Treatment options for severe hypertriglyceridemia (SHTG): the role of apheresis

Hypertriglyceridemia is associated with a number of severe diseases such as acute pancreatitis and coronary artery disease. In severe hypertriglyceridemia (SHTG, triglycerides > 1,000 mg/dL), rapid lowering of plasma triglycerides (TG) has to be achieved. Treatment regimes include nutritional intervention, the use of antihyperlipidemic drugs, and therapeutic apheresis. Apheretic treatment is indicated in medical emergencies such as hypertriglyceridemic pancreatitis

Management of toxic ingestions with the use of renal replacement therapy

Although rare, renal replacement therapy (RRT) for the treatment of the metabolic, respiratory and hemodynamic complications of intoxications may be required. Understanding the natural clearance of the medications along with their volume of distribution, protein binding and molecular weight will help in understanding the benefit of commencing RRT. This information will aid in choosing the optimal forms of RRT in an urgent setting. Overdose of common pediatric medications are discussed with suggestions on the type of RRT within this educational review

The Role of Ultrasound Examination in the Assessment of Suitability of Calcified Arteries for Vascular Access Creation—Mini Review

Arterial calcifications are present in 20–40% of patients with end-stage kidney disease and are more frequent among the elderly and diabetics. They reduce the possibility of arterio-venous fistula (AVF) formation and maturation and increase the likelihood of complications, especially distal ischemia. This review focuses on methods for detecting arterial calcifications and assessing the suitability of calcified arteries for providing inflow before the construction of an AVF. The importance of a clinical examination is stressed. A grading system is proposed for quantifying the severity of calcifications in the arteries of the arm with B-mode and Doppler ultrasound exams. Functional tests to assess the suitability of the artery to provide adequate inflow to the AVF are discussed, including Doppler indices (peak systolic velocity and resistive index during reactive hyperemia). Possible predictors of the development of distal ischemia are discussed (finger pressure, digital brachial index, acceleration and acceleration time), as well as the outcomes of AVFs placed on calcified arteries. It is concluded that a noninvasive ultrasound examination is probably the best tool for a morphologic and functional assessment of the arteries. An arterial assessment is of utmost importance if we are to create distal radiocephalic AVFs in our elderly patients whenever possible without burdening them with futile surgical attempts

The role of apheresis and insulin therapy in hypertriglyceridemic acute pancreatitis—a concise review

Abstract Severe hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP) and is involved in its pathogenesis. Chylomicrons increase blood viscosity and induce ischemia, while free fatty acids induce inflammation and distant organ damage. Conservative treatment options include fasting and insulin; limited evidence shows their comparable efficacy. Plasma exchange might provide more rapid lowering of triglycerides and amelioration of systemic effects of severe AP. Available data from controlled studies show only moderately faster lowering of triglycerides with apheresis (about 70% vs. 50% with conservative treatment within 24 h) and limited data from non-randomized studies show no improvement in clinical outcomes. New evidence is expected soon from ongoing large randomized trials. Until then, insulin may be used in mild HTG-AP and plasma exchange should be considered only in severe HTG-AP, especially if the decline of triglycerides with conservative treatment is slow, and in HTG-AP during pregnancy

Ammodytoxin A acceptor in bovine brain synaptic-membranes

Ammodytoxin A, the presynaptic neurotoxin from Vipera ammodytes ammodytes venom, was found to bind specifically and with high affinity to bovine cortex synaptic membrane preparation. The detected ammodytoxin A high-affinity binding was characterized by equilibrium binding analysis which revealed a single high-affinity binding site with Kd 4.13 nM and Bmax 6.67 pmoles/mg of membrane protein. 125I-ammodytoxin A was covalently cross-linked to its neuronal acceptor using a chemical cross-linking technique. As revealed by subsequent SDS-PAGE analysis and autoradiography, 125I-ammodytoxin A specifically attached to membrane components with apparent mol. wts 53,000-56,000. Besides by the native ammodytoxin A, the binding of radioiodinated ammodytoxin A to the neuronal acceptor was highly attenuated, also by other two iso-neurotoxins from V. a. ammodytes venom, ammodytoxins B and C, and neurotoxin crotoxin B from the venom of the South American rattlesnake (Crotalus durissus terrificus). Vipera berus berus phospholipase A2 was a weaker inhibitor, whereas nontoxic phospholipase A2, ammodytoxin I2 and myotoxic phospholipase A2 homologue, ammodytin L, both from V. a. ammodytes venom as well, were very weak inhibitors. No inhibitory effect on 125I-ammodytoxin A specific binding at all was, however, obtained with α-dendrotoxin, β-bungarotoxin and crotoxin A, respectively. Treatment of synaptic membranes with proteinase K and Staphylococcus aureus V-8 proteinase, a combination of PNGase F and neuroaminidase, heat or acid lowered the 125I-ammodytoxin A specific binding to various extents but never completely abolished it. The ammodytoxin A binding site in bovine synaptic membranes is thus most likely a combination of membrane glycoprotein acceptor and membrane phospholipids. As ammodytoxin A reduced the second negative component of the perineural waveform, measured on mouse triangularis sterni preparation, which is very likely a result of an inhibition of a fraction of the terminal K+ currents, the ammodytoxin A acceptor could well be connected with K+ channels

Factors affecting outcome in acute hypertriglyceridemic pancreatitis treated with plasma exchange: an observational cohort study.

OBJECTIVES: The optimal therapy for hypertriglyceridemic acute pancreatitis, especially the role of plasma exchange (PE), is not entirely clear. The aim of our large, single-center, observational, cohort study was to analyze the factors affecting outcome in hypertriglyceridemic pancreatitis treated with PE. METHODS: We included 111 episodes of hypertriglyceridemic pancreatitis treated with PE, which occurred in 103 different patients. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, triglycerides, delay to first PE, and PE treatment details were retrospectively obtained from the patients' records. The main outcome measures were length of hospitalization and in-hospital mortality. RESULTS: The patients were 47±9 years old and the median APACHE II score at first PE was 4 (inter-quartile range (IQR) 2-7). There was a seasonal variation in the incidence of hypertriglyceridemic pancreatitis, and the recurrence rate was 1.6% per year. Triglycerides at presentation did not correlate with APACHE II or influence the outcome. The mean reduction in triglycerides during PE was 59% (from 44±31 to 18±15 mmol/l), which was twice the reduction observed during conservative treatment (27% daily). The median hospital stay was 16 days (IQR 10-24) and in-hospital mortality was 5%. The median delay to first PE was 35 hours (IQR 24-52), and there was no difference in mortality in the early and late PE groups (7% vs. 6%, p = 0.79). The group with citrate anticoagulation during PE had a significantly lower mortality than the group with heparin anticoagulation (1% vs. 11%, p = 0.04), and citrate was an independent predictor also in the multivariate model (p = 0.049). CONCLUSIONS: PE effectively reduced serum triglycerides faster than could be expected with conservative treatment. The delay in PE therapy did not influence survival. We found that citrate anticoagulation during PE was associated with reduced mortality, which should be confirmed in a randomized study