Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs.

BACKGROUND: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. SOURCES OF MATERIAL: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. ABSTRACT OF FINDINGS: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. CONCLUSION: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk.

Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency.

BACKGROUND: Lipoprotein lipase (LPL) deficiency is a serious lipid disorder of severe hypertriglyceridemia (SHTG) with chylomicronemia. A large number of variants in the LPL gene have been reported but their influence on LPL activity and SHTG has not been completely analyzed. Gaining insight into the deleterious effect of the mutations is clinically essential. METHODS: We used gene sequencing followed by in-vivo/in-vitro and in-silico tools for classification. We classified 125 rare LPL mutations in 33 subjects thought to have LPL deficiency and in 314 subjects selected for very SHTG. RESULTS: Of the 33 patients thought to have LPL deficiency, only 13 were homozygous or compound heterozygous for deleterious mutations in the LPL gene. Among the 314 very SHTG patients, 3 were compound heterozygous for pathogenic mutants. In a third group of 51,467 subjects, from a general population, carriers of common variants, Asp9Asn and Asn291Ser, were associated with mild increase in triglyceride levels (11%-35%). CONCLUSION: In total, 39% of patients clinically diagnosed as LPL deficient had 2 deleterious variants. Three patients selected for very SHTG had LPL deficiency. The deleterious mutations associated with LPL deficiency will assist in the diagnosis and selection of patients as candidates for the presently approved LPL gene therapy.

Fecal elastase 1 measurement compared with endoscopic retrograde cholangiopancreatography for the diagnosis of chronic pancreatitis.

INTRODUCTION: Indirect tests of exocrine pancreatic function are thought to be of little sensitivity and specificity in mild to moderate insufficiency as compared with direct function tests. Direct tests, which are claimed to be the "gold standard" of functional diagnosis, are too complicated to be performed on great numbers of patients and are not standardized. AIMS: To characterize the use of an indirect function test (fecal elastase 1 measurements determined independently from a direct test), in this study we compared it with the gold standard of morphologic diagnosis, endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: Data for 213 patients who underwent ERCP (104 males and 109 females; mean age, 54 years [8-89]) were collected prospectively, including fecal elastase 1 measurements and clinical and ERCP data. RESULTS: Elastase 1 findings correlated with pancreatic duct changes (p < 0.05). At a cutoff point of 200 microg/g, the positive predictive value of elastase 1 measurement for moderate/severe duct changes was 90.4%, and for any duct changes it was 96.8%. The sensitivity was only 45.3% for any duct changes but 76.5% for severe changes. Specificity for moderate/severe changes was 86%. CONCLUSION: Fecal elastase 1 measurements appear to be valuable for characterizing patients at high risk for chronic pancreatitis, even if their sensitivity is lower than that of direct tests.

Chronic pancreatitis and diabetes mellitus. A retrospective analysis of 156 ERCP investigations in patients with insulin-dependent and non-insulin-dependent diabetes mellitus.

BACKGROUND: Pancreatic exocrine dysfunction has been described frequently in IDDM and NIDDM patients. Most authors tried to explain this finding as a diabetic complication. On the other hand, diabetes secondary to chronic pancreatitis (CP) might be more common than believed so far. AIM OF THE STUDY: In this study we evaluated pancreatograms of patients with known diabetes mellitus in order to detect ductal morphology changes characteristic for CP. METHODS: Consecutive diabetic patients admitted for ERCP for different reasons were evaluated retrospectively concerning ERCP findings, especially pancreatic duct changes (Cambridge classification), diabetes type, duration and therapy. RESULTS: 156 patients (76 male, 80 female; mean age 60 years (19-93)) were studied (38 IDDM; 118 NIDDM). Pancreatic ducts were classified as normal in 23.3%, CP degree I in 22.7%, CP degree II in 32.7% and CP degree III in 21.3%. The duct changes did not correlate with diabetes type (p = 0.19), diabetes duration (p = 0.38), diabetes therapy (p = 0.5) or age (p = 0.48). CONCLUSION: Since CP should be defined by morphological and functional changes, it must be concluded that a substantial number of patients with a primary diagnosis of diabetes mellitus may have CP as a concomitant disease or, more likely, as a cause for their diabetic state.