Cardiogenic Shock Management and Research: Past, Present, and Future Outlook

Although great strides have been made in the pathophysiological understanding, diagnosis and management of cardiogenic shock (CS), morbidity and mortality in patients presenting with the condition remain high. Acute MI is the commonest cause of CS; consequently, most existing literature concerns MI-associated CS. However, there are many more phenotypes of patients with acute heart failure. Medical treatment and mechanical circulatory support are well-established therapeutic options, but evidence for many current treatment regimens is limited. The issue is further complicated by the fact that implementing adequately powered, randomized controlled trials are challenging for many reasons. In this review, the authors discuss the history, landmark trials, current topics of medical therapy and mechanical circulatory support regimens, and future perspectives of CS management

Challenges in the association of human single nucleotide polymorphism mentions with unique database identifiers

Thomas PE, Klinger R, Furlong LI, Hofmann-Apitius M, Friedrich CM. Challenges in the association of human single nucleotide polymorphism mentions with unique database identifiers. BMC Bioinformatics. 2011;12(Suppl 4): S4

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Enzymatic cross-linking of pectin in a high-pressure foaming process

The enzyme laccase is a copper-containing oxidoreductase with the ability to oxidize a wide range of substrates, such as ferulic acid. Thus, the ferulic acid-containing sugar beet pectin (SBP) can be cross-linked through laccase-mediated oxidation. As cross-linking increases viscosity, it could be applied to stabilize SBP-containing foams. In this study, laccase-mediated cross-linking of SBP was investigated under conditions of a high-pressure foaming process. Shear, presence of CO2, and pressure were simulated in a rheometer equipped with a high-pressure cell. At rest, addition of laccase to SBP solution led to the formation of a stiff gel. Application of shear upon mixing of laccase and SBP solution decreased the storage modulus with increasing shear duration and shear rate. This can be attributed to the formation of a fluid gel. However, when shear was stopped before all available ferulic acid groups were cross-linked, a stronger and more coherent network was formed. Pressure exerted by CO2 did not affect cross-linking. Additionally, this approach was tested in a stirred high-pressure vessel where SBP was foamed through CO2 dissolution under pressure and shear followed by controlled pressure release. While pure SBP foam was highly unstable, addition of laccase decelerated collapse. Highest stability was reached when laccase and SBP were mixed prior to depressurization. At the point of foam formation, the continuous phase was thereby viscous enough to increase foam stability. At the same time, continuation of cross-linking at rest caused gel templating of the foam structure.ISSN:2042-6496ISSN:2042-650

The novel adenosine A_2A antagonist prodrug MSX-4 is effective in animal models related to motivational and motor functions

Adenosine A2A and dopamine D2 receptors interact to regulate diverse aspects of ventral and dorsal striatal functions related to motivational and motor processes, and it has been suggested that adenosine A2A antagonists could be useful for the treatment of depression, parkinsonism and other disorders. The present experiments were performed to characterize the effects of MSX-4, which is an amino acid ester prodrug of the potent and selective adenosine A2A receptor antagonist MSX-2, by assessing its ability to reverse pharmacologically induced motivational and motor impairments. In the first group of studies, MSX-4 reversed the effects of the D2 antagonist eticlopride on a concurrent lever pressing/chow feeding task that is used as a measure of effort-related choice behavior. MSX-4 was less potent after intraperitoneal administration than the comparison compound, MSX-3, though both were equally efficacious. With this task, MSX-4 was orally active in the same dose range as MSX-3. MSX-4 also reversed the locomotor suppression induced by eticlopride in the open field, but did not induce anxiogenic effects as measured by the relative amount of interior activity. Behaviorally active doses of MSX-4 also attenuated the increase in c-Fos and pDARPP-32(Thr34) expression in nucleus accumbens core that was induced by injections of eticlopride. In addition, MSX-4 suppressed the oral tremor induced by the anticholinesterase galantamine, which is consistent with an antiparkinsonian profile. These actions of MSX-4 indicate that this compound could have potential utility as a treatment for parkinsonism, as well as some of the motivational symptoms of depression and other disorders

Continuous Glucose Monitoring in Patients Undergoing Extracorporeal Ventricular Assist Therapy

<div><p>Background</p><p>Dysregulations of blood glucose (BG) are associated with adverse outcome in critical illness; controlling BG to target appears to improve outcome. Since BG-control is challenging in daily intensive care practice BG-control remains poor especially in patients with rapidly fluctuating BG. To improve BG-control and to avoid deleterious hypoglycemia, automated online-measurement tools are advocated. We thus evaluated the point-accuracy of the subcutaneous Sentrino^® Continuous Glucose Monitoring System (CGM, Medtronic Diabetes, Northridge, California) in patients undergoing extracorporeal cardiac life support (ECLS) for cardiogenic shock.</p><p>Methods</p><p>Management of BG was performed according to institute’s standard aiming at BG-levels between 100–145 mg/dl. CGM-values were recorded without taking measures into therapeutic account. Point-accuracy in comparison to intermittent BG-measurement by the ABL-blood-gas analyzer was determined.</p><p>Results</p><p>CGM (n = 25 patients) correlated significantly with ABL-values (r = 0.733, p<0.001). Mean error from standard was 15.0 mg/dl (11.9%). 44.2% of the readings were outside a 15% range around ABL-values. In one of 635 paired data-points, ABL revealed hypoglycemia (BG 32 mg/dl) whereas CGM did not show hypoglycemic values (132mg/dl).</p><p>Conclusions</p><p>CGM reveals minimally invasive BG-values in critically ill adults with dynamically impaired tissue perfusion. Because of potential deviations from standard, CGM-readings must be interpreted with caution in specific ICU-populations.</p></div

Clarke Error Grid Analysis.

<p>Zone A: Clinically accurate, Zone B: Benign, Zone C: Overcorrected, Zone D: Failure to detect, Zone E: Erroneus.</p

Demographic data.

<p>Demographic data.</p

Regression analysis, Pearson correlation: 0.733398, significance (2-tailed), p = 0.000.

<p>Regression analysis, Pearson correlation: 0.733398, significance (2-tailed), p = 0.000.</p