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The Turkish Journal of Gastroenterology... Aug 2023Acute pancreatitis, a prevalent illness with devastating consequences, poses a grave threat to those affected. There has been a steady increase in the occurrence of...
Acute pancreatitis, a prevalent illness with devastating consequences, poses a grave threat to those affected. There has been a steady increase in the occurrence of acute pancreatitis at about 3% per year from 1961 to 2016. There are 3 main guidelines on acute pancreatitis, including the American College of Gastroenterology, the International Association of Pancreatology/American Pancreatic Association guideline in 2013, and the American Gastroenterological Association guideline in 2018. However, several milestone studies have been published since then. We hereby reviewed the current acute pancreatitis guidelines with an update on clinical practicechanging literature. The aggressive or moderate fluid resuscitation in acute pancreatitis (WATERFALL) trial recommended fluid resuscitation with lactated Ringer's solution at a moderate aggressive rate. All guidelines did not recommend prophylactic antibiotics use. Early enteral feeding reduces morbidity. A clear liquid diet is no longer recommended. Nutrition with nasogastric or nasojejunal feeding does not have a difference. The upcoming high vs. low-energy administration in the early phase of acute pancreatitis (GOULASH) trial will provide more information on the impact of calorie intake. Pain management should be individualized based on the degree of pain and severity of pancreatitis. In patients with moderate to severe and severe acute pancreatitis, a step-down approach with epidural analgesia can be considered for moderate to severe pain. The management of acute pancreatitis has evolved. New research on the impact of electrolytes, pharmacologic agents, the role of anticoagulants, and nutrition support will provide scientific and clinical evidence to improve patient care and decrease morbidity and mortality.
Topics: Humans; Pancreatitis; Acute Disease; Enteral Nutrition; Nutritional Support; Pancreas
PubMed: 37404118
DOI: 10.5152/tjg.2023.23175 -
World Journal of Gastroenterology Oct 2023Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by the severity of the disease.... (Review)
Review
Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by the severity of the disease. Diagnosis, severity prediction, and prognosis assessment of AP typically involve the use of imaging technologies, such as computed tomography, magnetic resonance imaging, and ultrasound, and scoring systems, including Ranson, Acute Physiology and Chronic Health Evaluation II, and Bedside Index for Severity in AP scores. Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity, while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications. Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild, moderate, or severe categories, guiding treatment decisions, such as intensive care unit admission, early enteral feeding, and antibiotic use. Despite the central role of imaging technologies and scoring systems in AP management, these methods have limitations in terms of accuracy, reproducibility, practicality and economics. Recent advancements of artificial intelligence (AI) provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data. AI algorithms can analyze large amounts of clinical and imaging data, identify scoring system patterns, and predict the clinical course of disease. AI-based models have shown promising results in predicting the severity and mortality of AP, but further validation and standardization are required before widespread clinical application. In addition, understanding the correlation between these three technologies will aid in developing new methods that can accurately, sensitively, and specifically be used in the diagnosis, severity prediction, and prognosis assessment of AP through complementary advantages.
Topics: Humans; Pancreatitis; Severity of Illness Index; Artificial Intelligence; Acute Disease; Reproducibility of Results; Prognosis; Retrospective Studies; Predictive Value of Tests
PubMed: 37899784
DOI: 10.3748/wjg.v29.i37.5268 -
Clinical and Translational... Aug 2023Drug induced acute pancreatitis is a difficult diagnosis for clinicians. We previously published an "Evidence-Based Classification System" on Drug-Induced Acute...
INTRODUCTION
Drug induced acute pancreatitis is a difficult diagnosis for clinicians. We previously published an "Evidence-Based Classification System" on Drug-Induced Acute Pancreatitis widely used by clinicians to assist in the identification of drugs. Unfortunately, this prior analysis based only on published case reports has been misunderstood. The prior review did not include studies with higher evidentiary value, such as randomized trials, case-control studies, and/or pharmacoepidemiologic studies. The use of the prior classification system has led to many patients being inappropriately labeled as having drug-induced acute pancreatitis. We now propose a "Revised" Evidence- Based Classification System for the purpose of determining which drugs cause acute pancreatitis based on the Grading of Recommendations, Development, and Evaluation criteria.
METHODS
A search of the English Language literature was performed to identify all case reports with medication and/or drug induced acute pancreatitis. We divided the drugs implicated as causing acute pancreatitis into four groups based on the quality of evidence as defined by GRADE quality parameters.
RESULTS
Although 141 drugs were identified in the literature as causing acute pancreatitis, only 106 drugs published in the literature as causing acute pancreatitis were high quality case reports. Only 3 drugs had evidence as causing acute pancreatitis from randomized controlled clinical trials, including 6-mercaptopurine and azathioprine.
DISCUSSION
The vast majority of drugs implicated as causing acute pancreatitis in the literature have low or very low quality of evidence supporting those claims.
Topics: Humans; Pancreatitis; Acute Disease; Case-Control Studies
PubMed: 37440319
DOI: 10.14309/ctg.0000000000000621 -
Clinical Nutrition (Edinburgh, Scotland) Feb 2024Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and...
Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20 % of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered.
Topics: Humans; Acute Disease; Enteral Nutrition; Pancreatitis, Chronic; Malnutrition
PubMed: 38169174
DOI: 10.1016/j.clnu.2023.12.019 -
Gut Feb 2024Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP...
OBJECTIVE
Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission.
DESIGN
Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated.
RESULTS
After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP.
CONCLUSIONS
The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts.
TRIAL REGISTRATION NUMBER
NCT04777812.
Topics: Humans; Pancreatitis; Gastrointestinal Microbiome; Acute Disease; RNA, Ribosomal, 16S; Severity of Illness Index
PubMed: 38129103
DOI: 10.1136/gutjnl-2023-330987 -
Cell Death & Disease Oct 2023Acute pancreatitis (AP) is a common emergency of the digestive system and serious cases can develop into severe acute pancreatitis (SAP), which ortality rates up to 30%....
Acute pancreatitis (AP) is a common emergency of the digestive system and serious cases can develop into severe acute pancreatitis (SAP), which ortality rates up to 30%. Sirtuin4 (SIRT4) is a member of the sirtuin family, and plays a key role in inflammation and oxidative stress. However, the potential role of SIRT4 in SAP has yet to be elucidated. In the present study, we found that the expression level of SIRT4 in human AP was downregulated by screening a public database, suggesting that SIRT4 may play a role in AP. Subsequently, we used L-arginine (L-Arg) to induce SAP in SIRT4 knockout (SIRT4_KO) and SIRT4 overexpression (AAV_SIRT4) mice. The results showed that the pancreatic tissue injury and related lung and kidney injury were serious in SIRT4_KO mice after SAP induction, but were significantly reduced in AAV_SIRT4 mice. More importantly, we found that the levels of antioxidant factors GSH and SOD were decreased in SIRT4_KO mice, and the production of oxidative products and lipid peroxidation markers was increased, suggesting that SIRT4 was involved in inflammation and oxidative stress during SAP. Further studies showed that the absence or overexpression of SIRT4 affected the expression level of Hypoxia-inducible factor-1α (HIF-1α) after SAP induction, and regulated the expression of ferroptosis related proteins by mediating HIF-1α/HO-1 pathway. Collectively, our study revealed that SIRT4 plays a protective role in SAP by regulating the HIF-1α/HO-1 pathway to inhibit ferroptosis.
Topics: Animals; Humans; Mice; Acute Disease; Ferroptosis; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Pancreatitis
PubMed: 37865653
DOI: 10.1038/s41419-023-06216-x -
Gastroenterology Jun 2024Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing studies of the pancreas...
BACKGROUND & AIMS
Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing studies of the pancreas underrepresent acinar cells relative to histological expectations, and a robust approach to capture pancreatic cell responses in disease states is needed. We sought to innovate a method that overcomes these challenges to accelerate study of the pancreas in health and disease.
METHODS
We leverage FixNCut, a single-cell RNA-sequencing approach in which tissue is reversibly fixed with dithiobis(succinimidyl propionate) before dissociation and single-cell preparation. We apply FixNCut to an established mouse model of acute pancreatitis, validate findings using GeoMx whole transcriptome atlas profiling, and integrate our data with prior studies to compare our method in both mouse and human pancreas datasets.
RESULTS
FixNCut achieves unprecedented definition of challenging pancreatic cells, including acinar and immune populations in homeostasis and acute pancreatitis, and identifies changes in all major cell types during injury and recovery. We define the acinar transcriptome during homeostasis and acinar-to-ductal metaplasia and establish a unique gene set to measure deviation from normal acinar identity. We characterize pancreatic immune cells, and analysis of T-cell subsets reveals a polarization of the homeostatic pancreas toward type-2 immunity. We report immune responses during acute pancreatitis and recovery, including early neutrophil infiltration, expansion of dendritic cell subsets, and a substantial shift in the transcriptome of macrophages due to both resident macrophage activation and monocyte infiltration.
CONCLUSIONS
FixNCut preserves pancreatic transcriptomes to uncover novel cell states during homeostasis and following pancreatitis, establishing a broadly applicable approach and reference atlas for study of pancreas biology and disease.
Topics: Animals; Pancreatitis; Homeostasis; Transcriptome; Single-Cell Analysis; Humans; Acinar Cells; Mice; Disease Models, Animal; Pancreas; Gene Expression Profiling; RNA-Seq; Acute Disease; Pancreas, Exocrine; Macrophages; Metaplasia; Mice, Inbred C57BL
PubMed: 38325760
DOI: 10.1053/j.gastro.2024.01.043 -
Microbiology Spectrum Aug 2023The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung...
Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway.
The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased / ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, , Enterobacter, , ) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (, , , , ). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.
Topics: Mice; Animals; Pancreatitis; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; AMP-Activated Protein Kinases; Gastrointestinal Microbiome; Acute Disease; Prospective Studies; Acute Lung Injury; Fatty Acids, Volatile
PubMed: 37338348
DOI: 10.1128/spectrum.03664-22 -
Renal Failure Dec 2023Acute pancreatitis (AP) is associated with a high incidence of acute kidney injury (AKI). This study aimed to develop a nomogram for predicting the early onset of AKI in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Acute pancreatitis (AP) is associated with a high incidence of acute kidney injury (AKI). This study aimed to develop a nomogram for predicting the early onset of AKI in AP patients admitted to the intensive care unit.
METHOD
Clinical data for 799 patients diagnosed with AP were extracted from the Medical Information Mart for Intensive Care IV database. Eligible AP patients were randomly divided into training and validation cohorts. The independent prognostic factors for the early development of AKI in AP patients were determined using the all-subsets regression method and multivariate logistic regression. A nomogram was constructed for predicting the early occurrence of AKI in AP patients. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA).
RESULTS
Seven independent prognostic factors were identified as predictive factors for early onset AKI in AP patients. The AUC of the nomogram in the training and validation cohorts were 0.795 (95% CI, 0.758-0.832) and 0.772 (95% CI, 0.711-0.832), respectively. The AUC of the nomogram was higher compared with that of the BISAP, Ranson, APACHE II scores. Further, the calibration curve revealed that the predicted outcome was in agreement with the actual observations. Finally, the DCA curves showed that the nomogram had a good clinical applicability value.
CONCLUSION
The constructed nomogram showed a good predictive ability for the early occurrence of AKI in AP patients.
Topics: Humans; Acute Kidney Injury; Databases, Factual; Pancreatitis; Retrospective Studies; Models, Statistical
PubMed: 36999227
DOI: 10.1080/0886022X.2023.2194436 -
Medicine Nov 2023Acute pancreatitis (AP) is one of the most common gastrointestinal diseases, and it is divided into 3 types according to its severity:mild acute pancreatitis, moderately... (Review)
Review
Acute pancreatitis (AP) is one of the most common gastrointestinal diseases, and it is divided into 3 types according to its severity:mild acute pancreatitis, moderately severe acute pancreatitis, and severe acute pancreatitis. The mortality in severe acute pancreatitis is approximately 15% to 30% due to multiorgan dysfunction and the lack of specific treatment. Interleukin-22 (IL-22) is a member of the Interleukin-10 family, and it can activate several downstream signaling pathways by binding to its receptor complex, thus it is involved in cell differentiation, proliferation, and apoptosis. Some studies have reported the elevated level of IL-22 in patients with AP, which suggests IL-22 may be involved in the pathogenesis of AP. And many studies have shown that IL-22 had a protective effect against AP. This article reviews the characteristics and mechanism of IL-22 and its role in AP to provide insight into the treatment of AP.
Topics: Humans; Pancreatitis; Acute Disease; Interleukin-6; Interleukins; Severity of Illness Index; Interleukin-22
PubMed: 37933011
DOI: 10.1097/MD.0000000000035695