How effectively will PCSK9 inhibitors allow retrieval of freedom from apheresis in cardiovascular high risk patients? - Estimates form a large single center

Lipoprotein apheresis (LA) has been the last-resort therapeutic option in patients suffering from limited pharmaceutical options to lower highly elevated low density lipoprotein cholesterol (LDL-C) levels. Facing the introduction of the proprotein convertase subtilisin/kexine type 9 (PCSK-9) inhibitors, it has been speculated that they might replace LA to a large extend. Given an efficacy of approx. 55-65% to lower LDL-C it is important to analyze whether this might be realistic i) for potential candidates in apheresis sites and ii) for the future structures of the sites themselves. We performed a review of our own single center, one of the largest apheresis centers in Germany to answer these questions. Therefore we analyzed all actively treated apheresis patients and identified those with the primary indication of LDL-C elevation. In a next step we used pre-apheresis LDL-C values to calculate expected LDL-C under three given models of PCSK9 inhibitor efficacy. Including other aspects such as the accompanying presence of elevated lipoprotein(a), we identified 11-17 patients among 29 patients undergoing treatment for insufficiently treated LDL-C (38-58%). In the total cohort of 112 patients this reflects 10-15% of all patients that might potentially stop apheresis therapy due to the availability of PCSK9 inhibitor therapy, which is in clear contrast to speculations on the future perspective of apheresis therapy

Low rate of infectious complications following immunoadsorption therapy without regular substitution of intravenous immunoglobulins

INTRODUCTION: Immunoadsorption (IA) is increasingly used instead of plasma exchange due to lower risk of side effects and a higher selectivity. As a consequence of the reduction of immunoglobulins (Ig), the rate of infectious complications might increase in those patients. We therefore aimed to investigate the infection rate following IA without intravenous IG (IVIG) substitution in our apheresis center, where patients do not receive IVIG on a regular basis. MATERIAL AND METHODS: We conducted a retrospective analysis of the IA treatments performed between 2010 and 2015 without IVIG substitution and collected data on patient age, diagnosis, number of IA treatments, serum levels of Ig, total protein, albumin, C-reactive protein (CRP) and infectious complications that occurred within 2 months after the IA treatment cycle. RESULTS: A total number of 52 patients (27 females) received at least 5 IA sessions using the following adsorbers: TheraSorb™-Ig (n = 3), TheraSorb™-Ig flex (n = 44), TheraSorb™ Ig pro (n = 1) and TheraSorb™-IgE (n = 5). The median number of treatment sessions was 8.8 [range 5-16], the median IgG reduction was 82 [11-99] %. Serum albumin was decreased by 8%. The median CRP levels remained normal until the end of therapy and within 2 months after that (3.10 and 4.30 mg/L respectively). Only 4 patients had infections (7.7%). Three of them received additional immunosuppressive therapy. CONCLUSIONS: Immunoadsorption leads to a significant reduction of IgG. CRP as inflammatory marker is not affected. Even without substitution of IVIG the complication rate directly linked with IA is low and questionable

Mikrofluidische Vorrichtung für Zellkulturexperimente und Verwendungen hiervon

Es wird eine mikrofluidische Vorrichtung für Zellkulturexperimente vorgestellt. Die mikrofluidische Vorrichtung enthält neben mindestens einem Zellgefäß zur Kultivierung von biologischen Zellen eine Vorrichtung zur Bewegung einer Flüssigkeit in dem Zellgefäß, ein Gerät zur Schädigung biologischer Zellen über elektromagnetische Strahlung, eine Steuereinheit zur Steuerung dieses Geräts und eine Vorrichtung zur Untersuchung der biologischen Zellen in dem Zellgefäß, wobei die Vorrichtung dazu geeignet ist, von biologischen Zellen aus dem Zellgefäß emittierte elektromagnetische Strahlung zu detektieren. Die vorgestellte mikrofluidische Vorrichtung hat den Vorteil, dass eine Schädigung gezielt in eine sehr geringe Menge biologischer Zellen eingeführt werden kann, wobei die Schädigung und deren Heilung anschließend auf molekularer Ebene ortsspezifisch und reproduzierbar verfolgt werden kann. Es wird daher vorgeschlagen, die mikrofluidische Vorrichtung zur Untersuchung der Schädigung, Regeneration und Interaktion von biologischen Zellen zu verwenden

Long-term follow-up of circulating oxidative stress markers in patients undergoing lipoprotein apheresis by Direct Adsorption of Lipids (DALI)

OBJECTIVE: Beyond its well-established efficacy in lowering atherogenic lipids and lipoproteins, DALI (Direct Adsorption of Lipids) apheresis has been shown to have acute anti-inflammatory and endothelium-protective effects. In the present study, we investigated long-term effects of DALI procedures on circulating oxidative stress markers. METHODS: Thirteen patients involved in the study underwent regular DALI apheresis for nearly two years. At sessions 1, 40 and 80 conventional lipid status and changes of systemic oxidative stress markers (oxidized LDL, anti-oxidized LDL antibodies, advanced oxidation protein products (AOPP), and myeloperoxidase (MPO)) were examined. RESULTS: DALI procedure efficiently reduced atherogenic lipids/lipoproteins. On day three after apheresis lipid parameters returned to pre-apheresis values. They showed no tendency to increase or to decrease over time. No significant differences were found between 1st, 40th and 80th sessions. In a similar way, levels of oxidative stress biomarkers acutely decreased after apheresis sessions and rebounded on day three after apheresis. No significant differences were observed between sessions 1, 40, and 80. CONCLUSION: DALI apheresis repeatedly decreases atherogenic lipid/lipoprotein profile and oxidative stress biomarker levels during each session. Among all investigated parameters no longitudinal effects over two years could be observed