Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

Elevated serum ferritin levels are associated with severity and prognosis of severe acute pancreatitis: a preliminary cohort study.

BACKGROUND: Serum ferritin (SF), as an acute-phase response protein, is used to reflect the degree of oxidative stress and systemic inflammatory responses. This study was designed to assess the effect of elevated SF levels on the severity of acute pancreatitis (AP). METHODS: From January 2013 to December 2020, 200 consecutive patients with AP were retrospectively reviewed to analyze the relationships among the etiologies of pancreatitis, the severity of the disease and SF levels. The receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess whether elevated SF levels could predict the onset of organ failure in AP. RESULTS: 92 (46%) had high SF levels (> 275 ng/ml). SF levels were not associated with the etiology of AP disease. Among patients with high SF levels, there was a significant increase in the proportion of patients with severe AP (23.1% vs. 76.9%) and a higher proportion of systemic inflammatory response scores (25.9% vs. 44.6%) in comparison to patients with normal SF levels. The area under the ROC curve for SF in predicting persistent organ failure was 0.812 [95% confidence interval 0.721-0.904]. CONCLUSIONS: F concentrations were positively correlated with the severity of AP, and quantitative assessment of SF can predict disease severity and organ failure in patients with AP.

Isoliquiritigenin ameliorates caerulein-induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages.

Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone-type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein-induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF-κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP.

Identification of a novel and heterozygous LMF1 nonsense mutation in an acute pancreatitis patient with severe hypertriglyceridemia, severe obesity and heavy smoking.

BACKGROUND: Hypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG. METHODS: A Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes. RESULTS: The patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene. CONCLUSIONS: This is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.

Prevalence and clinical characteristics of fatty pancreas in Yangzhou, China: A cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the prevalence and risk factors of fatty pancreas in Yangzhou, China. METHODS: This was a cross-sectional study. Initially, 2093 subjects were included in the study. After the exclusion of 865 subjects based on incomplete information, a total of 1228 subjects were selected for further analysis. The subjects were stratified into two groups (the fatty pancreas group and the non-fatty pancreas group) based on the results. Anthropometric and biochemical findings were compared between the groups. RESULTS: Among the 2093 study subjects, 56 (2.7%) had fatty pancreas. Overall, 53 out of 1228 subjects were diagnosed with fatty pancreas and included into the fatty pancreas group. Univariate analysis showed significant differences in age and the prevalence of general obesity, central obesity, alcohol consumption, metabolic syndrome and fatty liver between the two groups (all p < 0.01). The fatty pancreas group had higher levels of aspartate aminotransferase, alanine aminotransferase, serum uric acid, fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein, and lower levels of high-density lipoprotein than did the non-fatty pancreas group (all p < 0.05). Multivariate logistic regression analysis showed that age (p = 0.007), central obesity (p = 0.002) and fatty liver (p = 0.006) were independent risk factors for fatty pancreas, with odds ratios (ORs) of 1.034 (95% confidence interval (CI): 1.009-1.059), 5.364 (95% CI: 1.890-15.227), and 2.666 (95% CI: 1.332-5.338), respectively. CONCLUSION: The prevalence of fatty pancreas in the examined population is approximately 2.7%. Increased age, central obesity and fatty liver disease are independent risk factors for fatty pancreas.

A high level of integrin α6 expression in human intrahepatic cholangiocarcinoma cells is associated with a migratory and invasive phenotype.

BACKGROUND: The integrin α6 subunit is part of the integrin α6ß1 and α6ß4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed. METHODS: Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated. RESULTS: The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p < 0.05). The postoperative 5-year overall survival (OS) rate in patients with integrin α6(low) was higher than that of the integrin α6(high) group. CONCLUSIONS: Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC.

Pancreatitis and Pancreatic Cancer Risk.

Purpose: The present retrospective study aimed to explore the relationship between pancreatitis and pancreatic cancer in the population cohort of the UK Biobank (UKB) (https://www.ukbiobank.ac.uk). Methods: From the 500 thousand population cohort of UKB, according to the age and gender of patients with pancreatic cancer 1:10, matching the control without pancreatic cancer, the binary Logistic regression model was used to analyze the relationship between pancreatitis and pancreatic cancer, and subgroup analyses were used to identify potential effect modifiers. Results: A total of 1538 patients with pancreatic cancer were compared with 15 380 controls. In the fully adjusted model, patients with pancreatitis had a significantly increased risk of pancreatic cancer compared with no pancreatitis. The risk of pancreatitis and pancreatic cancer increased with the age of pancreatitis, and the risk of pancreatic cancer was highest in the 61 to 70 age group. In addition, in the first 3 years of acute pancreatitis, the risk of pancreatic cancer increased significantly with the increase in the duration of the disease (odds ratio [OR] 29.13, 95% confidence interval [CI]: 16.34-51.93), after 3 years, the trend of increase decreased. After more than 10 years, there was no significant correlation between the risk of acute pancreatitis and pancreatic cancer. However, patients with chronic pancreatitis were significantly associated with an increased risk of pancreatic cancer only in the first 3 years (OR 28.14, 95% CI: 14.86-53.31). Conclusion: Pancreatitis may associate with an increased risk of pancreatic cancer. The older the age of pancreatitis, the higher the risk of pancreatic cancer. The risk of pancreatic cancer increases significantly in the first 3 years of the course of pancreatitis. This may provide an alternative strategy for the early identification of individuals at high risk of pancreatic cancer.

Corrigendum: Prevalence and outcomes of pancreatic enzymes elevation in patients with COVID-19: a meta-analysis and systematic review.

[This corrects the article DOI: 10.3389/fpubh.2022.865855.].

Irisin inhibits neutrophil extracellular traps formation and protects against acute pancreatitis in mice.

INTRODUCTION: Irisin is a newly discovered myokine which links exercise to inflammation and inflammation-related diseases through macrophage regulation. However, the effect of irisin on the activity of inflammation related immune cells (such as neutrophils) has not been clearly described. OBJECTIVES: The objective of our study was to explore the effect of irisin on the neutrophil extracellular traps (NETs) formation. METHODS: Phorbol-12-myristate-13-acetate (PMA) was used to construct a classic neutrophil inflammation model that was used to observe the formation of NETs in vitro. We studied the effect of irisin on NETs formation and its regulation mechanism. Subsequently, acute pancreatitis (AP) was used to verify the protective effect of irisin in vivo, which was an acute aseptic inflammatory response disease model closely related to NETs. RESULTS: Our study found that addition of irisin significantly reduced the formation of NETs via regulation of the P38/MAPK pathway through integrin αVß5, which might be the one of key pathways in NETs formation, and which could theoretically offset the immunoregulatory effect of irisin. Systemic treatment with irisin reduced the severity of tissue damage common in the disease and inhibited the formation of NETs in pancreatic necrotic tissue of two classical AP mouse models. CONCLUSION: The findings confirmed for the first time that irisin could inhibit NETs formation and protect mice from pancreatic injury, which further elucidated the protective effect of exercise on acute inflammatory injury.

Adherence to pancreatic enzyme replacement therapy among patients with chronic pancreatitis in East China: a mixed methods study.

Pancreatic enzyme replacement therapy (PERT) has been recommended as the preferred method for pancreatic exocrine insufficiency caused by chronic pancreatitis (CP). However, at present, the patient-related factors for the poor PERT management are not clear, and there are no studies on the adherence to PERT in patients with CP in East China. This was a mixed-method study following the principle of sequential explanatory design and included two parts: a quantitative and qualitative study. A cross-sectional survey of medication adherence (MA) was first carried out, followed by a semi-structured interview to further explore and explain the influencing factors of adherence to PERT. Of the 148 patients included in this study, 48.0% had poor MA and only 12.8% had good MA. Multivariate logistic regression showed that lower levels of education and income were contributing factors for non-adherence to PERT. Semi-structured interviews with 24 patients revealed that the reasons for non-adherence also included lack of knowledge, self-adjustment of PERT, lifetime of medication, side effects of PERT, forgetfulness, financial burdens, and accessibility issues. The adherence to PERT was poor among patients with CP in East China. Healthcare providers should personalize medication strategies to improve patients' MA.

Elevated serum HbA1c level, rather than previous history of diabetes, predicts the disease severity and clinical outcomes of acute pancreatitis.

INTRODUCTION: The aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP). RESEARCH DESIGN AND METHODS: Patients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC). RESULTS: We included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group. CONCLUSIONS: Generally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP.

Prevalence and Outcomes of Pancreatic Enzymes Elevation in Patients With COVID-19: A Meta-Analysis and Systematic Review.

Background: Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients. Methods: A comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021. Results: A total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%-31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7-3.6), the pooled OR of ICU admission was 4.4 (2.8-6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6-7.4), 2.0 (0.5-8.7), and 2.3 (1.4-3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1-9.4), it seemed that mild elevation of PE to 1-3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5-3.5). Conclusions: PE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=295630, identifier: CRD42021295630.

Prediction of the severity of acute pancreatitis using machine learning models.

BACKGROUND: Acute pancreatitis (AP) is the most common pancreatic disease. Predicting the severity of AP is critical for making preventive decisions. However, the performance of existing scoring systems in predicting AP severity was not satisfactory. The purpose of this study was to develop predictive models for the severity of AP using machine learning (ML) algorithms and explore the important predictors that affected the prediction results. METHODS: The data of 441 patients in the Department of Gastroenterology in our hospital were analyzed retrospectively. The demographic data, blood routine and blood biochemical indexes, and the CTSI score were collected to develop five different ML predictive models to predict the severity of AP. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC). The important predictors were determined by ranking the feature importance of the predictive factors. RESULTS: Compared to other ML models, the extreme gradient boosting model (XGBoost) showed better performance in predicting severe AP, with an AUC of 0.906, an accuracy of 0.902, a sensitivity of 0.700, a specificity of 0.961, and a F1 score of 0.764. Further analysis showed that the CTSI score, ALB, LDH, and NEUT were the important predictors of the severity of AP. CONCLUSION: The results showed that the XGBoost algorithm can accurately predict the severity of AP, which can provide an assistance for the clinicians to identify severe AP at an early stage.

Baseline Serum Estradiol Level Is Associated with Acute Kidney Injury in Patients with Moderately Severe and Severe Acute Pancreatitis.

Background: Sexual dimorphism with critical diseases has been documented. However, the role of serum sex hormones for the presence of acute kidney injury (AKI) in moderately or severe acute pancreatitis (MSAP and SAP) patients remains controversial. Here we set out to evaluate whether early (first 48 h) serum estradiol level is associated with AKI in patients with MSAP and SAP. Patients and Methods. We retrospectively collected data from patients with preliminary diagnosis of MSAP and SAP from the Affiliated Hospital of Yangzhou University between January 2014 and June 2018. Serum sex hormones were extracted for further assessment within first 48 h following admission. Logistic regression analysis and the receiving operating characteristic (ROC) curve were applied to evaluate the association and correlation between serum sex hormones and AKI. Results: Data from a total of 122 patients with MSAP or SAP were enrolled in this study. There were no differences in the incidence of AKI between males and females. However, comparing with patients without AKI, those with AKI saw higher estradiol level (p ≤ 0.01) and slight higher progesterone level (p = 0.014) but similar testosterone level (p = 0.668). Interestingly, during both the manual selection and the stepwise backward logistic regression analysis, serum estradiol level was independently associated with AKI in patients with MSAP and SAP (OR 4.699, CI 1.783-12.386, and p = 0.002). Additionally, area under the curve of ROC (AUCROC) showed that serum estradiol level was a proper predictor for AKI (area under the curve 0.875). Specifically, the serum estradiol level of 223.15 pg/mL demonstrated a 92.3% sensitive and a 79.3% specificity in predicting AKI of MSAP and SAP patients, respectively. Conclusions: High baseline serum estradiol level appears to be an independent risk factor for AKI in patients with MSAP and SAP. It also tends to be an appropriate indicator for AKI.

Machine learning predictive models for acute pancreatitis: A systematic review.

INTRODUCTION: Acute pancreatitis (AP) is a common clinical pancreatic disease. Patients with different severity levels have different clinical outcomes. With the advantages of algorithms, machine learning (ML) has gradually emerged in the field of disease prediction, assisting doctors in decision-making. METHODS: A systematic review was conducted using the PubMed, Web of Science, Scopus, and Embase databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication time was limited from inception to 29 May 2021. Studies that have used ML to establish predictive tools for AP were eligible for inclusion. Quality assessment of the included studies was conducted in accordance with the IJMEDI checklist. RESULTS: In this systematic review, 24 of 2,913 articles, with a total of 8,327 patients and 47 models, were included. The studies could be divided into five categories: 10 studies (42%) reported severity prediction; 10 studies (42%), complication prediction; 3 studies (13%), mortality prediction; 2 studies (8%), recurrence prediction; and 2 studies (8%), surgery timing prediction. ML showed great accuracy in several prediction tasks. However, most of the included studies were retrospective in nature, conducted at a single centre, based on database data, and lacked external validation. According to the IJMEDI checklist and our scoring criteria, two studies were considered to be of high quality. Most studies had an obvious bias in the quality of data preparation, validation, and deployment dimensions. CONCLUSION: In the prediction tasks for AP, ML has shown great potential in assisting decision-making. However, the existing studies still have some deficiencies in the process of model construction. Future studies need to optimize the deficiencies and further evaluate the comparability of the ML systems and model performance, so as to consequently develop high-quality ML-based models that can be used in clinical practice.

Risk factor analysis and nomogram development for steatorrhea in idiopathic chronic pancreatitis.

OBJECTIVES: Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP). METHODS: ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed. RESULTS: There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P < 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P < 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes. CONCLUSIONS: We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.

Impact of Fatty Pancreas on Postoperative Pancreatic Fistulae: A Meta-Analysis.

BACKGROUND: Soft pancreas is widely recognized as an important risk factor for the development of postoperative pancreatic fistula (POPF). Although fatty pancreas (FP) has not been formally defined as a cause of pancreatic fistula, existing research has shown that it can increase the incidence of POPF by increasing pancreatic tenderness; therefore, it may be a potential risk factor. This study aimed to discern whether FP was associated with POPF. METHOD: Two reviewers independently performed literature searches from five electronic databases. According to the established inclusion criteria, we extracted necessary data from the studies that met the criteria for further analysis. We pooled the odds ratios (ORs) from individual studies using a random-effects model to investigate the associations between POPF and the prognosis of FP. RESULT: A total of 11 studies involving 2484 individuals were included. The pooled prevalence of POPF was 18% (95% CI: 12-24%). Body mass index (BMI) was associated with a significantly increased risk of POPF (OR=3.55; 95% CI: 1.83, 6.86; P=0.0002; I²=0). FP was obviously associated with the occurrence of POPF (OR=3.75; 95% CI: 1.64, 8.58; P=0.002; I²=78). CONCLUSION: FP is closely associated with the development of POPF, and the early identification of these high-risk patients can help to reduce the incidence of POPF. SYSTEMATIC REVIEW REGISTRATION: The Registration URL link is (https://www.crd.york.ac.uk/PROSPERO/). The ID is "CRD42021265141".

Diabetic Bone Marrow Cell Injection Accelerated Acute Pancreatitis Progression.

Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 µg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.

Diabetes aggravates acute pancreatitis possibly via activation of NLRP3 inflammasome in db/db mice.

Clinical studies have confirmed that patients with diabetes had an elevated risk of acute pancreatitis (AP) and diabetes was associated with increased severity and mortality in patients with AP. However, these studies failed to prove a cause-and-effect relationship between diabetes and AP. In the present study, we for the first time have evaluated the effects of diabetes on AP by adopting a type 2 diabetes animal model db/db mice and investigated the possible underlying mechanisms. The results showed that in comparison to wide type (WT) mice, db/db mice showed exacerbated pancreatic and pulmonary injuries, elevated serum amylase and lipase levels, increased myeloperoxidase (MPO) expressions in pancreatic and pulmonary tissues as well as increased apoptotic acinar cells after AP induction. Furthermore, we observed that NLRP3 inflammasome in pancreatic tissues was remarkably activated in db/db mice compared with WT mice. In addition, we also found that diabetes could increase the susceptibility of mice to AP. Taken together, our results indicated that diabetes could predispose and aggravate the disease severity of AP potentially via promoting the activation of NLRP3 inflammasome pathway.