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Clinical Chemistry Oct 2023Triglycerides are a major source of energy, while high plasma triglycerides are a risk factor for various diseases and premature death. Severely elevated plasma...
BACKGROUND
Triglycerides are a major source of energy, while high plasma triglycerides are a risk factor for various diseases and premature death. Severely elevated plasma triglycerides are a well-established cause of acute pancreatitis with high mortality, likely due to the presence of elevated levels of chylomicrons and large very low-density lipoproteins in plasma. As markedly elevated levels of these very large lipoproteins are not generally found in mild to moderate hypertriglyceridemia, this was previously not regarded as a cause or marker of increased risk of acute pancreatitis. However, mild to moderate hypertriglyceridemia may identify individuals who at a later timepoint develop severe hypertriglyceridemia and acute pancreatitis.
CONTENT
We describe measurement of plasma triglycerides and studies on plasma triglycerides and risk of acute pancreatitis. Further, we summarize current European and American guidelines for the prevention of acute pancreatitis and, finally, the potential for future prevention of acute pancreatitis through lowering of plasma triglycerides.
SUMMARY
Recent observational and genetic studies indicate that mild to moderate hypertriglyceridemia is causally related to increased risk of acute pancreatitis, most likely as a marker of future severe hypertriglyceridemia. Current guidelines do not mention individuals with mild to moderate hypertriglyceridemia, even though newer evidence suggests an unmet medical need. Treatment could include plasma triglyceride-lowering therapy targeting the pathway for lipoprotein lipase as the main triglyceride degrading enzyme in plasma. Angiopoietin-like 3 and apolipoproteinC-III are inhibitors of lipoprotein lipase, and blocking of these 2 inhibitors is showing promising results in relation to marked triglyceride-lowering and could perhaps be used to prevent acute pancreatitis in the future.
Topics: Humans; Pancreatitis; Lipoprotein Lipase; Acute Disease; Hypertriglyceridemia; Triglycerides
PubMed: 37530032
DOI: 10.1093/clinchem/hvad094 -
Current Opinion in Pediatrics Oct 2023Pediatric acute pancreatitis is an infrequent but potentially serious condition in children. Most have mild cases with spontaneous resolution, but up to one-third of... (Review)
Review
PURPOSE OF REVIEW
Pediatric acute pancreatitis is an infrequent but potentially serious condition in children. Most have mild cases with spontaneous resolution, but up to one-third of patients can have moderate or severe disease or progress to recurrent or chronic pancreatitis.
RECENT FINDINGS
Significant advances have been made in the field of pediatric pancreatology with a recognition that pediatric acute pancreatitis can vary significantly from adult disease with different risk factors and outcomes. There is better understanding of appropriate management for pediatric pancreatitis as well as growing literature in complications of pancreatitis.
SUMMARY
The most common risk factors for pediatric acute pancreatitis include biliary disease, drug/toxin and idiopathic. Management involves adequate fluid resuscitation, early enteral nutrition and appropriate pain control. Systemic and local complications, including SIRS, necrosis and fluid collections, can occur in up to one-third of patients and care is largely supportive with a careful step-up approach to fluid collections and necrosis.
Topics: Adult; Humans; Child; Acute Disease; Risk Factors; Pancreatitis, Chronic; Necrosis
PubMed: 37594373
DOI: 10.1097/MOP.0000000000001285 -
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 -
Endocrine May 2024Although there is a definite correlation between the Metabolic Syndrome (MetS) and Acute Pancreatitis (AP), cause is yet unknown. The current work combined linkage...
BACKGROUND
Although there is a definite correlation between the Metabolic Syndrome (MetS) and Acute Pancreatitis (AP), cause is yet unknown. The current work combined linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) approaches to fill this important information gap.
METHODS
In this study, we harnessed the power of publicly available gene-wide association databases (GWAS) to explore the intricate relationship between MetS and its components with AP. The cornerstone of our analysis was the Inverse-Variance Weighted (IVW) method, serving as our primary analytical tool. In addition to IVW, we complemented our investigation with several other robust MR methods, including MR-Egger, Weighted Median, Maximum Likelihood, and MR-PRESSO. By employing this diverse set of analytical approaches, we sought to ensure the comprehensiveness and robustness of our findings.
RESULT
LDSC regression indicated a genetic correlation between MetS and AP. Univariate MR results indicated a genetic association between MetS (OR = 1.084; 95% CI, 1.005-1.170; P = 0.037), BMI (OR = 1.459; 95% CI, 1.325-1.606; P = 1.46E-14), WHR (OR = 1.189; 95% CI, 1.068-1.323; P = 1.56 E-03), TG (OR = 1.110; 95% CI, 1.001-1.231; P = 0.047), and FI (OR = 1.798; 95% CI, 1.245-2.595; P = 1.74E-03) were able to significantly increase the risk of AP. The results of multivariate MR analysis revealed that these causality associations still existed.
CONCLUSION
Our investigation has yielded compelling evidence that substantiates the presence of both a genetic correlation and a causal relationship between MetS and AP.
Topics: Humans; Metabolic Syndrome; Pancreatitis; Mendelian Randomization Analysis; Genome-Wide Association Study; Genetic Predisposition to Disease; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Acute Disease
PubMed: 37922090
DOI: 10.1007/s12020-023-03584-4 -
Frontiers in Immunology 2023Acute pancreatitis (AP) is one of the most common inflammatory diseases of the gastrointestinal tract and a steady rising diagnosis for inpatient hospitalization. About... (Review)
Review
Acute pancreatitis (AP) is one of the most common inflammatory diseases of the gastrointestinal tract and a steady rising diagnosis for inpatient hospitalization. About one in four patients, who experience an episode of AP, will develop chronic pancreatitis (CP) over time. While the initiating causes of pancreatitis can be complex, they consistently elicit an immune response that significantly determines the severity and course of the disease. Overall, AP is associated with a significant mortality rate of 1-5%, which is caused by either an excessive pro-inflammation, or a strong compensatory inhibition of bacterial defense mechanisms which lead to a severe necrotizing form of pancreatitis. At the time-point of hospitalization the already initiated immune response is the only promising common therapeutic target to treat or prevent a severe disease course. However, the complexity of the immune response requires fine-balanced therapeutic intervention which in addition is limited by the fact that a significant proportion of patients is in danger of development or progress to recurrent and chronic disease. Based on the recent literature we survey the disease-relevant immune mechanisms and evaluate appropriate and promising therapeutic targets for the treatment of acute and chronic pancreatitis.
Topics: Humans; Acute Disease; Pancreatitis, Chronic; Disease Progression
PubMed: 37881430
DOI: 10.3389/fimmu.2023.1279539 -
Pancreas Jul 2023Severe acute pancreatitis (SAP), pancreatic inflammation leading to multiorgan failure, is associated with high morbidity and mortality. There is a critical need to... (Review)
Review
OBJECTIVE
Severe acute pancreatitis (SAP), pancreatic inflammation leading to multiorgan failure, is associated with high morbidity and mortality. There is a critical need to identify novel therapeutic strategies to improve clinical outcomes for SAP patients.
MATERIALS AND METHODS
A comprehensive literature review was performed to identify current clinical strategies, known molecular pathophysiology, and potential therapeutic targets for SAP.
RESULTS
Current clinical approaches focus on determining which patients will likely develop SAP. However, therapeutic options are limited to supportive care and fluid resuscitation. The application of a novel 5-cytokine panel accurately predicting disease outcomes in SAP suggests that molecular approaches will improve impact of future clinical trials in AP.
CONCLUSIONS
Inflammatory outcomes in acute pancreatitis are driven by several unique molecular signals, which compound to promote both local and systemic inflammation. The identification of master cytokine regulators is critical to developing therapeutics, which reduce inflammation through several mechanisms.
Topics: Humans; Pancreatitis; Acute Disease; Inflammation; Fluid Therapy; Cytokines
PubMed: 38127317
DOI: 10.1097/MPA.0000000000002259 -
Pharmacology & Therapeutics Nov 2023Severe hypertriglyceridemia (sHTG), defined as a triglyceride (TG) concentration ≥ 500 mg/dL (≥ 5.7 mmol/L) is an important risk factor for acute pancreatitis.... (Review)
Review
Severe hypertriglyceridemia (sHTG), defined as a triglyceride (TG) concentration ≥ 500 mg/dL (≥ 5.7 mmol/L) is an important risk factor for acute pancreatitis. Although lifestyle, some medications, and certain conditions such as diabetes may lead to HTG, sHTG results from a combination of major and minor genetic defects in proteins that regulate TG lipolysis. Familial chylomicronemia syndrome (FCS) is a rare disorder caused by complete loss of function in lipoprotein lipase (LPL) or LPL activating proteins due to two homozygous recessive traits or compound heterozygous traits. Multifactorial chylomicronemia syndrome (MCS) and sHTG are due to the accumulation of rare heterozygous variants and polygenic defects that predispose individuals to sHTG phenotypes. Until recently, treatment of sHTG focused on lifestyle interventions, control of secondary factors, and nonselective pharmacotherapies that had modest TG-lowering efficacy and no corresponding reductions in atherosclerotic cardiovascular disease events. Genetic discoveries have allowed for the development of novel pathway-specific therapeutics targeting LPL modulating proteins. New targets directed towards inhibition of apolipoprotein C-III (apoC-III), angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like protein 4 (ANGPTL4), and fibroblast growth factor-21 (FGF21) offer far more efficacy in treating the various phenotypes of sHTG and opportunities to reduce the risk of acute pancreatitis and atherosclerotic cardiovascular disease events.
Topics: Humans; Acute Disease; Cardiovascular Diseases; Pancreatitis; Hyperlipoproteinemia Type I; Hypertriglyceridemia; Angiopoietin-Like Protein 3
PubMed: 37848164
DOI: 10.1016/j.pharmthera.2023.108544 -
QJM : Monthly Journal of the... Sep 2023
Topics: Humans; Hypertriglyceridemia; Pancreatitis; Acute Disease
PubMed: 37052536
DOI: 10.1093/qjmed/hcad063 -
Revista Do Colegio Brasileiro de... 2023The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was... (Review)
Review
The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was restricted to respiratory symptoms only, until extrapulmonary manifestations were reported worldwide. Acute pancreatitis concomitant with the diagnosis of SARS-CoV-2 infection has been observed in some patients, in the absence of the most common etiologies described in the literature. It is postulated that the presence of the ECA-2 viral receptor in the pancreas is responsible for the direct cellular damage and that the hyperinflammatory state of COVID-19 favors the development of pancreatitis through an immune-mediated mechanism. This study aimed to analyze the correlation between acute pancreatitis and COVID-19 disease as a probable causality factor. An integrative literature review was carried out, including studies published between January 2020 and December 2022 that brought data on patients diagnosed with acute pancreatitis according to the revised Atlanta Classification with a confirmed diagnosis of COVID-19 in the same period. A total of thirty studies were reviewed. Demographic, clinical, laboratory and imaging aspects were analyzed and discussed. It is believed that SARS-CoV-2 was responsible for the development of acute pancreatitis in these patients, due to the absence of other precipitating risk factors, as well as the close temporal relationship between both. Attention should be given to gastrointestinal manifestations in patients affected by COVID-19.
Topics: Humans; COVID-19; Pancreatitis; SARS-CoV-2; Acute Disease; Pancreas
PubMed: 37436286
DOI: 10.1590/0100-6991e-20233559-en -
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