|
1
|
Zhang R, Zhu S, Shi L, Zhang H, Xu X, Xiang B, Wang M. Automated machine learning for early prediction of systemic inflammatory response syndrome in acute pancreatitis. BMC Med Inform Decis Mak 2025; 25:167. [PMID: 40247291 PMCID: PMC12007213 DOI: 10.1186/s12911-025-02997-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 04/07/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Systemic inflammatory response syndrome (SIRS) is a frequent and serious complication of acute pancreatitis (AP), often associated with increased mortality. This study aims to leverage automated machine learning (AutoML) algorithms to create a model for the early and precise prediction of SIRS in AP. METHODS This study retrospectively analyzed patients diagnosed with AP across multiple centers from January 2017 to December 2021. Data from the First Affiliated Hospital of Soochow University and Changshu Hospital were used for training and internal validation, while testing was conducted with data from the Second Affiliated Hospital. Predictive models were constructed and validated using the least absolute shrinkage and selection operator (LASSO) and AutoML. A nomogram was developed based on multivariable logistic regression (LR) analysis, and the performance of the models was assessed through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Additionally, the AutoML model's effectiveness and interpretability were assessed through DCA, feature importance, SHapley Additive exPlanation (SHAP) plots, and locally interpretable model-agnostic explanations (LIME). RESULTS A total of 1,224 patients were included, with 812 in the training cohort, 200 in validation, and 212 in testing. SIRS occurred in 33.7% of the training cohort, 34.0% in validation, and 22.2% in testing. AutoML models outperformed traditional LR, with the deep learning (DL) model achieving an area under the ROC curve of 0.843 in the training set, and 0.848 and 0.867 in validation and testing, respectively. CONCLUSION The AutoML model using the DL algorithm is clinically significant for the early prediction of SIRS in AP.
Collapse
Affiliation(s)
- Rufa Zhang
- Department of Gastroenterology, The People's Hospital of Nanchuan, No. 16, Nanda Street, Nanchuan District, Chongqing, 408400, China
| | - Shiqi Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Li Shi
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Changshu No. 1 People's Hospital, Suzhou, Jiangsu, China
| | - Hao Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xiaodan Xu
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Changshu No. 1 People's Hospital, Suzhou, Jiangsu, China
| | - Bo Xiang
- Department of Gastroenterology, The People's Hospital of Nanchuan, No. 16, Nanda Street, Nanchuan District, Chongqing, 408400, China.
| | - Min Wang
- Department of Gastroenterology, The People's Hospital of Nanchuan, No. 16, Nanda Street, Nanchuan District, Chongqing, 408400, China.
| |
Collapse
|
|
2
|
Yang L, He C, Wang W. Association between neutrophil to high-density lipoprotein cholesterol ratio and disease severity in patients with acute biliary pancreatitis. Ann Med 2024; 56:2315225. [PMID: 38335727 PMCID: PMC10860409 DOI: 10.1080/07853890.2024.2315225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 02/02/2024] [Indexed: 02/12/2024] Open
Abstract
BACKGROUND The neutrophil to high-density lipoprotein cholesterol ratio (NHR) is independently associated with the severity of various diseases. However, its association with acute biliary pancreatitis (ABP) remains unknown. METHODS This study included 1335 eligible patients diagnosed with ABP from April 2016 to December 2022. Patients were divided into low- and high-NHR level groups using an optimal cut-off value determined utilizing Youden's index. Multivariate logistic regression analysis was used to investigate the correlation between NHR and ABP severity. Multivariate analysis-based limited restricted cubic spline (RCS) method was used to evaluate the nonlinear relationship between NHR and the risk of developing moderate or severe ABP. RESULTS In this study, multivariate logistic regression analysis indicated an independent association between NHR and ABP severity (p < .001). The RCS analysis showed a linear correlation between NHR and the risk of developing moderate or severe ABP (P for non-linearity > 0.05), and increased NHR was found to be independently associated with a more severe form of the disease. CONCLUSIONS Our study suggests that NHR is a simple and practical independent indicator of disease severity, serving as a potential novel predictor for patients with ABP.
Collapse
Affiliation(s)
- Lin Yang
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Chiyi He
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| | - Wei Wang
- Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui Province, China
| |
Collapse
|
|
3
|
Fu ZH, Zhao ZY, Liang YB, Cheng DY, Luo JM, Jiang HX, Qin SY. Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis. World J Gastroenterol 2024; 30:3996-4010. [PMID: 39351060 PMCID: PMC11438666 DOI: 10.3748/wjg.v30.i35.3996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/17/2024] [Accepted: 08/30/2024] [Indexed: 09/13/2024] Open
Abstract
BACKGROUND The incidence of hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) is steadily increasing in China, becoming the second leading cause of AP. Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies. HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components. However, the impact of metabolic syndrome components on HTG-AP clinical outcomes remains unclear. AIM To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP. METHODS In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University, we collected data on patient demographics, clinical scores, complications, and clinical outcomes. Subsequently, we analyzed the influence of the presence and number of individual metabolic syndrome components, including obesity, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), on the aforementioned parameters in HTG-AP patients. RESULTS This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP, with low HDL-C being the most significant risk factor for clinical outcomes. The risk of complications increased with the number of metabolic syndrome components. Adjusted for age and sex, patients with high-component metabolic syndrome had significantly higher risks of renal failure [odds ratio (OR) = 3.02, 95%CI: 1.12-8.11)], SAP (OR = 5.05, 95%CI: 2.04-12.49), and intensive care unit admission (OR = 6.41, 95%CI: 2.42-16.97) compared to those without metabolic syndrome. CONCLUSION The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTG-AP, making it crucial to monitor these components for effective disease management.
Collapse
Affiliation(s)
- Zhen-Hua Fu
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zi-Yue Zhao
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yao-Bing Liang
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Dong-Yu Cheng
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jian-Ming Luo
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hai-Xing Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shan-Yu Qin
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|
|
4
|
Lee PJ, Papachristou GI, Speake C, Lacy-Hulbert A. Immune markers of severe acute pancreatitis. Curr Opin Gastroenterol 2024; 40:389-395. [PMID: 38967941 PMCID: PMC11305979 DOI: 10.1097/mog.0000000000001053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
PURPOSE OF REVIEW Acute pancreatitis is a common acute inflammatory disorder of the pancreas, and its incidence has been increasing worldwide. Approximately 10% of acute pancreatitis progresses to severe acute pancreatitis (SAP), which carries significant morbidity and mortality. Disordered immune response to pancreatic injury is regarded as a key event that mediates systemic injury in SAP. In this article, we review recent developments in immune biomarkers of SAP and future directions for research. RECENT FINDINGS Given the importance of the NLRP3-inflammasome pathway in mediating systemic inflammatory response syndrome and systemic injury, recent studies have investigated associations of SAP with systemic levels of activators of NLRP3, such as the damage associated molecular patterns (DAMPs) for the first time in human SAP. For example, circulating levels of histones, mitochondrial DNAs, and cell free DNAs have been associated with SAP. A panel of mechanistically relevant immune markers (e.g., panel of Angiopoeitin-2, hepatocyte growth factor, interleukin-8 (IL-8), resistin and sTNF-α R1) carried higher predictive accuracies than existing clinical scores and individual immune markers. Of the cytokines with established relevance to SAP pathogenesis, phase 2 trials of immunotherapies, including tumor necrosis factor (TNF)-alpha inhibition and stimulation of IL-10 production, are underway to determine if altering the immunologic response can reduce the severity of acute pancreatitis (AP). SUMMARY Circulating systemic levels of various DAMPs and a panel of immune markers that possibly reflect activities of different pathways that drive SAP appear promising as predictive biomarkers for SAP. But larger multicenter studies are needed for external validation. Studies investigating immune cellular pathways driving SAP using immunophenotyping techniques are scarce. Interdisciplinary efforts are also needed to bring some of the promising biomarkers to the bedside for validation and testing for clinical utility. Studies investigating the role of and characterization of altered gut-lymph and gut-microbiota in severe AP are needed.
Collapse
Affiliation(s)
- Peter J Lee
- Division of Gastroenterology, Hepatology, and Nutrition. Ohio State University Wexner Medical Center, Columbus, OH
| | - Georgios I Papachristou
- Division of Gastroenterology, Hepatology, and Nutrition. Ohio State University Wexner Medical Center, Columbus, OH
| | - Cate Speake
- Center for Interventional Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington
| | - Adam Lacy-Hulbert
- Center for Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington
| |
Collapse
|
|
5
|
Tsomidis I, Voumvouraki A, Kouroumalis E. The Pathogenesis of Pancreatitis and the Role of Autophagy. GASTROENTEROLOGY INSIGHTS 2024; 15:303-341. [DOI: 10.3390/gastroent15020022] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce and perpetuate pancreatitis were presented. As autophagy is now considered a fundamental mechanism in the pathophysiology of both acute and chronic pancreatitis, the fundamentals of the autophagy pathway were discussed to allow for a better understanding of the pathophysiological mechanisms of pancreatitis. The various aspects of pathogenesis, including trypsinogen activation, ER stress and mitochondrial dysfunction, the implications of inflammation, and macrophage involvement in innate immunity, as well as the significance of pancreatic stellate cells in the development of fibrosis, were also analyzed. Recent findings on exosomes and the miRNA regulatory role were also presented. Finally, the role of autophagy in the protection and aggravation of pancreatitis and possible therapeutic implications were reviewed.
Collapse
Affiliation(s)
- Ioannis Tsomidis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
| | - Argyro Voumvouraki
- 1st Department of Internal Medicine, AHEPA University Hospital, 54621 Thessaloniki, Greece
| | - Elias Kouroumalis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
| |
Collapse
|
|
6
|
Jakkampudi A, Sarkar P, Unnisa M, Patil A, Koutarapu C, Jaggaiahgari S, Naik P, Sarkar S, Prasanna A, Chintaluri S, Reddy DN, Beedu SR, Talukdar R. Kynurenine pathway alteration in acute pancreatitis and its role as a biomarker of infected necrosis. Pancreatology 2023; 23:589-600. [PMID: 37438173 DOI: 10.1016/j.pan.2023.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/18/2023] [Accepted: 07/04/2023] [Indexed: 07/14/2023]
Abstract
INTRODUCTION Infected pancreatic necrosis (IPN) is a major cause of mortality in acute pancreatitis (AP). Currently, no specific strategies are available to predict the development of IPN. Earlier we reported that persistent down-regulation of HLA-DR increases risk of developing IPN. Altered kynurenine pathway (KP) metabolites showed poor prognosis in sepsis. Here we evaluated the role of HLA-DR and KP in IPN. METHODS Patients with ANP and healthy controls were enrolled. Demographic and clinical parameters were recorded. Circulating interleukin (IL)-8, 6, 1β, 10, Tumor necrosis factor-α were quantified using flowcytometry. Plasma procalcitonin, endotoxin, and KP (tryptophan, kynurenine) concentrations were estimated using ELISA. qRT-PCR was conducted to evaluate mRNA expression of HLA-DR, IL-10, Toll like receptor-4 (TLR-4), and kynurenine-3-monooxygenase (KMO) genes on peripheral blood mononuclear cells. Plasma metabolites were quantified using gas chromatography mass spectrometry (GC-MS/MS). Standard statistical methods were used to compare study groups. Metaboanalyst was used to analyse/visualize the metabolomics data. RESULTS We recruited 56 patients in Cohort-1 (IPN:26,Non-IPN:30), 78 in Cohort-2 (IPN:57,Non-IPN:21), 26 healthy controls. Increased cytokines, endotoxin, and procalcitonin were observed in patients with IPN compared to Non-IPN. HLA-DR and KMO gene expressions were significantly down-regulated in IPN groups, showed positive correlation with one another but negatively correlated with IL-6 and endotoxin concentrations. Increased IDO and decreased plasma tryptophan were observed in IPN patients. Metabolome analysis showed significant reduction in several essential amino acids including tryptophan in IPN patients. Tryptophan, at a concentration of 9 mg/ml showed an AUC of 91.9 (95%CI 86.5-97.4) in discriminating IPN. CONCLUSION HLA-DR downregulation and KP alteration are related to IPN. The KP metabolite plasma tryptophan can act as a potential biomarker for IPN.
Collapse
Affiliation(s)
- Aparna Jakkampudi
- Wellcome DBT India Alliance Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, India
| | - Priyanka Sarkar
- Wellcome DBT India Alliance Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, India
| | - Misbah Unnisa
- Pancreas Clinic, Dept. of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Aashish Patil
- Pancreas Clinic, Dept. of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Chandrakanth Koutarapu
- Pancreas Clinic, Dept. of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Shashidhar Jaggaiahgari
- Wellcome DBT India Alliance Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, India
| | - Pragathi Naik
- Dept. of Transfusion Medicine, Asian Institute of Gastroenterology, Hyderabad, India
| | - Subhaleena Sarkar
- Wellcome DBT India Alliance Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, India
| | - Ambika Prasanna
- Wellcome DBT India Alliance Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, India
| | - Sreelekha Chintaluri
- Wellcome DBT India Alliance Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, India
| | - D Nageshwar Reddy
- Pancreas Clinic, Dept. of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | | | - Rupjyoti Talukdar
- Wellcome DBT India Alliance Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, India; Pancreas Clinic, Dept. of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India.
| |
Collapse
|
|
7
|
Huang L, Zeng Y, Duan L, Zhuang Q, Zhou Y, Wang L, Chen L, Liu X, Xiong Y. Optimal timing of free total rhubarb anthraquinones on immune regulation in rats with severe acute pancreatitis. JOURNAL OF ETHNOPHARMACOLOGY 2023; 308:116266. [PMID: 36806482 DOI: 10.1016/j.jep.2023.116266] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 06/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhubarb is the peeled and dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of anti-inflammation and immunological modulation. The timing of immune regulation is a major problem in the immunotherapy for severe acute pancreatitis (SAP). several studies reported that FTRAs could reduce systemic inflammatory responses by inhibiting early immune overactivity in the gut in rats with SAP. But, the optimal timing of rhubarb and FTRAs administration is not clear in clinical practice. Therefore, the time window for the best efficacy of rhubarb and FTRAs in the treatment of SAP patients should be further elucidated. AIM OF THE STUDY The main purpose of the present study was to evaluate the efficacy and optimal timing of immune modulation with FTRAs in the treatment of SAP in rats. MATERIALS AND METHODS FTRAs (22.5, 45 and 90 mg/kg), Rhubarb (RHU) (900 mg/kg, positive control) or normal saline (vehicle control) were initiated at 0 (immediately), 48 and 72 h every 12 h for three times in total. The therapeutic effects of FTRAs and RHU on pancreas and intestinal tissues injury, secondary infection with pseudomonas aeruginosa (PA), amylase, lipase, D-lactic acid (DLA), endotoxin (ET), proinflammatory and anti-inflammatory cytokines, macrophages, dendritic cells and regulatory T cells (Tregs) in the blood, small intestine and/or mesenteric lymph node (MLN) were determined in rats with SAP after treatment. RESULTS The results showed that administration of FTRAs at 0 h was superior to 48 h and 72 h, which significantly protected the injury of pancreas and intestinal tissues, reduced the mortality induced by secondary infection with PA, decreased the levels of amylase, lipase, DLA, ET, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, IL-8, IL-18 and Tregs, and increased the levels of IL-4, sTNF-αR, macrophages and dendritic cells, secretary immunoglobulin A (SIgA) in the blood and/or small intestinal tissues in rats with SAP. CONCLUSIONS In conclusion, our studies indicate that the treatment window of FTRAs for SAP is within 48 h of development, administration of FTRAs at the early stage (0 h, immune overreaction period) was the optimal time and superior to that of 48 h and 72 h for its therapeutic efficacy. The earlier the administration of FTRAs, the better the therapeutic efficacy. Therefore, our data may provide a scientific rationale for the clinical application and optimal timing of FTRAs in the treatment of SAP.
Collapse
Affiliation(s)
- Liqiang Huang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China; Department of Pharmacy, Second People's Hospital of Yibin, Yibin, 644000, China
| | - Yue Zeng
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Lingjing Duan
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Qian Zhuang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Yejiang Zhou
- Department of Gastrointestinal Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Lulu Wang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Li Chen
- Department of Pharmacy, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Xingyu Liu
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Yuxia Xiong
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.
| |
Collapse
|
|
8
|
Kostenko V, Akimov O, Gutnik O, Kostenko H, Kostenko V, Romantseva T, Morhun Y, Nazarenko S, Taran O. Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response. Heliyon 2023; 9:e15551. [PMID: 37180884 PMCID: PMC10171461 DOI: 10.1016/j.heliyon.2023.e15551] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 03/09/2023] [Accepted: 04/13/2023] [Indexed: 05/16/2023] Open
Abstract
One of the adverse outcomes of acute inflammatory response is progressing to the chronic stage or transforming into an aggressive process, which can develop rapidly and result in the multiple organ dysfunction syndrome. The leading role in this process is played by the Systemic Inflammatory Response that is accompanied by the production of pro- and anti-inflammatory cytokines, acute phase proteins, and reactive oxygen and nitrogen species. The purpose of this review that highlights both the recent reports and the results of the authors' own research is to encourage scientists to develop new approaches to the differentiated therapy of various SIR manifestations (low- and high-grade systemic inflammatory response phenotypes) by modulating redox-sensitive transcription factors with polyphenols and to evaluate the saturation of the pharmaceutical market with appropriate dosage forms tailored for targeted delivery of these compounds. Redox-sensitive transcription factors such as NFκB, STAT3, AP1 and Nrf2 have a leading role in mechanisms of the formation of low- and high-grade systemic inflammatory phenotypes as variants of SIR. These phenotypic variants underlie the pathogenesis of the most dangerous diseases of internal organs, endocrine and nervous systems, surgical pathologies, and post-traumatic disorders. The use of individual chemical compounds of the class of polyphenols, or their combinations can be an effective technology in the therapy of SIR. Administering natural polyphenols in oral dosage forms is very beneficial in the therapy and management of the number of diseases accompanied with low-grade systemic inflammatory phenotype. The therapy of diseases associated with high-grade systemic inflammatory phenotype requires medicinal phenol preparations manufactured for parenteral administration.
Collapse
Affiliation(s)
- Vitalii Kostenko
- Poltava State Medical University, Department of Pathophysiology, Ukraine
| | - Oleh Akimov
- Poltava State Medical University, Department of Pathophysiology, Ukraine
- Corresponding author.
| | - Oleksandr Gutnik
- Poltava State Medical University, Department of Pathophysiology, Ukraine
| | - Heorhii Kostenko
- Poltava State Medical University, Department of Pathophysiology, Ukraine
| | - Viktoriia Kostenko
- Poltava State Medical University, Department of Foreign Languages with Latin and Medical Terminology, Ukraine
| | - Tamara Romantseva
- Poltava State Medical University, Department of Pathophysiology, Ukraine
| | - Yevhen Morhun
- Poltava State Medical University, Department of Pathophysiology, Ukraine
| | - Svitlana Nazarenko
- Poltava State Medical University, Department of Pathophysiology, Ukraine
| | - Olena Taran
- Poltava State Medical University, Department of Pathophysiology, Ukraine
| |
Collapse
|
|
9
|
Liu S, Luo W, Szatmary P, Zhang X, Lin JW, Chen L, Liu D, Sutton R, Xia Q, Jin T, Liu T, Huang W. Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19. Int J Mol Sci 2023; 24:3246. [PMID: 36834656 PMCID: PMC9964039 DOI: 10.3390/ijms24043246] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.
Collapse
Affiliation(s)
- Shiyu Liu
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wenjuan Luo
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Peter Szatmary
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BE, UK
| | - Xiaoying Zhang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jing-Wen Lin
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Lu Chen
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Dan Liu
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Robert Sutton
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BE, UK
| | - Qing Xia
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Tao Jin
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Tingting Liu
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wei Huang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| |
Collapse
|
|
10
|
Liu S, Szatmary P, Lin JW, Wang Q, Sutton R, Chen L, Liu T, Huang W, Xia Q. Circulating monocytes in acute pancreatitis. Front Immunol 2022; 13:1062849. [PMID: 36578487 PMCID: PMC9791207 DOI: 10.3389/fimmu.2022.1062849] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022] Open
Abstract
Acute pancreatitis is a common gastrointestinal disease characterized by inflammation of the exocrine pancreas and manifesting itself through acute onset of abdominal pain. It is frequently associated with organ failure, pancreatic necrosis, and death. Mounting evidence describes monocytes - phagocytic, antigen presenting, and regulatory cells of the innate immune system - as key contributors and regulators of the inflammatory response and subsequent organ failure in acute pancreatitis. This review highlights the recent advances of dynamic change of numbers, phenotypes, and functions of circulating monocytes as well as their underling regulatory mechanisms with a special focus on the role of lipid modulation during acute pancreatitis.
Collapse
Affiliation(s)
- Shiyu Liu
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Peter Szatmary
- Liverpool Pancreatitis Research Group, Liverpool University Hospitals NHS Foundation Trust and Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Jing-wen Lin
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Qiqi Wang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Robert Sutton
- Liverpool Pancreatitis Research Group, Liverpool University Hospitals NHS Foundation Trust and Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Lu Chen
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Tingting Liu
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China,*Correspondence: Tingting Liu, ; Wei Huang, ; Qing Xia,
| | - Wei Huang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China,Institutes for Systems Genetics & Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China,*Correspondence: Tingting Liu, ; Wei Huang, ; Qing Xia,
| | - Qing Xia
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China,*Correspondence: Tingting Liu, ; Wei Huang, ; Qing Xia,
| |
Collapse
|
|
11
|
Wang D, Lu J, Zhang P, Hu Z, Shi Y. Relationship between blood glucose levels and length of hospital stay in patients with acute pancreatitis: An analysis of MIMIC-III database. Clin Transl Sci 2022; 16:246-257. [PMID: 36350303 PMCID: PMC9926064 DOI: 10.1111/cts.13445] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/11/2022] [Accepted: 10/20/2022] [Indexed: 11/10/2022] Open
Abstract
We aimed to investigate the effect of blood glucose levels on length of stay (LOS) in patients hospitalized with acute pancreatitis (AP). We retrospectively collected clinical data of patients diagnosed with AP from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Dose-response analysis curves of restricted cubic spline (RCS) function and multivariate logistic regression models were used to confirm the relationship between blood glucose levels and LOS. A total of 3656 patients with AP were included according to the inclusion and exclusion criteria. According to RCS, all patients were divided into three groups, namely the less than 68 mg/dl group, the 68-104 mg/dl group, and the >104 mg/dl group. RCS showed a significant nonlinear correlation between blood glucose levels and LOS (p < 0.001). Multivariate logistic regression revealed a 53% higher risk of LOS greater than or equal to 2 days (adjusted odds ratio [aOR] = 1.53, 95% confidence interval [CI] 1.24-1.89, p < 0.001), a 114% higher risk of LOS greater than or equal to 5 days (aOR = 2.14, 95% CI 1.86-2.47, p < 0.001), and a 130% higher risk of LOS greater than or equal to 7 days (aOR = 2.30, 95% CI 1.97-2.69, p < 0.001) in patients with glucose levels greater than 104 mg/dl than patients with glucose levels 68-104 mg/dl. The risk of LOS greater than or equal to 7 days was higher in patients with blood glucose less than 68 mg/dl than patients with glucose levels 68-104 mg/dl (aOR = 1.45, 95% CI 1.02-2.05, p = 0.040). In addition, we observed similar results in many subgroups. Our findings suggest that either hyperglycemia or hypoglycemia increase LOS in patients hospitalized with AP. For hospitalized patients with AP, blood glucose control in a reasonable range of 68-104 mg/dl is required.
Collapse
Affiliation(s)
- Dongyan Wang
- Department of GastroenterologyShanghai Pudong New Area Gongli HospitalShanghaiChina
| | - Jie Lu
- Department of GastroenterologyShanghai Pudong New Area Gongli HospitalShanghaiChina
| | - Pan Zhang
- Department of LaboratoryShanghai Pudong New Area Gongli HospitalShanghaiChina
| | - Zhengyu Hu
- Department of General Surgery, Shanghai Tenth People's HospitalAffiliated to Tongji University School of MedicineShanghaiChina
| | - Yihai Shi
- Department of GastroenterologyShanghai Pudong New Area Gongli HospitalShanghaiChina
| |
Collapse
|
|
12
|
Kinjoh K, Nagamura R, Sakuda Y, Yamauchi S, Takushi H, Iraha T, Idomari K. Clinical efficacy of blood purification using a polymethylmethacrylate hemofilter for the treatment of severe acute pancreatitis. Acute Crit Care 2022; 37:398-406. [PMID: 35791651 PMCID: PMC9475162 DOI: 10.4266/acc.2022.00192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/30/2022] [Indexed: 11/30/2022] Open
Abstract
Background Severe acute pancreatitis (SAP) is a systemic inflammatory disease, and it can often complicate into acute kidney injury (AKI) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study aimed to evaluate the clinical effectiveness of blood purification using a polymethylmethacrylate (PMMA) hemofilter. Methods We retrospectively examined 54 patients, who were diagnosed with SAP according to the Japanese criteria from January 2011 to December 2019. Results Of a total of 54 SAP patients, 26 patients progressively developed AKI and required continuous hemodialysis with a PMMA membrane hemofilter (PMMA-CHD). Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were significantly higher in patients requiring PMMA-CHD than in patients not requiring hemodialysis. The lung injury scores were also significantly higher in patients requiring PMMA-CHD. Of the 26 patients, 16 patients developed ALI/ARDS and required mechanical ventilation. A total of seven patients developed severe ALI/ARDS and received additional intermittent hemodiafiltration using a PMMA hemofilter (PMMA-HDF). Although the length of intensive care unit stay was significantly longer in patients with severe ALI/ARDS, blood purification therapy was discontinued in all the patients. The survival rates at the time of discharge were 92.3% and 92.9% in patients with and without PMMA-CHD, respectively. These real mortality ratios were obviously lower than the estimated mortality ratios predicted by APACHE II scores. Conclusions These finding suggest that the blood purification using a PMMA hemofilter would be effective for the treatment of AKI and ALI/ARDS in SAP patients.
Collapse
|
|
13
|
Zhuang Q, Huang L, Zeng Y, Wu X, Qiao G, Liu M, Wang L, Zhou Y, Xiong Y. Dynamic Monitoring of Immunoinflammatory Response Identifies Immunoswitching Characteristics of Severe Acute Pancreatitis in Rats. Front Immunol 2022; 13:876168. [PMID: 35663952 PMCID: PMC9160235 DOI: 10.3389/fimmu.2022.876168] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/21/2022] [Indexed: 11/30/2022] Open
Abstract
Background Immune dysfunction is the main characteristic of severe acute pancreatitis (SAP), and the timing of immune regulation has become a major challenge for SAP treatment. Previous reports about the time point at which the immune status of SAP changed from excessive inflammatory response to immunosuppression (hypo-inflammatory response) are conflicting. Purposes The aims of this study are to explore the immunological dynamic changes in SAP rats from the perspective of intestinal mucosal immune function, and to determine the immunoswitching point from excessive inflammatory response to immunosuppression. Methods Retrograde injection of sodium taurocholate into the pancreaticobiliary duct was applied to establish a SAP model in rats. The survival rate and the activities of serum amylase and pancreatic lipase in SAP rats were measured at different time points after model construction. The pathological changes in the pancreas and small intestines were analyzed, and the levels of intestinal pro- and anti-inflammatory cytokines and the numbers of intestinal macrophages, dendritic cells, Th1, Th2, and T regulatory cells were assessed. Meanwhile, the SAP rats were challenged with Pseudomonas aeruginosa (PA) strains to simulate a second hit, and the levels of intestinal inflammatory cytokines and the numbers of immune cells were analyzed to confirm the immunoswitching point. Results The time periods of 12–24 h and 48–72 h were the two death peaks in SAP rats. The pancreas of SAP rats showed self-limiting pathological changes, and the switching period of intestinal cytokines, and innate and adaptive immunity indexes occurred at 24–48 h. It was further confirmed that 48 h after SAP model construction was the immunoswitching point from excessive inflammatory response to immunosuppression. Conclusion The SAP rats showed characteristics of intestinal mucosal immune dysfunction after model construction, and the 48th h was identified as the immunoswitching point from excessive inflammatory response to immunosuppression. The results are of great significance for optimizing the timing of SAP immune regulation.
Collapse
Affiliation(s)
- Qian Zhuang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Liqiang Huang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.,Institute for Clinical Trials of Drugs, Second People's Hospital of Yibin, Yibin, China
| | - Yue Zeng
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xu Wu
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Gan Qiao
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Minghua Liu
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Lulu Wang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yejiang Zhou
- Department of Gastrointestinal Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yuxia Xiong
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| |
Collapse
|
|
14
|
Han T, Cheng T, Liao Y, He Y, Liu B, Lai Q, Pan P, Liu J, Cao Y, Yu H. The ratio of red blood cell distribution width to serum calcium predicts severity of patients with acute pancreatitis. Am J Emerg Med 2022; 53:190-195. [DOI: 10.1016/j.ajem.2022.01.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
15
|
Li Y, Zheng R, Gao F, Wang L, Feng S, Li J, Huang Z. Association between high-density lipoprotein cholesterol and apolipoprotein A-I and severe acute pancreatitis: a case-control study. Eur J Gastroenterol Hepatol 2021; 33:1517-1523. [PMID: 34723873 DOI: 10.1097/meg.0000000000002095] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Evidence is limited concerning the association between serum concentrations of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (APO A-I) and severe acute pancreatitis (SAP). This study was designed to explore whether HDL-C and APO A-I were independently correlated to SAP after adjusting for covariates. METHODS There were 1127 patients with acute pancreatitis who were recruited from a tertiary teaching hospital in Wenzhou from 1 January 2018 to 30 April 2020. The independent variables were baseline levels of HDL-C, and APO A-I collected within 24 h after admission. The dependent variable was the occurrence of SAP during hospitalization. Univariate and multivariate binary logistic regression were conducted to analyze the relationship between HDL-C and APO A-I and SAP. The receiver operating characteristic curve was applied to analyze the prediction power of lipid parameters and C-reactive protein for SAP. RESULTS The incidence of SAP was 11.5% among the 678 patients included in the final analysis. The serum levels of APO A-I and HDL-C were negatively related to SAP after adjusting for confounders with an odds ratio of 0.24 [95% confidence interval (CI): 0.06-0.95] and 0.16 (95% CI, 0.04-0.56), respectively. APO A-I (area under the curve = 0.69; 95% CI, 0.63-0.76) and HDL-C (area under the curve = 0.72; 95% CI, 0.66-0.79) showed higher predictive value for SAP compared with other lipid parameters. CONCLUSIONS Decreased serum concentrations of HDL-C and APO A-I are associated with SAP after adjusting for covariates.
Collapse
Affiliation(s)
| | - Rui Zheng
- Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | | | - Li Wang
- Department of Gastroenterology
| | | | - Jie Li
- Department of Gastroenterology
| | | |
Collapse
|
|
16
|
Nalisa M, Nweke EE, Smith MD, Omoshoro-Jones J, Devar JWS, Metzger R, Augustine TN, Fru PN. Chemokine receptor 8 expression may be linked to disease severity and elevated interleukin 6 secretion in acute pancreatitis. World J Gastrointest Pathophysiol 2021; 12:115-133. [PMID: 34877026 PMCID: PMC8611186 DOI: 10.4291/wjgp.v12.i6.115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 07/08/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute pancreatitis (AP) is an inflammatory disease, which presents with epigastric pain and is clinically diagnosed by amylase and lipase three times the upper limit of normal. The 2012 Atlanta classification stratifies the severity of AP as one of three risk categories namely, mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP). Challenges in stratifying AP upon diagnosis suggest that a better understanding of the underlying complex pathophysiology may be beneficial. AIM To identify the role of the chemokine receptor 8 (CCR8), expressed by T-helper type-2 Lymphocytes and peritoneal macrophages, and its possible association to Interleukin (IL)-6 and AP stratification. METHODS This study was a prospective case-control study. A total of 40 patients were recruited from the Chris Hani Baragwanath Academic Hospital and the Charlotte Maxeke Johannesburg Academic Hospital. Bioassays were performed on 29 patients (14 MAP, 11 MSAP, and 4 SAP) and 6 healthy controls as part of a preliminary study. A total of 12 mL of blood samples were collected at Day (D) 1, 3, 5, and 7 post epigastric pain. Using multiplex immunoassay panels, real-time polymerase chain reaction (qRT-PCR) arrays, and multicolour flow cytometry analysis, immune response-related proteins, genes, and cells were profiled respectively. GraphPad Prism™ software and fold change (FC) analysis was used to determine differences between the groups. P<0.05 was considered significant. RESULTS The concentration of IL-6 was significantly different at D3 post epigastric pain in both the MAP group and MSAP group with P = 0.001 and P = 0.013 respectively, in a multiplex assay. When a FC of 2 was applied to identify differentially expressed genes using RT2 Profiler, CCR8 was shown to increase steadily with disease severity from MAP (1.33), MSAP (38.28) to SAP (1172.45) median FC. Further verification studies using RT-PCR showed fold change increases of CCR8 in MSAP and SAP ranging from 1000 to 1000000 times when represented as Log10, compared to healthy control respectively at D3. The findings also showed differing lymphocyte and monocyte cell frequency between the groups. With monocyte population frequency as high as 70% in MSAP at D3. CONCLUSION The higher levels of CCR8 and IL-6 in the severe patients and immune cell differences compared to MAP and controls provide an avenue for exploring AP stratification to improve management.
Collapse
Affiliation(s)
- Mwangala Nalisa
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
| | - Ekene Emmanuel Nweke
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
| | - Martin D Smith
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
- Department of Surgery, Chris Hani Baragwanath Academic Hospital, Johannesburg 1864, Gauteng, South Africa
| | - Jones Omoshoro-Jones
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
- Department of Surgery, Chris Hani Baragwanath Academic Hospital, Johannesburg 1864, Gauteng, South Africa
| | - John WS Devar
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
- Department of Surgery, Chris Hani Baragwanath Academic Hospital, Johannesburg 1864, Gauteng, South Africa
| | - Rebecca Metzger
- Institut für Immunologie, Ludwig-Maximilians-Universität München, München 80539, Germany
| | - Tanya N Augustine
- School of Anatomical Sciences, Faculty of Health Science, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
| | - Pascaline N Fru
- Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
| |
Collapse
|
|
17
|
Gut microbiome linked to pancreatitis. CURRENT OPINION IN PHYSIOLOGY 2021. [DOI: 10.1016/j.cophys.2021.100470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
18
|
WITHDRAWN: The ratio of red blood cell distribution width to serum calcium predicts severity of patients with acute pancreatitis. Am J Emerg Med 2021. [DOI: 10.1016/j.ajem.2021.08.049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
|
|
19
|
Piao X, Sui X, Liu B, Cui T, Qi Z. Picroside II Improves Severe Acute Pancreatitis-Induced Hepatocellular Injury in Rats by Affecting JAK2/STAT3 Phosphorylation Signaling. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9945149. [PMID: 34368363 PMCID: PMC8337114 DOI: 10.1155/2021/9945149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 06/03/2021] [Accepted: 07/04/2021] [Indexed: 11/17/2022]
Abstract
Picroside II is an important ingredient agent in Traditional Chinese medicine and hoped to reduce hepatocellular injury caused by severe acute pancreatitis (SAP). An SAP-induced hepatocellular injury model was established in rats by using pentobarbital sodium. 27 rats were divided into 3 groups: the sham group (SG), model group (MG), and Picroside groups (PG). SAP-induced hepatocellular injury was assessed using hematoxylin and eosin staining. We measured hepatocellular enzymes (amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)), oxidative stress factors (superoxidase dismutase (SOD) and malondialdehyde (MDA)), and inflammatory factors (tumor necrosis factor α (TNF-α), interleukin- (IL-) 6, and IL-10), apoptotic factors (BAX and cleaved caspase 3), and inflammatory signaling (Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), p-JAK2, and p-STAT3) in hepatocellular tissues. The SAP-induced hepatocellular injury model was successfully established. Picroside II treatment repaired hepatocellular injury by reducing the activities of AMY, ALT, and AST; reducing the levels of MDA, TNF-α, IL-1, IL-6, p-JAK2, p-STAT3, BAX, and cleaved caspase 3; and increasing the levels of SOD and IL-10. Picroside II exerted protective function for the SAP-induced hepatocellular injury model. Picroside II improved SAP-induced hepatocellular injury and antioxidant and anti-inflammatory properties by affecting JAK2/STAT3 phosphorylation signaling.
Collapse
Affiliation(s)
- Xuehua Piao
- Department of Traditional Chinese Medicine, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121001, China
| | - Xiaodan Sui
- Department of Hepatology, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun 130021, China
| | - Baohai Liu
- Department of Gastroenterology, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121001, China
| | - Tingfang Cui
- Department of Gastroenterology, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121001, China
| | - Zinan Qi
- Department of Gastroenterology, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121001, China
| |
Collapse
|
|
20
|
Lee PJ, Papachristou GI. Early Prediction of Severity in Acute Pancreatitis. CLINICAL PANCREATOLOGY FOR PRACTISING GASTROENTEROLOGISTS AND SURGEONS 2021:31-39. [DOI: 10.1002/9781119570097.ch4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
21
|
Li HP, He X, Zhang L, Li CX, Li SQ, Li QY. Therapeutic Agents Rounding Up the Immunopathology of COVID-19. Ther Clin Risk Manag 2021; 17:657-668. [PMID: 34234442 PMCID: PMC8254585 DOI: 10.2147/tcrm.s313003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/10/2021] [Indexed: 12/12/2022] Open
Abstract
COVID-19 pandemic has caused more than 3 million deaths globally during the past year. The direct attack from SARS-CoV-2 and hyperactivated immune response contribute to the progress and deterioration of COVID-19. After the virus invades, the activation and release of cytokines/chemokines cause "cytokine storm", leading to acute respiratory distress syndrome (ARDS) and multiple organs dysfunction syndrome (MODS). Eliminating virus and blocking cytokines are important checkpoints of COVID-19 therapy, and several agents targeting immunopathology, including interferons, thymosin, glucocorticoids and immunoglobulin, have shown therapeutic effects in severe patients with COVID-19. Herein, we reviewed the practice evidences and concluded that several agents rounding up the immunopathology of COVID-19 may be the alternative approaches under the scenario of the lacking of effective antiviral drugs.
Collapse
Affiliation(s)
- Hong Peng Li
- Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Institute of Respiratory Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Xuan He
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Liu Zhang
- Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Institute of Respiratory Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Chuan Xiang Li
- Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Institute of Respiratory Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Department of Respiratory Medicine, Wuhan No.3 Hospital, Wuhan, 430000, People’s Republic of China
| | - Shi Qi Li
- Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Institute of Respiratory Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| | - Qing Yun Li
- Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
- Institute of Respiratory Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China
| |
Collapse
|
|
22
|
Talukdar R, Tsuji Y, Jagtap N, Pradeep R, Rao GV, Reddy DN. Non-compliance to practice guidelines still exist in the early management of acute pancreatitis: Time for reappraisal? Pancreatology 2021; 21:S1424-3903(21)00471-3. [PMID: 34049823 DOI: 10.1016/j.pan.2021.05.301] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/26/2021] [Accepted: 05/13/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Earlier national surveys on the management of acute pancreatitis (AP) had reported non-compliance to practice guidelines. In the past decade, several guidelines were revised based on new evidence. In this multicenter international survey, we aimed to evaluate the practice patterns of early management of AP and compliance to the revised treatment guidelines across different disciplines and practice environments. METHODS A structured questionnaire was sent via email to a target population of 654 that constituted of medical and surgical gastroenterologists, physicians and general surgeons, paediatricians from academic and non-academic centres across 30 countries. Other than demographic variables, the questionnaire contained items pertaining to early management of AP, such as, assessment at admissions and within first 72 h s, details regarding analgesics, IV hydration, oral/enteral feeding and antibiotic use. RESULTS The response rate was 46.2% and after exclusions, a total of 297 participant's responses were analysed. Majority of the participants were from Asia, followed by Europe and the Americas. 181 (60.9%) claimed to follow practice guidelines, out of which 59 (32.6%) followed more than one. On further probing, only 41.9% were actually compliant to feeding and 59.7% to antibiotic guidelines. Even though participants opted for aggressive hydration, early feeding and avoidance of prophylactic antibiotics, there were non-compliance and discrepancies in titration of fluid therapy, indications of feeding and antibiotic use. DISCUSSION Discrepancies and non-compliance still appear to exist in the early management of AP due to lack of strong evidence. We discuss ways that could improve compliance to the existing guidelines until stronger evidence comes to the fore.
Collapse
Affiliation(s)
- Rupjyoti Talukdar
- Dept. of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India; Wellcome-DBT Indian Alliance Labs., Institute of Basic and Translational Research, Asian Healthcare Foundation, Hyderabad, India.
| | - Yoshihisa Tsuji
- Dept. of General Medicine, Sapporo Medical University, Japan
| | - Nitin Jagtap
- Dept. of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - R Pradeep
- Dept. of Surgical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - G V Rao
- Dept. of Surgical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - D Nageshwar Reddy
- Dept. of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| |
Collapse
|
|
23
|
Abstract
Purpose of review There have been significant advancements in different aspects of management of severe acute pancreatitis (SAP). Our review of the most recent literature focuses on severity prediction, fluid resuscitation, analgesic administration, nutrition, and endoscopic intervention for SAP and its extra-pancreatic complications. Recent findings Recent studies on serum cytokines for the prediction of SAP have shown superior prognostic performance when compared with conventional laboratory tests and clinical scoring systems. In patients with established SAP and vascular leak syndrome, intravenous fluids should be administered with caution to prevent intra-abdominal hypertension and volume overload. Endoscopic retrograde cholangiopancreatography improves outcomes only in AP patients with suspected cholangitis. Early enteral tube-feeding does not appear to be superior to on-demand oral feeding. Abdominal compartment syndrome is a highly lethal complication of SAP that requires percutaneous drainage or decompressive laparotomy. Endoscopic transmural drainage followed by necrosectomy (i.e., “step-up approach”) is the treatment strategy of choice in patients with symptomatic or infected walled-off pancreatic necrosis. Summary SAP is a complex clinical syndrome associated with a high mortality rate. Early prediction of SAP remains challenging due to the limited accuracy of the available prediction tools. Early fluid resuscitation, organ support, enteral nutrition, and prevention of/or prompt recognition of abdominal compartment syndrome remain cornerstones of its management. A step-up, minimally invasive drainage/debridement is the preferred approach for patients with infected pancreatic necrosis.
Collapse
Affiliation(s)
- Peter J. Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA USA
| | - Georgios I. Papachristou
- Division of Gastroenterology and Hepatology, Department of Medicine, Ohio State University Wexner Medical Center, 410 W 10th Street, 2nd floor, Columbus, OH 43210 USA
| |
Collapse
|
|
24
|
Lorenz D, Maurer F, Philipp D, Albrecht F, Hüppe T, Sessler DI, Wolf B, Volk T, Kreuer S, Fink T. Changes in volatile organic compounds provoked by lipopolysaccharide- or alpha toxin-induced inflammation in ventilated rats. J Breath Res 2020; 15:016003. [PMID: 33103661 DOI: 10.1088/1752-7163/abb449] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Inflammation may alter volatile organic compounds (VOCs) in exhaled breath. We therefore used ion mobility spectrometry (IMS) to evaluate exhaled breath components in two non-infectious inflammatory models. Fifty male Sprague Dawley rats were anesthetized and ventilated for 24 h. Five treatments were randomly assigned: (1) lipopolysaccharide low dose [5 mg/kg]; (2) lipopolysaccharide high dose [10 mg/kg]; (3) alpha toxin low dose [40 µg/kg]; (4) alpha toxin high dose [80 µg/kg]; and, (5) NaCl 0.9% as control group. Gas was sampled from the expiratory line of the ventilator every 20 min and analyzed with IMS combined with a multi-capillary column. VOCs were identified by comparison with an established database. Survival analysis was performed by log-rank test, other analyses by one-way or paired ANOVA-tests and post-hoc analysis according to Holm-Sidak. Rats given NaCl and low-dose alpha toxin survived 24 h. The median survival time in alpha toxin high-dose group was 23 (95%-confidence interval (CI): 21, 24) h. In contrast, the median survival time in rats given high-dose lipopolysaccharide was 12 (95% CI: 9, 14) and only 13 (95% CI: 10, 16) h in those given high-dose lipopolysaccharide. 73 different VOCs were detected, of which 35 were observed only in the rats, 38 could be found both in the blank measurements of ventilator air and in the exhaled air of the rats. Forty-nine of the VOCs were identifiable from a registry of compounds. Exhaled volatile compounds were comparable in each group before injection of lipopolysaccharide and alpha toxin. In the LPS groups, 1-pentanol increased and 2-propanol decreased. After alpha toxin treatment, 1-butanol and 1-pentanol increased whereas butanal and isopropylamine decreased. Induction of a non-infectious systemic inflammation (niSI) by lipopolysaccharide and alpha toxin changes VOCs in exhaled breath. Exhalome analysis may help identify niSI.
Collapse
Affiliation(s)
- Dominik Lorenz
- CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Building 57, 66421, Homburg, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Early Systemic Inflammatory Response Syndrome Duration Predicts Infected Pancreatic Necrosis. J Gastrointest Surg 2020; 24:590-597. [PMID: 30891659 DOI: 10.1007/s11605-019-04149-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 02/01/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND PURPOSE Systemic inflammatory response syndrome (SIRS) was considered to play an important role in the progress of acute pancreatitis, but its specific relation with infected pancreatic necrosis remains largely unclear. We aimed to investigate the correlation between SIRS duration and infected pancreatic necrosis, and its application in prediction of infected pancreatic necrosis. METHODS A prospective observational cohort study of 2130 patients with acute pancreatitis from 2012 to 2017. The SIRS duration at the first week was registered daily, and demographic, radiology, and all clinical laboratory data were prospectively collected and retrospectively reviewed. RESULTS A significant upward tendency of infected pancreatic necrosis incidence was observed with increased SIRS duration. In multivariate logistic regression, SIRS duration (odds ratio, 1.305; 95% CI, 1.161-1.468) was independently associated with infected pancreatic necrosis. ROC analysis demonstrated that the areas under curves of SIRS duration for predicting persistent multi-organ failure, pancreatic infection, and mortality were 0.97 (95% CI, 0.96-0.98), 0.92 (95% CI, 0.91-0.94), and 0.86 (95% CI, 0.83-0.90), respectively, which were comparable to, or even greater than, the area under curves of APACHE II and CT severity index scores. CONCLUSIONS Early SIRS duration was strongly associated with infected pancreatic necrosis and could serve as an easy bedside indicator to predict pancreatic infection.
Collapse
|
|
26
|
Charalabopoulos A, Davakis S, Lambropoulou M, Papalois A, Simopoulos C, Tsaroucha A. Apigenin Exerts Anti-inflammatory Effects in an Experimental Model of Acute Pancreatitis by Down-regulating TNF-α. In Vivo 2019; 33:1133-1141. [PMID: 31280202 DOI: 10.21873/invivo.11583] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Revised: 06/06/2019] [Accepted: 06/10/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND/AIM This study investigated the anti-inflammatory effect of apigenin in an experimental model of acute pancreatitis. Inflammatory response was reflected by tissue expression of the cytokine TNF-α coupled with histological examination. MATERIALS AND METHODS Wistar rats were divided into three groups: Sham-group animals underwent laparotomy only, without any other interventions. Control-group animals underwent laparotomy and bilio-pancreatic duct ligation to induce pancreatitis without apigenin administration. Apigenin group animals were further treated with apigenin. Euthanasia was performed at 6, 12, 24, 48 and 72 h post-operatively. RESULTS Over-expression of TNF-α in relation to postoperative time was observed in the control group (p<0.001). In the apigenin group, under-expression of TNF-α in relation to postoperative time was observed (p<0.013). At 72 h, apigenin reduced pancreatic TNF-α expression and prevented pancreatic necrosis. CONCLUSION Apigenin slows progression and reduces severity of acute pancreatitis. Apigenin may serve as an adjunct to a more successful therapeutic strategy in acute pancreatitis.
Collapse
Affiliation(s)
- Alexandros Charalabopoulos
- Department of Upper Gastrointestinal and General Surgery, Broomfield Hospital, Mid Essex Hospital Services NHS Trust, Essex, U.K.,Experimental-Research Center, ELPEN Pharmaceuticals, Athens, Greece
| | - Spyridon Davakis
- Department of Upper Gastrointestinal and General Surgery, Broomfield Hospital, Mid Essex Hospital Services NHS Trust, Essex, U.K. .,First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Lambropoulou
- Department of Histopathology, Faculty of Medicine, Democritus University of Thrace, Alexandroupoli, Greece
| | | | - Constantinos Simopoulos
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, Alexandroupoli, Greece
| | - Alexandra Tsaroucha
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, Alexandroupoli, Greece
| |
Collapse
|
|
27
|
Su YR, Hong YP, Mei FC, Wang CY, Li M, Zhou Y, Zhao KL, Yu J, Wang WX. High-Fat Diet Aggravates the Intestinal Barrier Injury via TLR4-RIP3 Pathway in a Rat Model of Severe Acute Pancreatitis. Mediators Inflamm 2019; 2019:2512687. [PMID: 31933540 PMCID: PMC6942875 DOI: 10.1155/2019/2512687] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 11/25/2019] [Accepted: 12/03/2019] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE For patients with severe acute pancreatitis (SAP), a high body mass index (BMI) increases the possibility of infection derived from the intestine. In this study, we evaluate whether TAK242 can alleviate severe acute pancreatitis-associated injury of intestinal barrier in high-fat diet-fed rats. METHODS A SAP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty Sprague-Dawley (SD) adult rats were randomly divided into five groups: standard rat chow (SRC) normal (SN), SRC SAP (SAP), high-fat diet normal (HN), HFD SAP (HSAP), and TLR4 inhibitor pretreatment HFD SAP (HAPT) groups. Intraperitoneal injection of 3 mg/kg TAK242 was administered 30 minutes before SAP model establishment in the HAPT group. Rats were sacrificed 12 hours after SAP modeling, followed by blood and pancreatic and distal ileum tissue collection for further analyses. Changes in the pathology responses of the rats in each group were assessed. RESULT Analyses of serum amylase, lipase, cholesterol, triglyceride, IL-1β, IL-6, DAO, and serum endotoxin as well as tight junction protein expression including zonula occluden-1 and occludin indicated that high-fat diet aggravated SAP-induced intestinal barrier injury via increasing inflammatory response. In addition, the level of necroptosis was significantly higher in the SAP group compared with the SN group while the HSAP group exhibited more necroptosis compared with the SAP group, indicating the important role of necroptosis in pancreatitis-associated gut injury and illustrating that high-fat diet aggravated necroptosis of the ileum. Pretreatment with TLR4 inhibitor significantly alleviated inflammatory response and reduced necroptosis and level of oxidative stress while improving intestinal barrier function. CONCLUSION High-fat diet aggravated SAP-induced intestinal barrier injury via inflammatory reactions, necroptosis, and oxidative stress. Inhibition of TLR4 by TAK242 reduced inflammation, alleviated necroptosis, and lowered the level of oxidative stress and then protected the intestinal barrier dysfunction from SAP in high-fat diet-fed rats.
Collapse
Affiliation(s)
- Ying-ru Su
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
- Hubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, China
| | - Yu-pu Hong
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Fang-chao Mei
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chen-yang Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Man Li
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yu Zhou
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Kai-liang Zhao
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jia Yu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Wei-xing Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| |
Collapse
|
|
28
|
Abstract
The incidence of acute pancreatitis continues to increase worldwide, and it is one of the most common gastrointestinal causes for hospital admission in the USA. In the past decade, substantial advancements have been made in our understanding of the pathophysiological mechanisms of acute pancreatitis. Studies have elucidated mechanisms of calcium-mediated acinar cell injury and death and the importance of store-operated calcium entry channels and mitochondrial permeability transition pores. The cytoprotective role of the unfolded protein response and autophagy in preventing sustained endoplasmic reticulum stress, apoptosis and necrosis has also been characterized, as has the central role of unsaturated fatty acids in causing pancreatic organ failure. Characterization of these pathways has led to the identification of potential molecular targets for future therapeutic trials. At the patient level, two classification systems have been developed to classify the severity of acute pancreatitis into prognostically meaningful groups, and several landmark clinical trials have informed management strategies in areas of nutritional support and interventions for infected pancreatic necrosis that have resulted in important changes to acute pancreatitis management paradigms. In this Review, we provide a summary of recent advances in acute pancreatitis with a special emphasis on pathophysiological mechanisms and clinical management of the disorder.
Collapse
|
|
29
|
Wang F, Wen Q, Zhang S, Fu Z, Liu F, Cui J, Liu J, Tian H. Sustained bile drainage decreases the organs injuries via inflammation-associated factors modulation in a severe acute pancreatitis rat model. Exp Ther Med 2019; 17:4628-4634. [PMID: 31086593 PMCID: PMC6489021 DOI: 10.3892/etm.2019.7478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 03/07/2019] [Indexed: 11/06/2022] Open
Abstract
The timely and effective treatment for severe acute pancreatitis (SAP) is favorable to prognosis. Decompression of the bile duct might be a feasible way to decrease the progression of SAP. The present study investigated the effects of sustained bile external drainage on organs injury caused by SAP in Sprague-Dawley (SD) rats and the mechanisms involved. A total of 72 female SD rats weighting 190-230 g were randomly divided into four groups (n=18): Sham operation group (SOG), SOG + bile drainage group (BDG), SAP group, and SAP + BDG. Sodium taurocholate solution (4%; 1 mg/kg body weight) was used to set up SAP model via injection of retrograde puncture of biliopancreatic duct through the duodenum. A cannula was inserted into the bile duct and fixed externally to establish BDG model. At each time points (t=3, 6, 12; n=6), tissues from the liver, lung, and pancreas, and blood samples were collected. Serum amylase (AMY) was analyzed in all the samples. The levels of tumor necrosis factor-α (TNF-α), heme oxygenase-1 (HO-1), interleukin-10 (IL-10) and high mobility group box 1 (HMGB1) were detected by ELISA. Hematoxylin-eosin staining was performed to observe the histopathological changes, and nuclear transcription factor (NF)-κB-p65 levels in the pancreas were analyzed by western blotting. The data indicated that BDG alleviated the SAP progression and multiple organs injuries. Meanwhile, the histopathological changes of the pancreas, liver, and lungs were improved by BDG. BDG decreased the pathological scores of pancreas significantly (P<0.05). The levels of AMY, TNF-α, HMGB1, and NF-κB-p65 were significantly downregulated by BDG (P<0.05), while the level of HO-1 was upregulated and IL-10 was unchanged. In summary, BDG may attenuate the multiple organs injuries caused by SAP via downregulation of TNF-α, HMGB1, NF-κB-p65 and upregulation of HO-1.
Collapse
Affiliation(s)
- Fuhai Wang
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Qingbin Wen
- Department of Surgery, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China
| | - Sai Zhang
- Department of Surgery, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China
| | - Zhen Fu
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Feng Liu
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Jing Cui
- Department of Pathology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Ju Liu
- Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Hu Tian
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| |
Collapse
|
|
30
|
Serum apolipoprotein B-to-apolipoprotein A1 ratio is independently associated with disease severity in patients with acute pancreatitis. Sci Rep 2019; 9:7764. [PMID: 31123322 PMCID: PMC6533319 DOI: 10.1038/s41598-019-44244-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 05/13/2019] [Indexed: 12/18/2022] Open
Abstract
Early identification of severe acute pancreatitis (SAP) is critical for clinical decision-making. The apolipoprotein B-to-apolipoprotein A1 ratio (ApoB/A1 ratio) reflects the balance between pro-inflammation and anti-inflammation in vivo. This study investigated the association between serum ApoB/A1 ratio at admission and acute pancreatitis (AP) severity. A total of 375 patients with first attack of AP were retrospectively recruited from January 2014 to December 2017. The severity of AP was assessed at admission based on the 2012 revised Atlanta Classification. Serum lipids levels were tested on the first 24 h of hospitalization, of which the correlations with clinical features or scoring systems were also measured. The ApoB/A1 ratio markedly increased across disease severity of AP. The ApoB/A1 ratio, expressed as both quartile and continuous variables, was significantly associated with a high risk of SAP, even after adjustment for other conventional SAP risk factors. The ApoB/A1 ratio positively correlated with the revised 2012 Atlanta Classification, Ranson score, Bedside Index for Severity in AP score, Modified Computed Tomography Severity Index score, and Acute Physiology and Chronic Health Evaluation II score for AP severity. The optimal cut-off value of ApoB/A1 ratio for detecting SAP was 0.88, with a sensitivity of 83.08% and a specificity of 69.03%. Serum ApoB/A1 ratio at admission is closely correlated with disease severity in patients with AP and can serve as a reliable indicator for SAP in clinical setting.
Collapse
|
|
31
|
Does Etiology of Pancreatitis Matter? Differences in Outcomes Among Patients With Post-Endoscopic Retrograde Cholangiopancreatography, Acute Biliary, and Alcoholic Pancreatitis. Pancreas 2019; 48:574-578. [PMID: 30946237 DOI: 10.1097/mpa.0000000000001283] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES We compared outcomes of acute alcoholic pancreatitis (AAP), acute biliary pancreatitis (ABP), and post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). METHODS This was a retrospective cohort study conducted at a tertiary care center between June 2007 and June 2012. RESULTS A total of 300 (68%) patients were diagnosed with AAP, 88 (20%) with ABP, and 55 (12%) with PEP. Longer length of hospital stay (LOHS) was more common in ABP (23%) as compared with AAP (10%) and PEP (7%, P = 0.025). Pseudocyst (P = 0.048), organ failure (OF) (P = 0.01), need for interventions (P ≤ 0.001), and mortality (P = 0.002) occurred more in ABP as compared with other groups. Systemic inflammatory response syndrome was associated with LOHS of more than 10 days (P = 0.01) and multi-OF (P = 0.05). Chronic pancreatitis was associated more with pseudocyst (P < 0.001) and mortality (P = 0.03). Serum urea nitrogen of greater than 25 g/dL predicted LOHS of more than 10 days (P = 0.02), OF (P < 0.001), multi-OF (P < 0.001), and persistent OF (P < 0.001). CONCLUSIONS Acute biliary pancreatitis is a more severe disease compared with PEP and AAP. Chronic pancreatitis, systemic inflammatory response syndrome, and high serum urea nitrogen are important predictors of morbidity.
Collapse
|
|
32
|
Zhang R, Shi J, Zhang R, Ni J, Habtezion A, Wang X, Hu G, Xue J. Expanded CD14hiCD16−Immunosuppressive Monocytes Predict Disease Severity in Patients with Acute Pancreatitis. THE JOURNAL OF IMMUNOLOGY 2019; 202:2578-2584. [DOI: 10.4049/jimmunol.1801194] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 02/25/2019] [Indexed: 12/16/2022]
|
|
33
|
Talukdar R. Progression of recurrent acute to chronic pancreatitis: More questions than answers! Indian J Gastroenterol 2018; 37:77-78. [PMID: 29552743 DOI: 10.1007/s12664-018-0839-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Rupjyoti Talukdar
- Pancreas Research Group, Asian Healthcare Foundation/Wellcome DBT Labs, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India.
| |
Collapse
|