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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

Diagnostic scoring systems for familial hypercholesterolaemia and familial chylomicronaemia syndrome often cannot differentiate between adults who have extreme dyslipidaemia based on a simple monogenic cause versus people with a more complex cause involving polygenic factors and an environmental component. This more complex group of patients carries a substantial risk of atherosclerotic cardiovascular disease in the case of marked hypercholesterolaemia and pancreatitis in the case of marked hypertriglyceridaemia. Complications are mainly a function of the degree of disturbance in lipid metabolism resulting in elevated lipid levels, so the added value of knowing the precise genetic cause in clinical decision making is unclear and does not lead to clinically meaningful benefit. We propose that for severe elevations of plasma low density lipoprotein cholesterol or triglyceride, the primary factor driving intervention should be the biochemical perturbation rather than the clinical risk score. This underscores the importance of expanding the definition of severe dyslipidaemias and to not rely solely on clinical scoring systems to identify individuals who would benefit from appropriate treatment approaches. We advocate for the use of simple, practical, clinical, and largely biochemically based definitions for severe hypercholesterolaemia (eg, LDL cholesterol >5 mmol/L) and severe hypertriglyceridaemia (triglyceride >10 mmol/L), which complement current definitions of familial hypercholesterolaemia and familial chylomicronaemia syndrome. Irrespective of the precise genetic cause, individuals diagnosed with severe hypercholesterolaemia and severe hypertriglyceridaemia require intensive therapy, including special consideration for new effective but more expensive therapies.
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PMID:Practical definitions of severe versus familial hypercholesterolaemia and hypertriglyceridaemia for adult clinical practice. 3144 54

l-Asparaginase (l-Asp) is a critical component of chemotherapy for acute lymphoblastic leukemia (ALL). However, toxic effects associated with l-Asp, such as hepatic dysfunction, pancreatitis, hypercholesterolemia, and hyperglycemia, have occurred. In addition, acute pancreatitis is a significant life-threatening adverse event associated with ALL. We describe 2 patients with ALL who had l-Asp-associated pancreatitis (AAP), with one patient presenting with hyperglycemia and the other presenting with hypoglycemia during induction treatment. When octreotide was administered to both of these patients, the clinical findings and laboratory data were improved. AAP was not repeated after treatment with pegylated asparaginase. Although AAP has a high risk of mortality and morbidity in childhood, APP treatment with appropriate agents, such as octreotide, can be successful.
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PMID:Successful Management of l-Asparaginase-Associated Pancreatitis With Octreotide and Pegylated Asparaginase in 2 Patients With Acute Lymphoblastic Leukemia: Is There a Different Rare Warning Sign of Hypoglycemia for l-Asparaginase-Associated Pancreatitis? 3218 14

As survival of acute lymphoblastic leukemia (ALL) exceeds 90%, limiting therapy-related toxicity has become a key challenge. Cardio-metabolic dysfunction is a challenge during and after childhood ALL therapy. In a single center study, we measured triglycerides (TG), total cholesterol (TC), high (HDL) and low density lipoproteins (LDL) levels at diagnosis and assessed the association with BMI, early therapy response, on-therapy hyperlipidemia and the toxicities; thromboembolism, osteonecrosis and pancreatitis. We included 127 children (1.0-17.9 years) all treated according to the NOPHO ALL2008 protocol. Dyslipidemia was identified at ALL-diagnosis in 99% of the patients, dominated by reduced HDL levels (98%) and mild hypertriglyceridemia (61%). Hypertriglyceridemia was not associated with body mass index (P = 0.71). Five percent of patients had mild hypercholesterolemia, 14% had mild hypocholesterolemia, 13% had decreased and 1% elevated LDL-levels. Increased TG and TC levels at ALL-diagnosis were not associated with any on-therapy lipid levels. Lipid levels and BMI were not associated to MRD after induction therapy; However, BMI and hypercholesterolemia were associated with worse risk group stratification (P<0.045 for all). The cumulative incidence of thromboembolism was increased both for patients with hypo- (20.0%) and hypercholesterolemia (16.7%) compared to patients with normal TC levels (2.2%) at diagnosis (P = 0.0074). In conclusion, dyslipidemic changes were present prior to ALL-therapy in children with ALL but did not seem to affect dysmetabolic traits during therapy and were not predictive of on-therapy toxicities apart from an association between dyscholesterolemia at time of ALL-diagnosis and risk of thromboembolism. However, the latter should be interpreted with caution due to low number in the groups.
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PMID:Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia. 3225 40


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