Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of lipid disorders is alarmingly increasing in the Western world. They are the result of either primary causes, such as unhealthy lifestyle choices or inherited risk factors, or secondary causes like other diseases or medication. Atypical changes in the synthesis, processing and catabolism of lipoprotein particles may lead to severe hypercholesterolemia, hypertriglyceridemia or elevated Lp(a). Although cholesterol-lowering drugs are the most prescribed medications, not all patients achieve guideline recommended cholesterol levels with the current treatment options, emphasising the need for new therapies. Also, some lipid disorders do not have any treatment options but rely only on stringent dietary restriction. Patients with untreated lipid disorders carry a severe risk of cardiovascular disease, diabetes, non-alcoholic fatty liver disease and pancreatitis among others. To achieve better treatment outcome, novel selective gene expression and epigenetic targeting therapies are constantly being developed. Therapeutic innovations employing targeted RNA technology utilise small interfering RNAs, antisense oligonucleotides, long non-coding RNAs and microRNAs to regulate target protein production whereas viral gene therapy provides functional therapeutic genes and CRISPR/Cas technology relies on gene editing and transcriptional regulation. In this review, we will discuss the latest advances in clinical trials for novel lipid-lowering therapies and potential new targets in pre-clinical phase.
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PMID:Recent advances in novel therapies for lipid disorders. 3122 25

Eruptive xanthoma is characterized by yellowish skin papules encircled by an erythematous halo and associated with severe hypertriglyceridemia above 2,000 mg/dl. Hypertriglyceridemia can be caused by primary genetic mutations, secondary causes, such as uncontrolled diabetes, obesity, alcohol overuse, or combinations of both. Eruptive xanthoma can serve as an important clinical indicator of underlying systemic conditions (e.g. hypertriglyceridemia and uncontrolled diabetes mellitus). It is important for clinicians to recognize it to prevent further complications such as pancreatitis and cardiovascular disease.
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PMID:Eruptive xanthoma associated with severe hypertriglyceridemia and poorly controlled type 1 diabetes mellitus. 3152 86

Background. Familial dysbetalipoproteinemia (also known as type 3 hyperlipoproteinemia) is typically associated with homozygosity for the apolipoprotein E2 isoform, but also sometimes with dominant rare missense variants in the APOE gene. Patients present with roughly equimolar elevations of cholesterol and triglyceride (TG) due to pathologic accumulation of remnant lipoprotein particles. Clinical features include tuberoeruptive xanthomas, palmar xanthomas, and premature vascular disease. Case. A 48-year-old male presented with severe combined dyslipidemia: total cholesterol and TG were 11.5 and 21.4 mmol/L, respectively. He had dyslipidemia since his early 20s, with tuberous xanthomas on his elbows and knees. His body mass index was 42 kg/m2. He also had treated hypertension, mild renal impairment, and a history of gout. He had no history of cardiovascular disease, peripheral arterial disease, or pancreatitis. Multiple medications had been advised including rosuvastatin, ezetimibe, fenofibrate, and alirocumab, but his lipid levels were never adequately controlled. Genetic Analysis. Targeted next-generation sequencing identified (1) the APOE E2/E2 homozygous genotype classically described with familial dysbetalipoproteinemia; (2) in addition, one APOE E2 allele contained the rare heterozygous missense variant p.G145D, previously termed apo E-Bethesda; (3) a rare heterozygous APOC2 nonsense variant p.Q92X; and (4) a high polygenic risk score for TG levels (16 out of 28 TG-raising alleles) at the 82nd percentile for age and sex. Conclusion. The multiple genetic "hits" on top of the classical APOE E2/E2 genotype likely explain the more severe dyslipidemia and refractory clinical phenotype.
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PMID:Severe Combined Dyslipidemia With a Complex Genetic Basis. 3153 26

Introduction: Hypertriglyceridemia is associated with both the development of cardiovascular disease (CVD) when mild-to-moderate and high risk of pancreatitis when more severe. The residual CVD risk after low-density lipoprotein cholesterol (LDL-C) lowering is, in part, attributed to high triglyceride (TG) levels. Therefore, there appears to be a need for effective TG-lowering agents.Areas covered: This review presents the most recent advances in hypertriglyceridemia treatment; specifically, it discusses the results of clinical trials and critically comments on apolipoprotein C-III inhibitors, angiopoietin-like 3 inhibitors, alipogene tiparvovec, pradigastat, pemafibrate and novel formulations of omega-3 fatty acids.Expert opinion: In the era of extreme lowering of LDL-C levels with several agents, there seems to be space for novel therapeutic options to combat parameters responsible for residual CVD risk, among which are elevated TGs. Furthermore, a significant number of individuals have very high TG levels and encounter the risk of acute pancreatitis. The most recently developed TG-lowering drugs appear to have a role in both conditions; the choice is mainly based on baseline TG levels. Dyslipidemia guidelines are likely to change in the near future to include some of these agents. Of course, long-term data regarding their safety and efficacy in terms of CVD outcomes and pancreatitis are warranted.
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PMID:Recent developments in pharmacotherapy for hypertriglyceridemia: what's the current state of the art? 3173 17

Hyperlipidemia,as one of the severe risk factors of cardiovascular disease,could easily trigger atherosclerosis,coronary heart disease,peripheral vascular disease,pancreatitis,etc.,and could also increase the incidence of type 2 diabetes and fatty liver disease. Improving dyslipidemia could slow down the progression of atherosclerosis and reduce the risk of coronary heart disease. This is of great importance for prevention and treatment of cardiovascular disease. Phytosterols are natural active ingredients in plants. Many researches have shown that phytosterols have significant lipid-lowering activity,which could effectively lower blood cholesterol and triglyceride levels. Foods containing phytosterols have been widely used as therapeutic diets for improving dyslipidemia. In the early years,it was believed that the lipid-lowering effect of phytosterols was achieved by competitively inhibiting the absorption of dietary cholesterol in the intestine since phytosterols had similar chemical structures with cholesterol. In further researches in recent years,more progress has been made in the lipid-lowering mechanisms of phytosterols. In this paper,PubMed and Web of Science were used to review the cholesterol-lowering and triglyceride-lowering mechanisms of phytosterols according to the available data published,so as to use phytosterols more rationally in clinical application to improve hyperlipidemia and other induced diseases.
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PMID:[Advances in research on hypolipidemic mechanism of phytosterols]. 3187 47

Alcohol consumption has long been a part of human culture. However, alcohol consumption levels and alcohol consumption patterns are associated with chronic diseases. Overall, light and moderate alcohol consumption (up to 14 g per day for women and up to 28 g per day for men) may be associated with reduced mortality risk, mainly due to reduced risks for cardiovascular disease and type-2 diabetes. However, chronic heavy alcohol consumption and alcohol abuse lead to alcohol-use disorder, which results in physical and mental diseases such as liver disease, pancreatitis, dementia, and various types of cancer. Risk factors for alcohol-use disorder are largely unknown. Alcohol-use disorder and frequent heavy drinking have detrimental effects on personal health.
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PMID:Alcohol and Human Health: What Is the Evidence? 3220 32

Acute esophageal necrosis (AEN), or colloquially named "black esophagus," is a rare clinical condition often associated with ischemic injury to the esophagus secondary to splanchnic vasoconstriction during hypotensive episodes. We present a case of a 78-year-old man with extensive cardiovascular disease who was initially admitted for gallstone pancreatitis and possible cholangitis. His hospital course was complicated by possible sepsis secondary to aspiration pneumonia and hematemesis secondary to acute ischemic esophageal necrosis as noted on upper endoscopy. Interestingly, the patient only had a transient episode of hypotension (approximately 35 minutes) not requiring vasopressor support, which improved with fluid resuscitation, and endoscopic retrograde cholangiopancreatography (ERCP) done 3 days prior showed normal esophageal mucosa. Clinicians should be aware of the possibility of acute esophageal necrosis as a potential etiology of gastrointestinal (GI) bleed in patients with cardiovascular disease and sepsis.
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PMID:Acute Esophageal Necrosis in a Septic Patient with a History of Cardiovascular Disease. 3245 33

Hypertriglyceridemia, defined as fasting serum triglyceride levels of 150 mg per dL or higher, is associated with increased risk of cardiovascular disease. Severely elevated triglyceride levels (500 mg per dL or higher) increase the risk of pancreatitis. Common risk factors for hypertriglyceridemia include obesity, metabolic syndrome, and type 2 diabetes mellitus. Less common risk factors include excessive alcohol use, physical inactivity, being overweight, use of certain medications, and genetic disorders. Management of high triglyceride levels (150 to 499 mg per dL) starts with dietary changes and physical activity to lower cardiovascular risk. Lowering carbohydrate intake (especially refined carbohydrates) and increasing fat (especially omega-3 fatty acids) and protein intake can lower triglyceride levels. Moderate- to high-intensity physical activity can lower triglyceride levels, as well as improve body composition and exercise capacity. Calculating a patient's 10-year risk of atherosclerotic cardiovascular disease is pertinent to determine the role of medications. Statins can be considered for patients with high triglyceride levels who have borderline (5% to 7.4%) or intermediate (7.5% to 19.9%) risk. For patients at high risk who continue to have high triglyceride levels despite statin use, high-dose icosapent (purified eicosapentaenoic acid) can reduce cardiovascular mortality (number needed to treat = 111 to prevent one cardiovascular death over five years). Fibrates, omega-3 fatty acids, or niacin should be considered for patients with severely elevated triglyceride levels to reduce the risk of pancreatitis, although this has not been studied in clinical trials. For patients with acute pancreatitis associated with hypertriglyceridemia, insulin infusion and plasmapheresis should be considered if triglyceride levels remain at 1,000 mg per dL or higher despite conservative management of acute pancreatitis.
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PMID:Management of Hypertriglyceridemia: Common Questions and Answers. 3293 Dec 17

Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for the development of cardiovascular disease (CVD) in the population at large and for pancreatitis in about two percent of individuals with extremely high levels of triglycerides (TG). This manuscript summarizes the mechanisms underlying the development of HTG as well as its management, including emerging therapies targeted at specific molecular pathways.
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PMID:Hypertriglyceridemia-Causes, Significance, and Approaches to Therapy. 3298 91

Hypertriglyceridemia is one of the most common lipid abnormalities encountered in clinical practice. Many monogenic disorders causing severe hypertriglyceridemia have been identified, but in most patients triglyceride elevations result from a combination of multiple genetic variations with small effects and environmental factors. Common secondary causes include obesity, uncontrolled diabetes, alcohol misuse, and various commonly used drugs. Correcting these factors and optimizing lifestyle choices, including dietary modification, is important before starting drug treatment. The goal of drug treatment is to reduce the risk of pancreatitis in patients with severe hypertriglyceridemia and cardiovascular disease in those with moderate hypertriglyceridemia. This review discusses the various genetic and acquired causes of hypertriglyceridemia, as well as current management strategies. Evidence supporting the different drug and non-drug approaches to treating hypertriglyceridemia is examined, and an easy to adopt step-by-step management strategy is presented.
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PMID:Management of hypertriglyceridemia. 3304 51


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