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Biomedicine & Pharmacotherapy =... Dec 2020Severe acute pancreatitis (SAP), a serious inflammatory disease of the pancreas, can easily lead to systemic inflammatory response syndrome (SIRS) and multiple organ... (Review)
Review
Severe acute pancreatitis (SAP), a serious inflammatory disease of the pancreas, can easily lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS). Acute lung injury (ALI) is one of the most serious complications of SAP. However, the specific pathogenesis of SAP-associated ALI is not fully understood. Crosstalk and multi-mechanisms involving pancreatic necrosis, bacteremia, intestinal barrier failure, activation of inflammatory cascades and diffuse alveolar damage is the main reason for the unclear pathological mechanism of SAP-associated ALI. According to previous research on SAP-associated ALI in our laboratory and theories put forward by other scholars, we propose that the complex pattern of SAP-associated ALI is based on the "pancreas-intestine-inflammation/endotoxin-lung (P-I-I/E-L) pathway". In this review, we mainly concentrated on the specific details of the "P-I-I/E-L pathway" and the potential treatments or preventive measures for SAP-associated ALI.
Topics: Acute Lung Injury; Animals; Endotoxins; Humans; Intestines; Multiple Organ Failure; Pancreatitis; Pancreatitis, Acute Necrotizing; Systemic Inflammatory Response Syndrome
PubMed: 33011613
DOI: 10.1016/j.biopha.2020.110770 -
Medicine Apr 2019Severity stratification and prognostic prediction at early stage is crucial for reducing the rates of mortality of patients with acute pancreatitis (AP). We aim to...
Severity stratification and prognostic prediction at early stage is crucial for reducing the rates of mortality of patients with acute pancreatitis (AP). We aim to investigate the predicting performance of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red-cell distribution width (RDW) combined with severity scores (sequential organ failure assessment [SOFA], bed-side index for severity of AP [BISAP], Ranson criteria, and acute physiology and chronic health evaluation II [APACHE II]) for severe AP (SAP) and mortality.A total of 406 patients diagnosed with AP admitted in a tertiary teaching hospital were enrolled. Demographic information and clinical parameters were retrospectively collected and analyzed. NLR, PLR, RDW, blood urea nitrogen (BUN), and AP severity scores (SOFA, BISAP, Ranson, and APACHE II) were compared between different severity groups and the survival and death group. Receiver-operating characteristic (ROC) curves for SAP and 28-day mortality were calculated for each predictor using cut-off values. Area under the curve (AUC) analysis and logistic regression models were performed to compare the performance of laboratory biomarkers and severity scores.Our results showed that NLR, PLR, RDW, glucose, and BUN level of the SAP group were significantly increased compared to the mild acute pancreatitis (MAP) group on admission (P < .001). The severity of AP increased as the NLR, SOFA, BISAP, and Ranson increased (P < .01). The AUC values of NLR, PLR, RDW, BUN, SOFA, BISAP, Ranson, and APACHE II to predict SAP were 0.722, 0.621, 0.787, 0.677, 0.806, 0.841, 0.806, and 0.752, respectively, while their AUC values to predict 28-day mortality were 0.851, 0.693, 0.885, 0.765, 0.968, 0.929, 0.812, and 0.867, respectively. BISAP achieved the highest AUC, sensitivity and NPV in predicting SAP, while SOFA is the most superior in predicting mortality. The combination of BISAP + RDW achieved the highest AUC (0.872) in predicting SAP and the combination of SOFA + RDW achieved the highest AUC (0.976) in predicting mortality. RDW (OR = 1.739), SOFA (OR = 1.554), BISAP (OR = 2.145), and Ranson (OR = 1.434) were all independent risk factors for predicting SAP, while RDW (OR = 7.361) and hematocrit (OR = 0.329) were independent risk factors for predicting mortality by logistic regression model.NLR, PLR, RDW, and BUN indicated good predictive value for SAP and mortality, while RDW had the highest discriminatory capacity. RDW is a convenient and reliable indicator for prediction not only SAP, but also mortality.
Topics: APACHE; Acute Disease; Adult; Aged; Female; Humans; Male; Middle Aged; Pancreatitis; Prognosis; Retrospective Studies; Severity of Illness Index
PubMed: 31008971
DOI: 10.1097/MD.0000000000015275 -
PloS One 2020A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with...
OBJECTIVE
A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations.
METHODS
A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency.
RESULTS
Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis.
DISCUSSION
Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations.
REGISTRATION
CRD42017060473.
Topics: Acute Disease; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pancreatitis; Pharmaceutical Preparations
PubMed: 32302358
DOI: 10.1371/journal.pone.0231883 -
EBioMedicine Aug 2020Impaired or hyperactive pancreas regeneration after injury would cause exocrine insufficiency or recurrent / chronic pancreatitis and potentially carcinogenesis....
BACKGROUND
Impaired or hyperactive pancreas regeneration after injury would cause exocrine insufficiency or recurrent / chronic pancreatitis and potentially carcinogenesis. Macrophages are the most abundant immune cells in the regenerative pancreas, however their phenotype and role remain poorly defined.
METHOD
Using caerulein-induced acute pancreatitis (AP) model, we examined the dynamic landscape of pancreatic macrophages throughout the acute inflammation to regeneration phases by flow cytometric and RNA-seq analyses. Liposome depletion of macrophages, Il4ra mice as well as inhibitors were used to elucidate the role and regulatory mechanism of macrophages during pancreatic regeneration.
FINDINGS
We found that M1 macrophages dominated in the pro-inflammatory phase of AP, while M2-like macrophages dominated during pancreas repair/regeneration. Depletion of macrophages at early or late regenerative stage dramatically blocked the acinar-ductal metaplasia (ADM) or delayed inflammation resolution, respectively. Moreover, alternative activation of macrophages was partially dependent on IL-4RA signaling, and ECM/AKT activation in pancreatic macrophages facilitated inflammation resolution during tissue regeneration.
INTERPRETATION
Our findings illustrate a dynamic phenotype and function of macrophages during AP repair/regeneration, helping us better understand the mechanism of pancreatic regeneration and providing clues for novel therapeutic strategy.
Topics: Animals; Cell Polarity; Ceruletide; Disease Models, Animal; Gene Expression Profiling; Liposomes; Liver Regeneration; Macrophages; Mice; Pancreatitis; Phenotype; Receptors, Cell Surface; Sequence Analysis, RNA; Wound Healing
PubMed: 32739869
DOI: 10.1016/j.ebiom.2020.102920 -
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 -
Ugeskrift For Laeger Feb 2020Hereditary pancreatitis (HP) is an autosomal dominant disease with 80% penetrance. HP is characterised by the debut of recurrent acute pancreatitis episodes during... (Review)
Review
Hereditary pancreatitis (HP) is an autosomal dominant disease with 80% penetrance. HP is characterised by the debut of recurrent acute pancreatitis episodes during childhood with gradual progression to chronic pancreatitis. Patients with phenotypic HP have a significantly increased lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC). Patients with HP represent a rare but important group of high-risk individuals in need of early diagnosis and screening for potential PDAC. The aim of this review is to provide an overview of the epidemiology, genetics and clinical aspects of HP.
Topics: Acute Disease; Genetic Predisposition to Disease; Humans; Mutation; Pancreatic Neoplasms; Pancreatitis; Pancreatitis, Chronic
PubMed: 32138812
DOI: No ID Found -
World Journal of Gastroenterology Jun 2020With over 100000 hospital admissions per annum, acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has... (Review)
Review
With over 100000 hospital admissions per annum, acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has far-reaching impact well beyond. It has become increasingly recognized that drug-induced pancreatitis (DIP), despite accounting for less than 3% of all cases, represents an important and growing though often inconspicuous cause of acute pancreatitis. Nevertheless, knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents, especially for non-prescription medications. Indeed, the majority of available data is derived from case reports, case series, or case control studies. Furthermore, the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established (< 10% of cases). Several classification systems have been proposed, but no single system has been widely adopted, and periodic updates are required in light of ongoing pharmacologic expansion. Moreover, infrequently prescribed medications or those available over-the-counter (including herbal and other alternative remedies) are often overlooked as a potential culprit of acute pancreatitis. Herein, we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity. We believe this manuscript will aid in increasing both primary and secondary prevention of DIP, thus ultimately facilitating more expedient diagnosis and a decrease in DIP-related morbidity.
Topics: Acute Disease; Case-Control Studies; Hospitalization; Humans; Pancreatitis; Pharmaceutical Preparations; United States
PubMed: 32587438
DOI: 10.3748/wjg.v26.i22.2902 -
Journal of Gastroenterology Jul 2016Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate... (Review)
Review
BACKGROUND
Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases.
METHODS
This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models.
RESULTS
Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis.
CONCLUSIONS
These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder.
Topics: Acinar Cells; Humans; Pancreatitis; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 26879861
DOI: 10.1007/s00535-016-1175-3 -
JPMA. the Journal of the Pakistan... May 2024Acute pancreatitis is a common cause of acute abdominal pain and can range from mild oedema to severe necrosis of the pancreas. It has a significant impact on morbidity,... (Review)
Review
Acute pancreatitis is a common cause of acute abdominal pain and can range from mild oedema to severe necrosis of the pancreas. It has a significant impact on morbidity, mortality and financial burden. The global prevalence of pancreatitis is substantial, with the highest rates observed in central and eastern Europe. Diagnosing acute pancreatitis involves considering clinical symptoms, elevated serum amylase and/or lipase levels, and characteristic imaging findings. The causes of acute pancreatitis include obstructive disorders, such as gallstones and biliary sludge, alcohol consumption, smoking, drug-induced pancreatitis, metabolic disorders, trauma, medical procedures, infections, vascular diseases and autoimmune pancreatitis. Appropriate management of acute pancreatitis involves determining the severity of the condition, providing supportive care, addressing the underlying cause, and preventing complications. Advances in classifying the severity of acute pancreatitis and implementing goal-directed therapy have contributed to a decrease in mortality rates. Understanding its prevalence, aetiology and management principles is crucial for clinicians to appropriately diagnose and manage patients with acute pancreatitis.
Topics: Humans; Pancreatitis; Acute Disease; Severity of Illness Index; Gallstones
PubMed: 38783446
DOI: 10.47391/JPMA.9280 -
World Journal of Gastroenterology Jul 2023Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out... (Review)
Review
Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.
Topics: Humans; Pancreatitis; Diabetes Mellitus, Type 2; Acute Disease; Risk Factors
PubMed: 37576704
DOI: 10.3748/wjg.v29.i28.4405