Balanced hydroxyethylstarch (HES 130/0.4) impairs kidney function in-vivo without inflammation

Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1–4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansio

Anthropogenic organic micro-pollutants and pathogens in the urban water cycle: assessment, barriers and risk communication (ASKURIS)

In urban areas, water often flows along a partially closed water cycle in which treated municipal wastewater is discharged into surface waters which are one source of raw waters used for drinking water supply. A number of organic micro-pollutants (OMP) can be found in different water compartments. In the near future, climatic and demographic changes will probably contribute to an increase of OMP and antibiotic-resistant pathogens in aquatic ecosystems. The occurrence of OMP, possible adverse effects on aquatic organisms and human health and the public perception must be carefully assessed to properly manage and communicate potentially associated risks and to implement appropriate advanced treatment options at the optimum location within the water cycle. Therefore, the interdisciplinary research project ASKURIS focuses on identification and quantification, toxicological assessment and removal of organic micro-pollutants and antibiotic-resistant pathogens in the Berlin water cycle, life cycle-based economic and environmental assessment, public perception and management of potential risks

DEMO diagnostics and burn control

The development of the control system for a tokamak demonstration fusion reactor (DEMO) faces unprecedented challenges. First, the requirements for control reliability and accuracy are more stringent than on existing fusion devices: any loss of plasma control on DEMO may result in a disruption which could damage the inner wall of the machine, while operating the device with larger margins against the operational limits would lead to a reduction of the electrical output power. Second, the performance of DEMO control is limited by space restrictions for the implementation of components (optimization of the tritium breeding rate), by lifetime issues for the front-end parts (neutron and gamma radiation, erosion and deposition acting on all components) and by slow, weak and indirect action of the available actuators (plasma shaping, heating and fuelling). The European DEMO conceptual design studies include the development of a reliable control system, since the details of the achievable plasma scenario and the machine design may depend on the actual performance of the control system. In the first phase of development, an initial understanding of the prime choices of diagnostic methods applicable to DEMO, implementation and performance issues, the interrelation with the plasma scenario definition, and the planning of necessary future R&D have been obtained

Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression

Objective: To investigate the impact of the phophodiesterase-4 inhibition (PD-4-I) with rolipram on hepatic integrity in lipopolysaccharide (LPS) induced hyperinflammation. Materials and Methods: Liver microcirculation in rats was obtained using intravital microscopy. Macrohemodynamic parameters, blood assays, and organs were harvested to determine organ function and injury. Hyperinflammation was induced by LPS and PD-4-I rolipram was administered intravenously one hour after LPS application. Cell viability of HepG2 cells was measured by EZ4U-kit based on the dye XTT. Experiments were carried out assessing the influence of different concentrations of tumor necrosis factor alpha (TNF-α) and LPS with or without PD-4-I. Results: Untreated LPS-induced rats showed significantly decreased liver microcirculation and increased hepatic cell death, whereas LPS + PD-4-I treatment could improve hepatic volumetric flow and cell death to control level whithout influencing the inflammatory impact. In HepG2 cells TNF-α and LPS significantly reduced cell viability. Coincubation with PD-4-I increased HepG2 viability to control levels. The heme oxygenase 1 (HO-1) pathway did not induce the protective effect of PD-4-I. Conclusion: Intravenous PD-4-I treatment was effective in improving hepatic microcirculation and hepatic integrity, while it had a direct protective effect on HepG2 viability during inflammation

Lower rate of delayed graft function is observed when epidural analgesia for living donor nephrectomy is administered

Abstract Background The beneficial effects of epidural analgesia (EDA) in terms of pain control and postoperative convalescence are widely known and led to a frequent use for patients who underwent living donor kidney nephrectomy. The objective of this study was to determine whether general anesthesia (GA) plus EDA compared to GA only, administered for living donor nephrectomy has effects on postoperative graft function in recipients. Methods In this monocentric, retrospective cohort analysis we analyzed the closed files of all consecutive donor- recipient pairs who underwent living donor kidney transplantations from 2008 to 2017. The outcome variable was delayed graft function (DGF), defined as at least one hemodialysis within seven days postoperatively, once hyperacute rejection, vascular or urinary tract complications were ruled out. Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher exact test for categorical variables with a significance level of p < 0.05, respectively. Results The study enclosed 291 consecutive living donor kidney transplantations. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. The groups showed balanced pretransplantational characteristics and comparable donors´ and recipients’ risk factors. 9 out of all 291 recipients needed renal replacement therapy (RRT) during the first 7 days due to delayed graft function; none of these donors received EDA. The observed rate of DGF in recipients whose kidney donors received epidural analgesia was significantly lower (0% vs. 4.6%; p = 0.031). Conclusions In our cohort we observed a significantly lower rate of DGF when epidural analgesia for donor nephrectomy was administered. Due to restrictions of the study design this observation needs further confirmation by prospective studies

Risk Factors for Postoperative Pulmonary Complications Leading to Increased In-Hospital Mortality in Patients Undergoing Thoracotomy for Primary Lung Cancer Resection: A Multicentre Retrospective Cohort Study of the German Thorax Registry

Postoperative pulmonary complications (PPCs) represent the most frequent complications after lung surgery, and they increase postoperative mortality. This study investigated the incidence of PPCs, in-hospital mortality rate, and risk factors leading to PPCs in patients undergoing open thoracotomy lung resections (OTLRs) for primary lung cancer. The data from 1426 patients in this multicentre retrospective study were extracted from the German Thorax Registry and presented after univariate and multivariate statistical processing. A total of 472 patients showed at least one PPC. The presence of two PPCs was associated with a significantly increased mortality rate of 7% (p &lt; 0.001) compared to that of patients without or with a single PPC. Three or more PPCs increased the mortality rate to 33% (p &lt; 0.001). Multivariate stepwise logistic regression analysis revealed male gender (OR 1.4), age &gt; 60 years (OR 1.8), and current or previous smoking (OR 1.6), while the pre-operative risk factors were still CRP levels &gt; 3 mg/dl (OR 1.7) and FEV1 &lt; 60% (OR 1.4). Procedural independent risk factors for PPCs were: duration of surgery exceeding 195 min (OR 1.6), the amount of intraoperative blood loss (OR 1.6), partial ligation of the pulmonary artery (OR 1.5), continuing invasive ventilation after surgery (OR 2.9), and infusion of intraoperative crystalloids exceeding 6 mL/kg/h (OR 1.9). The incidence of PPCs was significantly lower in patients with continuous epidural or paravertebral analgesia (OR 0.7). Optimising perioperative management by implementing continuous neuroaxial techniques and optimised fluid therapy may reduce the incidence of PPCs and associated mortality

Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model

Background Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring. Methods Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days. Results All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days. Conclusions The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI

The KEY Approach: Integrating Object Oriented Design and Formal Verification

This paper reports on the ongoing KeY project aimed at bridging the gap between (a) object-oriented software engineering methods and tools and (b) deductive verification. A distinctive feature of our approach is the use of a commercial CASE tool enhanced with functionality for formal specifiation and deductive verification