve (AUC) of the radiomic model was significantly greater than that of the clinical model for both the training cohort (0.993 vs. 0.653, p = 0.000) and test cohort (0.910 vs. 0.574, p = 0.000). The joint model had a greater AUC than the radiomics model for both the training cohort (0.997 vs. 0.993, p = 0.357) and test cohort (0.925 vs. 0.910, p = 0.302). CONCLUSIONS: the radiomic model based on CECT has good performance in predicting liver injury in AP patients and can guide clinical decision-making and improve the prognosis of patients with AP.

Acute Pancreatitis With Normal Amylase and Lipase: A Diagnostic Dilemma.

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.

Poorly Controlled New-Onset Diabetes Mellitus and Other Atypical Signs as an Early Sign of Pancreatic Adenocarcinoma.

A 50-year-old man presented with poorly controlled new-onset diabetes mellitus. Six months after diagnosis, episodes of intense abdominal pain with vomiting appeared. Abdominal CT revealed signs of acute pancreatitis with structural changes in the pseudocysts. In the absence of biliary lithiasis or a toxic etiology of acute pancreatitis, the patient progressed unfavorably with increased abdominal pain and fever. Control imaging tests (two and 10 months later) showed the evolution of phlegmonous/necrotic collections, together with portal vein thrombosis and splenomegaly. Given the suggestive signs of possible occult malignancy, such as portal thrombosis, histological analysis of the ascitic fluid revealed a pancreatic adenocarcinoma. Despite the initiation of chemotherapy, the patient died 12 months after diagnosis.

Acute pancreatitis and refractory hypercalcemia in the third trimester caused by parathyroid carcinoma.

BACKGROUND: Hypercalcemia can be a rare contributor to acute pancreatitis (AP) in pregnancy. This is primarily due to primary hyperparathyroidism (PHPT), resulting from parathyroid carcinoma. We exhibited a case report to analyze the diagnosis and treatment during the onset of hypercalcemia-induced AP. CASE PRESENTATION: A 32-year-old primigravida presented with acute pancreatitis near full-term gestation. Following a cesarean delivery, there was a reduction in serum amylase and peripancreatic exudate, but her serum calcium concentrations persistently elevated over 4.0 mmol/L. Interventions to lower the hypercalcemia were only temporarily effective, until a high serum parathyroid hormone (PTH) concentration of 1404 pg/mL was detected. Ultrasound revealed a 31 mm × 24 mm hypoechoic oval nodule in the left lower lobe of the thyroid gland. She underwent a parathyroidectomy, resulting in a dramatic decrease in serum PTH level, from preoperative levels of 2051 pg/mL to 299 pg/mL just 20 minutes after removal. Similarly, her serum calcium declined from 3.82 mmol/L to 1.73 mmol/L within 24 hours postoperatively. The final histopathology suggested parathyroid carcinoma. CONCLUSION: When refractory hypercalcemia is present, serum PTH levels should be measured to determine PHPT. Parathyroidectomy is the optimal strategy for alleviating hypercalcemia and clarifying the underlying pathology.

Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress.

Background: Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats. Methods: Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250 mg/100 g, intraperitoneal), and sitagliptin + L-arginine-treated group (10 mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1 hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals. Results: L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/ß, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP. Conclusion: Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.

Intra-articular Steroid Injection as the Etiology of Acute Pancreatitis.

Acute interstitial pancreatitis is typically caused by gallstones and alcohol use. Less common causes include infection and drugs. Patients present with epigastric pain and often require pain medications and hospitalization depending on severity. We present a unique case of drug-induced pancreatitis likely caused by intra-articular corticosteroid injections on two separate occasions in the same patient. In both instances, other etiologies were ruled out. Given the temporal relationship between the intra-articular corticosteroid injection and presentation of pancreatitis, the corticosteroid injection was the likely etiology. This case suggests that intra-articular steroids should be included as an etiology of drug-induced pancreatitis.

Involvement of circ_0029407 in Caerulein-Evoked Cytotoxicity in Human Pancreatic Cells via the miR-579-3p/TLR4/NF-κB Pathway.

Acute pancreatitis (AP) is the most prevalent gastrointestinal inflammatory disease. Circular RNAs (circRNAs) are implicated in the development of AP. Here, we identified the precise action of circ_0029407 in AP development. Human pancreatic epithelial cells (HPECs) were stimulated with caerulein. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays, respectively. Circ_0029407, microRNA (miR)-579-3p, and toll-like receptor 4 (TLR4) were quantified by a qRT-PCR or western blot assay. Dual-luciferase reporter and RNA pull-down assays were performed to evaluate the direct relationship between miR-579-3p and circ_0029407 or TLR4. Our results indicated that circ_0029407 was markedly overexpressed in AP serum samples and caerulein-stimulated HPECs. Reduction of circ_0029407 attenuated caerulein-imposed HPEC damage by promoting cell proliferation and repressing cell apoptosis and inflammation. Mechanistically, circ_0029407 contained a miR-579-3p binding site, and miR-579-3p downregulation reversed the effect of circ_0029407 reduction on caerulein-imposed HPEC damage. TLR4 was identified as a direct and functional target of miR-579-3p, and TLR4 overexpression reversed the impact of miR-579-3p upregulation on attenuating caerulein-imposed HPEC damage. Moreover, circ_0029407 regulated the TLR4/nuclear factor NF-kappaB (NF-κB) signaling by acting as a competing endogenous RNA (ceRNA) for miR-579-3p. Our study suggests that circ_0029407 regulates caerulein-imposed cell injury in human pancreatic cells at least in part via the TLR4/NF-κB signaling pathway by functioning as a ceRNA for miR-579-3p.

Revealing Prdx4 as a potential diagnostic and therapeutic target for acute pancreatitis based on machine learning analysis.

Acute pancreatitis (AP) is a common systemic inflammatory disease resulting from the activation of trypsinogen by various incentives in ICU. The annual incidence rate is approximately 30 out of 100,000. Some patients may progress to severe acute pancreatitis, with a mortality rate of up to 40%. Therefore, the goal of this article is to explore the key genes for effective diagnosis and treatment of AP. The analysis data for this study were merged from two GEO datasets. 1357 DEGs were used for functional enrichment and cMAP analysis, aiming to reveal the pathogenic genes and potential mechanisms of AP, as well as potential drugs for treating AP. Importantly, the study used LASSO and SVM-RFE machine learning to screen the most likely AP occurrence biomarker for Prdx4 among numerous candidate genes. A receiver operating characteristic of Prdx4 was used to estimate the incidence of AP. The ssGSEA algorithm was employed to investigate immune cell infiltration in AP. The biomarker Prdx4 gene exhibited significant associations with a majority of immune cells and was identified as being expressed in NKT cells, macrophages, granulocytes, and B cells based on single-cell transcriptome data. Finally, we found an increase in Prdx4 expression in the pancreatic tissue of AP mice through immunohistochemistry. After treatment with recombinant Prdx4, the pathological damage to the pancreatic tissue of AP mice was relieved. In conclusion, our study identified Prdx4 as a potential AP hub gene, providing a new target for treatment.

Interleukin-22 Alleviates Caerulein-Induced Acute Pancreatitis by Activating AKT/mTOR Pathway.

BACKGROUND: Acute pancreatitis (AP) is one of the most common acute abdominal disorders; due to the lack of specific treatment, the treatment of acute pancreatitis, especially serious acute pancreatitis (SAP), is difficult and challenging. We will observe the changes of Interleukin -22 levels in acute pancreatitis animal models, and explore the mechanism of Interleukin -22 in acute pancreatitis. OBJECTIVE: This study aims to assess the potential protective effect of Interleukin -22 on caerulein-induced acute pancreatitis and to explore its mechanism. METHODS: Blood levels of amylase and lipase and Interleukin -22 were assessed in mice with acute pancreatitis. In animal model and cell model of caerulein-induced acute pancreatitis, the mRNA levels of P62 and Beclin-1 were determined using PCR, and the protein expression of P62, LC3-II, mTOR, AKT, p-mTOR, and p-AKT were evaluated through Western blot analysis. RESULTS: Interleukin -22 administration reduced blood amylase and lipase levels and mitigated tissue damage in acute pancreatitis mice model. Interleukin -22 inhibited the relative mRNA levels of P62 and Beclin-1, and the Interleukin -22 group showed a decreased protein expression of LC3-II and P62 and the phosphorylation of the AKT/mTOR pathway. Furthermore, we obtained similar results in the cell model of acute pancreatitis. CONCLUSION: This study suggests that Interleukin -22 administration could alleviate pancreatic damage in caerulein-induced acute pancreatitis. This effect may result from the activation of the AKT/mTOR pathway, leading to the inhibition of autophagy. Consequently, Interleukin -22 shows potential as a treatment.

A radiomics model of contrast-enhanced computed tomography for predicting post-acute pancreatitis diabetes mellitus.

Background: Diabetes mellitus can occur after acute pancreatitis (AP), but the accurate quantitative methods to predict post-acute pancreatitis diabetes mellitus (PPDM-A) are lacking. This retrospective study aimed to establish a radiomics model based on contrast-enhanced computed tomography (CECT) for predicting PPDM-A. Methods: A total of 374 patients with first-episode AP were retrospectively enrolled from two tertiary referral centers. There were 224 patients in the training cohort, 56 in the internal validation cohort, and 94 in the external validation cohort, and there were 86, 22, and 27 patients with PPDM-A in these cohorts, respectively. The clinical characteristics were collected from the hospital information system. A total of 2,398 radiomics features, including shape-based features, first-order histogram features, high order textural features, and transformed features, were extracted from the arterial- and venous-phase CECT images. Intraclass correlation coefficients were used to assess the intraobserver reliability and interobserver agreement. Random forest-based recursive feature elimination, collinearity analysis, and least absolute shrinkage and selection operator (LASSO) were used for selecting the final features. Three classification methods [eXtreme Gradient Boosting (XGBoost), Adaptive Boosting, and Decision Tree] were used to build three models and performances of the three models were compared. Each of the three classification methods were used to establish the clinical model, radiomics model, and combined model for predicting PPDM-A, resulting in a total of nine classifiers. The predictive performances of the models were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. Results: Eleven radiomics features were selected after a reproducibility test and dimensionality reduction. Among the three classification methods, the XGBoost classifier showed better and more consistent performances. The AUC of the XGBoost's radiomics model to predict PPDM-A in the training, internal, and external cohorts was good (0.964, 0.901, and 0.857, respectively). The AUC of the XGBoost's combined model to predict PPDM-A in the training, internal, and external cohorts was good (0.980, 0.901, and 0.882, respectively). The AUC of the XGBoost's clinical model to predict PPDM-A in the training, internal, and external cohorts did not perform well (0.685, 0.733, and 0.619, respectively). In the external validation cohort, the AUC of the XGBoost's radiomics model was significantly higher than that of the clinical model (0.857 vs. 0.619, P<0.001), but there was no significant difference between the combined and radiomics models (0.882 vs. 0.857, P=0.317). Conclusions: The radiomics model based on CECT performs well and can be used as an early quantitative method to predict the occurrence of PPDM-A.

The outcomes of COVID-19 and acute pancreatitis: a systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) was first reported in China at the end of 2019. Several case studies have documented a probable association between infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and acute pancreatitis (AP). The objective of this study was to provide a complete analysis of existing literature that compares the clinical outcomes of AP in patients with COVID-19 and those without COVID-19. The intention was to further our understanding of the involvement of SARS-CoV-2 in the development of pancreatitis. Methods: Between January 2019 and December 2022, we searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus. Nine studies (3,160 patients) were included. In this meta-analysis, Stata 12.0. was utilized. The information provided in this study is presented following the MOOSE reporting checklist. Results: Mortality [odds ratio (OR) =3.95, 95% confidence interval (CI): 2.87, 5.43, P<0.001], intensive care unit (ICU) administration (OR =3.74, 95% CI: 2.26, 6.20, P<0.001), mechanical ventilation (OR =4.84, 95% CI: 2.14, 10.96, P<0.001), severe pancreatitis (OR =2.71, 95% CI: 1.04, 7.04, P=0.042), etiology of idiopathic and unknown (OR =4.75, 95% CI: 1.80, 12.56, P=0.002), necrotizing pancreatitis (OR =1.88, 95% CI: 1.28, 2.76, P=0.001), and length of hospital stay [weighted mean difference (WMD) =5.10, 95% CI: 2.79, 7.41, P<0.001] were more significantly increased in AP cases with COVID-19 than those without it. Conclusions: In conclusion, the findings of this study indicate a potential worsening of AP outcomes in patients affected by COVID-19.

Gastrodin ameliorates acute pancreatitis by modulating macrophage inflammation cascade via inhibition the p38/NF-κB pathway.

Acute pancreatitis (AP) is a prevalent, destructive, non-infectious pancreatic inflammatory disease, which is usually accompanied with systemic manifestations and poor prognosis. Gastrodin (4-hydroxybenzyl alcohol 4-O-ß-d-glucopyranoside) has ideal anti-inflammatory effects in various inflammatory diseases. However, its potential effects on AP had not been studied. In this study, serum biochemistry, H&E staining, immunohistochemistry, immunofluorescence, western blot, real-time quantitative PCR (RT-qPCR) were performed to investigate the effects of Gastrodin on caerulein-induced AP pancreatic acinar injury model in vivo and lipopolysaccharide (LPS) induced M1 phenotype macrophage model in vitro. Our results showed that Gastrodin treatment could significantly reduce the levels of serum amylase and serum lipase while improving pancreatic pathological morphology. Additionally, it decreased secretion of inflammatory cytokines and chemokines, and inhibited the levels of p-p38/p38, p-IκB/IκB as well as p-NF-κB p-p65/NF-κB p65. Overall our findings suggested that Gastrodin might be a promising therapeutic option for patients with AP by attenuating inflammation through inhibition of the p38/NF-κB pathway mediated macrophage cascade.

The effect of ferroptosis on pancreatic inflammatory injury in acute pancreatitis / 西安交通大学学报(医学版)

【Objective】 To observe the presence of ferroptosis in acute pancreatitis (AP) and the effect of iron ions on the NLRP3 pathway so as to explore the possible mechanisms for the protection of pancreatic alveolar cells. 【Methods】 A total of 45 male C57BL/6 mice were randomly divided into three groups (control, AP, and AP+2′2-bipyridyl). A total of 12 injections (caerulein, 50 μg/kg) were given at one-hour intervals. The AP+2′2-bipyridyl group was pretreated with 2′2-bipyridyl (20 mg/kg) for 1 hour, and then injected with caerulein. The control group was injected with an equal volume of normal saline. All of the mice were killed one hour after the last injection. Their pancreases were harvested for histopathological evaluation, immunohistochemistry analyses, and Western blotting. 【Results】 The ferroptosis inhibitor 2′2-bipyridyl could prevent the accumulation of iron ions, reduce the formation of lipid peroxides and the injury in the process of AP, and it also reduced pancreatic inflammation through NLRP3 pathway. 【Conclusion】 This experiment confirmed the real existence of ferroptosis, a form of cell death, in AP, and revealed that inhibition of ferroptosis can reduce pancreatic inflammatory damage in AP.

Risk factors for acute pancreatitis in long-term drinking participants: a longitudinal UK Biobank-based study / 西安交通大学学报(医学版)

【Objective】 To examine risk factors for acute pancreatitis (AP) in individuals with chronic alcohol consumption habits. 【Methods】 The study incorporated participants from the initial survey (2006-2010) and subsequent follow-ups (2014+) taken from the UK Biobank database, with the observation period ending on November 30, 2022. During this period, 176 individuals were newly diagnosed with AP, while 59,512 remained unaffected. Vital characteristics of the target population, such as their medical histories, surgical experiences and dietary patterns, were collected during the enrolment phase (2006-2010). The Cox proportional hazard model was employed to ascertain whether these characteristics were potent risk factors for AP. Concurrently, a subgroup from the target population with documented drinking behavior was selected. The multivariate Cox proportional hazard model was utilized to analyze the relationship of the established factors, variances in alcohol consumption, and increased alcohol intake (Δ) with the onset of AP, and whether the additional alcohol intake served as a risk factor. 【Results】 Multivariate analysis revealed that consumption quantity of cooked vegetables inversely correlated with AP risk (HR=0.44, 0.39, 0.42 and 0.41 for one, two, three and four+ tablespoons per day, respectively, as compared to non-consumers). Coffee consumption (2-3 cups per day) also reduced AP risk (HR=0.45 for 2 cups/day; HR=0.39 for 3 cups/day as compared to non-coffee drinkers). However, those with biliary disease without cholecystectomy exhibited a marked increase in AP risk (HR=7.82), which reduced albeit remained elevated for those with biliary disease post-cholecystectomy (HR=2.15). Subgroup analysis showed minimal impact of alcohol intake levels on AP incidence. Yet, increased alcohol consumption (Δ of 1 bottle/week) was linked to a heightened AP risk (HR=1.05, 95% CI:1.02-1.09, P<0.05). 【Conclusion】 Among longstanding alcohol consumers, a diet rich in cooked vegetables and moderate coffee consumption offers protective effects against AP. Conversely, biliary disease (particularly without cholecystectomy) and elevated alcohol intake present considerable risk factors for the development of this condition.

Clinical characteristics of fungal infection in patients with infected pancreatic necrosis / 西安交通大学学报(医学版)

【Objective】 To analyze the clinical features of patients with infected pancreatic necrosis (IPN) complicated with fungal infection so as to identify possible risk factors for death. 【Methods】 We analyzed the clinical data of patients with IPN admitted to Xuanwu Hospital Capital Medical University from January 1, 2017 to December 31, 2021. According to the results of pancreatic necrotic tissue and drainage fluid culture, the patients were divided into the group with fungal infection and the group without fungal infection. The baseline data, clinical features and outcomes of the two groups were compared, and the risk factors for death in patients with fungal infection were analyzed. 【Results】 We included a total of 214 patients in the study, of whom 49 patients in the fungal infection group had wider necrotic involvement, lower hematopoietic volume, and higher blood glucose at admission. Patients with fungal infection had a higher proportion of multidrug-resistant bacteria (MDRB), and hospital and ICU stay as well as parenteral nutrition duration were also longer. In the group of patients with fungal infection, the proportion of patients undergoing surgery did not increase (P>0.05), but the proportion of patients with perioperative organ failure and death was higher (P<0.05). Candida albicans (44.8%) was the most common fungus detected, followed by Candida parapsilosis (28.6%) and Candida tropicalis (8.2%). Logistic regression analysis showed that MDRB infection (OR=1.37, 95% CI:1.02-1.83), fungemia (OR=1.53, 95% CI:1.06-2.23), hyperglycemia (OR=1.65, 95% CI:1.28-2.10), new organ failure (OR=1.65, 95% CI:1.19-2.29) and bleeding complications (OR=1.64, 95% CI:1.28-2.10) after surgery were risk factors for death in patients with fungal infection. 【Conclusion】 Fungal infection increases mortality in patients with IPN and the incidence of new organ failure after surgery. Attention to fungemia, MDRB infection, hyperglycemia, organ failure and postoperative bleeding can help reduce the risk of death.

Acute pancreatitis in intraductal papillary mucinous neoplasm: a single-center retrospective cohort study with systematic review and meta-analysis.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN. METHODS: In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model. RESULTS: The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN. CONCLUSIONS: AP is predictive of malignancy in patients with IPMN.

Therapeutic role of interleukin-1 receptor antagonist in pancreatic diseases: mendelian randomization study.

Background: The interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor antagonist (IL-1RA) levels reduce the risk of acute and chronic pancreatitis and pancreatic cancer. Methods: Genetic variants associated with blood IL-1RA levels at the genome-wide significance level and located 5MB downstream or upstream of the IL1RN gene were extracted from a genome-wide meta-analysis of 21,758 participants. After pruning, genetic variants without linkage disequilibrium were used as genetic instrument for IL-1RA. Summary-level data on acute and chronic pancreatitis and pancreatic cancer were obtained from the UK Biobank and FinnGen studies. The associations were meta-analyzed for one outcome from two sources. Results: Genetically predicted higher levels of IL-1RA were associated with a lower risk of acute and chronic pancreatitis and pancreatic cancer. In the meta-analysis of UK Biobank and FinnGen, the combined odds ratio was 0.87 (95% confidence interval [CI] 0.77-0.97, P=0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82, P=2.93×10-8) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96, P=0.009) for pancreatic cancer per one standard deviation increment in genetically predicted levels of IL-1RA. Conclusion: This study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.

Genotype 4 HEV infection triggers the initiation and development of acute pancreatitis.

The role of HEV infection in AP remains unclear. 1000 patients with AP and 1000 HCs were enrolled, and pancreatitis was evaluated in HEV-infected rhesus macaques. The positive rates of anti-HEV IgG, IgM, and HEV RNA in the AP patients were significantly higher than HCs. With the increase in the severity of AP, the percentage of HEV infection increased. AP patients were divided into AP- and AP + AHE groups. The percentage of severe AP in the AP + AHE group was significantly higher than in the AP- group. HEV infection was one of the main independent risk factors and had high predictive power for AP outcomes. A high level of HEV titer would prolong the recovery time and increase the risk of recurrent AP. Moreover, AP + AHE patients receiving conservative treatment showed a better prognosis. Furthermore, HEV can replicate in the pancreas of rhesus macaques. The pancreatic islet structure was damaged, the tissue was loose after 272 dpi, and a large amount of hyperemia appeared after 770 dpi. HEV infection also caused a large number of inflammatory cells in the pancreas. The pancreas and liver had a comparable viral load. HEV infection affects AP's occurrence, development, and prognosis.

CT characteristics of recurrent acute pancreatitis and acute pancreatitis in different stages-a retrospective cross-sectional study.

Background: Acute pancreatitis (AP), recurrent acute pancreatitis (RAP), and chronic pancreatitis (CP) are a continuum of the same disease. The course of RAP and AP is a dynamic process. Previous studies are contradictory regarding the severity of RAP and AP. We conducted this study to investigate the computed tomography (CT) characteristics of RAP and AP in the early and late stages; respectively. Methods: Patients who underwent contrast-enhanced computed tomography for symptoms during RAP or AP episodes were retrospectively collected from three tertiary hospitals in Sichuan Province, China from January 2015 to December 2019. The patients were categorized into RAP and AP groups based on recurrence and initial events. Both the RAP and AP groups were divided into early (first week) and late stages (after the first week) based on the 2012 revised Atlanta classification (RAC). Patient demographic data, RAC, CT findings, CT severity index (CTSI) scores, and extrapancreatic inflammation on CT scores in the early and late phases were analyzed between the two groups. The Wilcoxon signed-rank test, χ2 test, and Fisher's exact test were used to compare continuous and categorical variables between the two groups respectively. Results: In 683 RAP and 1,829 AP patients, the most common etiologies were hypertriglyceridemia and cholelithiasis, respectively. The RAP group had lower extrapancreatic inflammation on CT scores and Acute Physiology and Chronic Health Evaluation II scores than the AP group in the early stage (both P<0.001). The RAP group had higher CTSI scores than the AP group in the late stage (P=0.022). Conclusions: Compared with AP patients, the most common cause of RAP patients was hypertriglyceridemia in China, and the severity of RAP was lower than that of initial AP in the early stage and higher than that of initial AP in the late stage.

First Reported Case of Dulaglutide-Induced Acute Pancreatitis With Normal Serum Lipase Level.

Dulaglutide is being extensively used for non-insulin-dependent diabetes mellitus and congestive heart failure and is also being used as an off-label weight loss aid. Due to its wide use, we had to shed some light on this rare finding of normal lipase level in a patient with signs and symptoms suggestive of acute pancreatitis. A high index of clinical suspicion for acute pancreatitis despite normal lipase should warrant a low threshold for radiological imaging to rule it out.