[Curriculum "Tracheostomy management in dysphagia therapy"]. / Curriculum "Trachealkanülenmanagement in der Dysphagietherapie".

The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM.

[Curriculum "Tracheostomy management in dysphagia therapy"]. / Curriculum "Trachealkanülenmanagement in der Dysphagietherapie".

The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM.

Response of Arthrospira platensis to different temperatures regarding growth and biochemical composition.

The growth of cyanobacteria can vary considerably depending on the ambient temperature. Since the optimal growth temperature for Arthrospira platensis (strain SAG21.99) is not yet known, this was investigated in the present study. The study revealed that a process temperature of 30 °C seems to be optimal for the Arthrospira strain SAG21.99 cultivation in terms of a maximum biomass productivity. This was also true for the phycocyanin content which was at 30 °C significantly higher than at 20 or 40 °C.

Effect of Arthrospira powders from different producers on the formation of endothelial cell monolayers.

Arthrospira platensis (AP) and some of its derived products have well-established biological activities as antioxidants or as agents to reduce cardiovascular disease risk factors. Furthermore, AP products have gained increasing importance as potential anti-cancer agents. However, the ingredients of the available products vary greatly with the origin, the type of production and processing, which could have significant consequences for their biological effects. Therefore, the composition and biological influence of five distinct AP powders, which were acquired commercially or produced at a public biotechnology institute, were investigated in regard to their endothelialization capacity using a cell impedance- (CI) based measurement method. The study revealed that the AP composition and especially the influence on HUVEC proliferation differed significantly between the five AP powders up to 109%.Thus, it could be shown that the method used allows the reliable detection of quantitative differences in biological effects of different AP preparations.

[Core curriculum Medical intensive care medicine of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN)]. / Curriculum Internistische Intensivmedizin.

Medical intensive care medicine treats patients with severe, potentially life-threatening diseases covering the complete spectrum of internal medicine. The qualification in medical intensive care medicine requires a broad spectrum of knowledge and skills in medical intensive care medicine, but also in the general field of internal medicine. Both sides of the coin must be taken into account, the treatment with life-sustaining strategies of the acute illness of the patient and also the treatment of patient's underlying chronic diseases. The indispensable foundation of medical intensive care medicine as described in this curriculum includes basic knowledge and skills (level of competence I-III) as well as of behavior and attitudes. This curriculum is primarily dedicated to the internist in advanced training in medical intensive care medicine. However, this curriculum also intends to reach trainers in intensive care medicine and also the German physician chambers with their examiners, showing them which knowledge, skills as well as behavior and attitudes should be taught to trainees according to the education criteria of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN).

Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels.

Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the "Hen's egg test on chorioallantoic membrane" (HET-CAM) test and a mouse model.The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants.

The influence of different rewetting procedures on the thrombogenicity of nanoporous poly(ether imide) microparticles.

Nanoporous microparticles prepared from poly(ether imide) (PEI) are discussed as candidate adsorber materials for the removal of uremic toxins during apheresis. Polymers exhibiting such porosity can induce the formation of micro-gas/air pockets when exposed to fluids. Such air presenting material surfaces are reported to induce platelet activation and thrombus formation. Physical or chemical treatments prior to implantation are discussed to reduce the formation of such gas nuclei. Here, we report about the influence of different rewetting procedures - as chemical treatments with solvents - on the thrombogenicity of hydrophobic PEI microparticles and PEI microparticles hydrophilized by covalent attachment of poly(vinyl pyrrolidone) (PVP) of two different chain lengths.Autoclaved dry PEI particles of all types with a diameter range of 200 - 250 µm and a porosity of about 84% ±2% were either rewetted directly with phosphate buffered saline (24 h) or after immersion in an ethanol-series. Thrombogenicity of the particles was studied in vitro upon contact with human sodium citrated whole blood for 60 min at 5 rpm vertical rotation. Numbers of non-adherent platelets were quantified, and adhesion of blood cells was qualitatively analyzed by bright field microscopy. Platelet activation (percentage of CD62P positive platelets and amounts of soluble P-Selectin) and platelet function (PFA100 closure times) were analysed.Retention of blood platelets on the particles was similar for all particle types and both rewetting procedures. Non-adherent platelets were less activated after contact with ethanol-treated particles of all types compared to those rewetted with phosphate buffered saline as assessed by a reduced number of CD62P-positive platelets and reduced amounts of secreted P-Selectin (P < 0.05 each). Interestingly, the hydrophilic surfaces significantly increased the number of activated platelets compared to hydrophobic PEI regardless of the rewetting agent. This suggests that, apart from wettability, other material properties might be more important to regulate platelet activation. PFA100 closure times were reduced and within the reference ranges in the ethanol group, however, significantly increased in the saline group. No substantial difference was detected between the tested surface modifications. In summary, rewetting with ethanol resulted in a reduced thrombogenicity of all studied microparticles regardless of their wettability, most likely resulting from the evacuation of air from the nanoporous particles.

Health status of free-ranging ring-necked pheasant chicks (Phasianus colchicus) in North-Western Germany.

Being a typical ground-breeding bird of the agricultural landscape in Germany, the pheasant has experienced a strong and persistent population decline with a hitherto unexplained cause. Contributing factors to the ongoing negative trend, such as the effects of pesticides, diseases, predation, increase in traffic and reduced fallow periods, are currently being controversially discussed. In the present study, 62 free-ranging pheasant chicks were caught within a two-year period in three federal states of Germany; Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein. The pheasant chicks were divided into three age groups to detect differences in their development and physical constitution. In addition, pathomorphological, parasitological, virological, bacteriological and toxicological investigations were performed. The younger chicks were emaciated, while the older chicks were of moderate to good nutritional status. However, the latter age group was limited to a maximum of three chicks per hen, while the youngest age class comprised up to ten chicks. The majority of chicks suffered from dermatitis of the periocular and caudal region of the head (57-94%) of unknown origin. In addition, intestinal enteritis (100%), pneumonia (26%), hepatitis (24%), perineuritis (6%), tracheitis (24%), muscle degeneration (1%) and myositis (1%) were found. In 78% of the cases, various Mycoplasma spp. were isolated. Mycoplasma gallisepticum (MG) was not detected using an MG-specific PCR. Parasitic infections included Philopteridae (55%), Coccidia (48%), Heterakis/Ascaridia spp. (8%) and Syngamus trachea (13%). A total of 8% of the chicks were Avian metapneumovirus (AMPV) positive using RT-PCR, 16% positive for infectious bronchitis virus (IBV) using RT-PCR, and 2% positive for haemorrhagic enteritis virus (HEV) using PCR. All samples tested for avian encephalomyelitis virus (AEV), infectious bursal disease virus (IBDV) or infectious laryngotracheitis virus (ILTV) were negative. The pool samples of the ten chicks were negative for all acid, alkaline-free and derivative substances, while two out of three samples tested were positive for the herbicide glyphosate. Pheasant chick deaths may often have been triggered by poor nutritional status, probably in association with inflammatory changes in various tissues and organs as well as bacterial and parasitic pathogens. Theses impacts may have played a major role in the decline in pheasant populations.

Framework for personalized prediction of treatment response in relapsing remitting multiple sclerosis.

BACKGROUND: Personalized healthcare promises to successfully advance the treatment of heterogeneous neurological disorders such as relapsing remitting multiple sclerosis by addressing the caveats of traditional healthcare. This study presents a framework for personalized prediction of treatment response based on real-world data from the NeuroTransData network. METHODS: A framework for personalized prediction of response to various treatments currently available for relapsing remitting multiple sclerosis patients was proposed. Two indicators of therapy effectiveness were used: number of relapses, and confirmed disability progression. The following steps were performed: (1) Data preprocessing and selection of predictors according to quality and inclusion criteria; (2) Implementation of hierarchical Bayesian generalized linear models for estimating treatment response; (3) Validation of the resulting predictive models based on several performance measures and routines, together with additional analyses that focus on evaluating the usability in clinical practice, such as comparing predicted treatment response with the empirically observed course of multiple sclerosis for different adherence profiles. RESULTS: The results revealed that the predictive models provide robust and accurate predictions and generalize to new patients and clinical sites. Three different out-of-sample validation schemes (10-fold cross-validation, leave-one-site-out cross-validation, and excluding a test set) were employed to assess generalizability based on three different statistical performance measures (mean squared error, Harrell's concordance statistic, and negative log-likelihood). Sensitivity to different choices of the priors, to the characteristics of the underlying patient population, and to the sample size, was assessed. Finally, it was shown that model predictions are clinically meaningful. CONCLUSIONS: Applying personalized predictive models in relapsing remitting multiple sclerosis patients is still new territory that is rapidly evolving and has many challenges. The proposed framework addresses the following challenges: robustness and accuracy of the predictions, generalizability to new patients and clinical sites and comparability of the predicted effectiveness of different therapies. The methodological and clinical soundness of the results builds the basis for a future support of patients and doctors when the current treatment is not generating the desired effect and they are considering a therapy switch. (A) The framework is developed using quality-proven real-world data of patients with relapsing remitting multiple sclerosis. Patients have heterogeneous individual characteristics and diverse disease profiles, indicated for example by variations in frequency of relapses and degree of disability. Longitudinal characteristics regarding disease history (e.g. number of previous relapses in the last 12 months) are extracted at the time of an intended therapy switch, i.e. at time point "Today" (left). All clinical parameters are captured in a standardized way (right). (B) The model predicts the course of the disease based on the observed data (panel A), and is able to account for the impact of various available therapies on chosen clinical endpoints. The resulting ranking of therapies has a dependency on patient characteristics, illustrated here by a different highest ranked therapy depending on the number of relapse in the previous 12 months. (C) The model is evaluated for various generalization properties. Compared to performance on the training set (gray) it is able to predict for new patients not part of the training set (red).Top: Prediction for new patients. Middle: Prediction for new clinical sites. Bottom: Prediction for different time windows. (D) In order to assess the clinical impact of the model, disease activity is compared between patients treated with the highest ranked therapy and those treated with any of the other therapies. Patients adhering to the highest ranked therapy are associated with a better disease outcome when compared to those who did not.

Age-related morphology and function of human arterial endothelial cells.

Endothelialization of cardiovascular implants is regarded as a promising strategy for long-term compatibility. While umbilical vein endothelial cells are typically applied in research, human arterial endothelial cells (HAEC) from elderly donors would be the obvious source for autologous cellularization strategies.In our approach, HAEC from 16 donors of varying age (16-63 years) were divided into two groups (<30 years and >30 years) and analyzed regarding morphology, viability, proliferation, function and senescence status.No age-related differences were found regarding morphology, viability, density, prostacyclin and nitrite secretion or collagen and laminin production. However, the metabolic activity was slightly decreased (p = 0.0374) and the membrane integrity marginally impaired (p = 0.0404) in cells from older donors. Two out of three senescence assays detected more senescence markers in cells from older donors.According to the assays applied here, HAEC from young and elderly donors up to the age of 63 years could be judged equally suitable for autologous cellularization strategies. However, this finding should be regarded with caution due to the extremely large variability between individual donors. Further studies comprising a larger sample size are necessary to investigate this issue more thoroughly.

Effects of acrolein in comparison to its prodrug cyclophosphamide on human primary endothelial cells in vitro.

Cyclophosphamide (CPA) is one of the most successful anticancer prodrugs that becomes effective after biotransformation in the liver resulting in the toxic metabolite acrolein. Cancer is often accompanied by thromboembolic events, which might be a result of dysfunctional endothelial cells due to CPA treatment. Here, the effect of 1 mM CPA or acrolein (10/50/100/500 µM) on human umbilical vein endothelial cells (HUVECs) was analyzed after two days of treatment. The addition of CPA or 10 µM acrolein did not affect HUVECs. However, concentrations of 100 µM and 500 µM acrolein significantly reduced the number of adherent cells by 86 ±â€¯13% and 99 ±â€¯1% and cell viability by 51 ±â€¯29% and 93 ±â€¯8% compared to the control. Moreover, pronounced stress fibers as well as multiple nuclei were observed and von Willebrand factor (vWF) was completely released. Lactate dehydrogenase was 8.5 ±â€¯7.0-fold and 252.9 ±â€¯42.9-fold increased showing a loss of cell membrane integrity. The prostacyclin and thromboxane secretion was significantly increased by the addition of 500 µM acrolein (43.1 ±â€¯17.6-fold and 246.4 ±â€¯106.3-fold) indicating cell activation/pertubation. High doses of acrolein led to HUVEC death and loss of vWF production. This effect might be associated with the increased incidence of thromboembolic events in cancer patients treated with high doses of CPA.

Spontaneous and induced platelet aggregation in apparently healthy subjects in relation to age.

Thrombotic disorders remain the leading cause of mortality and morbidity, despite the fact that anti-platelet therapies and vascular implants are successfully used today. As life expectancy is increasing in western societies, the specific knowledge about processes leading to thrombosis in elderly is essential for an adequate therapeutic management of platelet dysfunction and for tailoring blood contacting implants. This study addresses the limited available data on platelet function in apparently healthy subjects in relation to age, particularly in view of subjects of old age (80-98 years). Apparently healthy subjects between 20 and 98 years were included in this study. Platelet function was assessed by light transmission aggregometry and comprised experiments on spontaneous as well as ristocetin-, ADP- and collagen-induced platelet aggregation. The data of this study revealed a non-linear increase in the maximum spontaneous platelet aggregation (from 3.3% ±3.3% to 10.9% ±5.9%). The maximum induced aggregation decreased with age for ristocetin (from 85.8% ±7.2% to 75.0% ±7.8%), ADP (from 88.5% ±4.6% to 64.8% ±7.3%) and collagen (from 89.5% ±3.0% to 64.0% ±4.0%) in a non-linear manner (linear regression analysis). These observations indicate that during aging, circulating platelets become increasingly activated but lose their full aggregatory potential, a phenomenon that was earlier termed "platelet exhaustion". In this study we extended the limited existing data for spontaneous and induced platelet aggregation of apparently healthy donors above the age of 75 years. The presented data indicate that the extrapolation of data from a middle age group does not necessarily predict platelet function in apparently healthy subjects of old age. It emphasizes the need for respective studies to improve our understanding of thrombotic processes in elderly humans.

Influence of different surface treatments of poly(n-butyl acrylate) networks on fibroblasts adhesion, morphology and viability.

BACKGROUND: Physical and chemical characteristics of implant materials determine the fate of long-term cardiovascular devices. However, there is still a lack of fundamental understanding of the molecular mechanisms occurring in the material-tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno-compatible biomaterials with mechanical properties adjustable to blood vessels. Here we study the influence of different surface treatments in particular oxygen plasma modification and fibrinogen deposition as well as a combinatorial approach on the adhesion and viability of fibroblasts. MATERIAL AND METHODS: Two types of cPnBA networks with Young's moduli of 0.19±0.01 MPa (cPnBA04) and 1.02±0.01 MPa (cPnBA73) were synthesized and post-modified using oxygen plasma treatment (OPT) or fibrinogen coating (FIB) or a combination of both (OPT+FIB). The water contact angles of the differently post-treated cPnBAs were studied to monitor changes in the wettability of the polymer surfaces. Because of the key role of vascular fibroblasts in regeneration processes around implant materials, here we selected L929 fibroblasts as model cell type to explore morphology, viability, metabolic activity, cell membrane integrity as well as characteristics of the focal adhesions and cell cytoskeleton on the cPnBA surfaces. RESULTS: Compared to non-treated cPnBAs the advancing water-contact angles were found to be reduced after all surface modifications (p < 0.05, each), while lowest values were observed after the combined surface treatment (OPT+FIB). The latter differed significantly from the single OPT and FIB. The number of adherent fibroblasts and their adherence behavior differed on both pristine cPnBA networks. The fibroblast density on cPnBA04 was 743±434 cells·mm-2, was about 6.5 times higher than on cPnBA73 with 115±73 cells·mm-2. On cPnBA04 about 20% of the cells were visible as very small, round and buckled cells while all other cells were in a migrating status. On cPnBA73, nearly 50% of fibroblasts were visible as very small, round and buckled cells. The surface functionalization either using oxygen plasma treatment or fibrinogen coating led to a significant increase of adherent fibroblasts, particularly the combination of both techniques, for both cPnBA networks. It is noteworthy to mention that the fibrinogen coating overruled the characteristics of the pristine surfaces; here, the fibroblast densities after seeding were identical for both cPnBA networks. Thus, the binding rather depended on the fibrinogen coating than on the substrate characteristics anymore. While the integrity of the fibroblasts membrane was comparable for both polymers, the MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA. CONCLUSION: The applied surface treatments of cPnBA successfully improved the adhesion of viable fibroblasts. Under resting conditions as well as after shearing the highest fibroblast densities were found on surfaces with combined post-treatment.

Investigation into diseases in free-ranging ring-necked pheasants (Phasianus colchicus) in northwestern Germany during population decline with special reference to infectious pathogens.

The population of ring-necked pheasants (Phasianus colchicus) is decreasing all over Germany since the years 2008/2009. Besides impacts of habitat changes caused by current rates of land conversion, climatic influences or predators, a contribution of infectious pathogens needs also to be considered. Infectious and non-infectious diseases in free-living populations of ring-necked pheasants have been scarcely investigated so far. In the present study, carcasses of 258 deceased free-ranging pheasants of different age groups, predominantly adult pheasants, collected over a period of 4 years in the states of Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein, were examined pathomorphologically, parasitologically, virologically and bacteriologically, with a focus set on infectious pathogens. A periocular and perinasal dermatitis of unknown origin was present in 62.3% of the pheasants. Additional alterations included protozoal cysts in the skeletal musculature (19.0%), hepatitis (21.7%), enteritis (18.7%), gastritis (12.6%), and pneumonia (11.7%). In single cases, neoplasms (2.6%) and mycobacteriosis (1.7%) occurred. Further findings included identification of coronaviral DNA from trachea or caecal tonsils (16.8%), siadenoviral DNA (7.6%), avian metapneumoviral RNA (6.6%), and infectious bursal disease viral RNA (3.7%). Polymerase chain reaction (PCR) on herpesvirus, avian influenza virus (AIV), paramyxovirus type 1 (PMV-1), avian encephalomyelitis virus (AEV), and chlamydia were negative. Based on the present results, there is no indication of a specific pathogen as a sole cause for population decline in adult pheasants. However, an infectious disease can still not be completely excluded as it may only affect reproduction effectivity or a certain age group of pheasants (e.g., chicks) which were not presented in the study.

[Life after ARDS]. / Das Leben nach ARDS.

Patients who survive acute respiratory distress syndrome (ARDS) often suffer from long-term physical and psychological sequelae. Lung function is commonly only mildly reduced, whereas general physical activity and walking distance are often compromised. Most markedly, these patients have a high incidence of depression, anxiety, and posttraumatic stress disorder. The rate of cognitive dysfunction is as high as 70-100% at the time of hospital discharge, and remains 46-80% and 20% one year and five years post discharge, respectively. The possibility of returning to work is markedly limited. Because of these outcomes, preventative strategies must be identified to reduce the high prevalence of physical and psychological morbidity. Prevention and treatment of delirium as well as early and consequent mobilization and intensive care unit diaries are potentially beneficial.

Evaluation of platelet adhesion and activation on polymers: Round-robin study to assess inter-center variability.

The regulatory agencies provide recommendations rather than protocols or standard operation procedures for the hemocompatibility evaluation of novel materials e.g. for cardiovascular applications. Thus, there is a lack of specifications with regard to test setups and procedures. As a consequence, laboratories worldwide perform in vitro assays under substantially different test conditions, so that inter-laboratory and inter-study comparisons are impossible. Here, we report about a prospective, randomized and double-blind multicenter trial which demonstrates that standardization of in vitro test protocols allows a reproducible assessment of platelet adhesion and activation from fresh human platelet rich plasma as possible indicators of the thrombogenicity of cardiovascular implants. Standardization of the reported static in vitro setup resulted in a laboratory independent scoring of the following materials: poly(dimethyl siloxane) (PDMS), poly(ethylene terephthalate) (PET) and poly(tetrafluoro ethylene) (PTFE). The results of this in vitro study provide evidence that inter-laboratory and inter-study comparisons can be achieved for the evaluation of the adhesion and activation of platelets on blood-contacting biomaterials by stringent standardization of test protocols.

[Extracorporeal lung support]. / Extrakorporale Verfahren zur Lungenunterstützung.

Systems for extracorporeal lung support have recently undergone significant technological improvements leading to more effective and safe treatment. Despite limited scientific evidence these systems are increasingly used in the intensive care unit for treatment of different types of acute respiratory failure. In general two types of systems can be differentiated: devices for extracorporeal carbon dioxide removal (ECCO2R) for ventilatory insufficiency and devices for extracorporeal membrane oxygenation (ECMO) for severe hypoxemic failure. Despite of all technological developments extracorporeal lung support remains an invasive and a potentially dangerous form of treatment with bleeding and vascular injury being the two main complications. For this reason indications and contraindications should always be critically considered and extracorporeal lung support should only be carried out in centers with appropriate experience and expertise.

Strategy for the hemocompatibility testing of microparticles.

Polymer-based microparticles are applied as non-thrombogenic or thrombogenic materials in a wide variety of intra- or extra-corporeal medical devices. As demanded by the regulatory agencies, the hemocompatibility of these blood contacting biomaterials has to be evaluated in vitro to ensure that the particle systems appropriately fulfill the envisioned function without causing undesired events such as thrombosis or inflammation. Currently described in vitro assays for hemocompatibility testing of particles comprise tests with different single cell types (e.g. erythrocytes or leukocytes), varying concentrations/dilutions of the used blood cells or whole blood, which are not standardized.Here, we report about an in vitro dynamic test system for studying the hemocompatibility of polymeric microparticles utilizing fresh human whole blood from apparently healthy subjects, collected and processed under standardized conditions. Spherical poly(ether imide) microparticles with an average diameter of 140±30 µm were utilized as model systems. Reported as candidate materials for the removal of uremic toxins, these microparticles are anticipated to facilitate optimal flow conditions in a dialyzer with minimal backflow and blood cell damage. Pristine (PEI) and potassium hydroxide (PEI-KOH) functionalized microparticles exhibited similarly nanoporous surfaces (PEI: ØExternal pore = 90±60 nm; PEI-KOH ØExternal pore = 150±130 nm) but varying water wettabilities (PEI: θadv = 112±10° PEI-KOH θadv = 60±2°). The nanoporosity of the microparticle surfaces allows the exchange of toxic solutes from blood towards the interconnective pores in the particle core, while an immigration of the substantially larger blood cells is inhibited.Sterilized PEI microparticles were incorporated -air-free -in a syringe-based test system and exposed to whole blood for 60 minutes under gentle agitation. Thereafter, thrombi formation on the particles surfaces were analyzed microscopically. In the collected whole blood the non-adherent/circulating single blood cells were quantified via a differentiated complete blood cell count and the activation of platelets (P-Selectin expression, secretion and release), platelet function (PFA100 closure time) as well as thrombin formation (thrombin-antithrombin-complex) was analyzed. Free hemoglobin (HGB) levels were quantified as a measure of hemolysis.Microscopic evaluation revealed thrombi formation and particle aggregates for all tested microparticles. Reduction of circulating blood cells differed significantly between the particle types. Particularly, platelet and monocyte counts decreased up to 50% compared to the control (syringe filled with whole blood but without microparticles). In accordance, platelet activation, thrombin levels and degrees of hemolysis were clearly elevated in the particle loaded test systems and allowed a differentiation between the particle types. Increased PFA100 closure times (as activating agent a combination of collagen/ADP was used) indicated a similarly reduced ability of platelets to adhere and form stable aggregates independent from the particle type tested. This observation is most probably a consequence of the strong thrombus formation in the test system, which is associated with a reduction of the circulating blood cells.The reported in vitro dynamic whole blood test system allowed the sensitive analysis of the hemocompatibility of polymer-based microparticles and was successfully validated for porous PEI microparticles with different water wettabilities. Beyond the qualitative and quantitative analysis of cell-material interactions, the test also allowed the functional evaluation of platelets in whole blood.

[Inadequate ICU-admissions : A 12-month prospective cohort study at a German University Hospital]. / Nicht indizierte Aufnahmen auf der Intensivstation : 12-Monats-Observationsstudie an einem Universitätsklinikum.

BACKGROUND: Intensive care medicine (ICM) is increasingly utilized by a growing number of critically ill patients worldwide. The reasons for this are an increasingly ageing and multimorbid population and technological improvements in ICM. Inappropriate patient admissions to the intensive care unit (ICU) can be a threat to rational resource allocation and to patient autonomy. OBJECTIVES: In this study, the incidence, characteristics, and resource utilization of patients inappropriately admitted to ICUs are studied. METHODS: This prospective study included all consecutive patients admitted from 01 September 2012 to 31 August 2013 to the Department of Intensive Care Medicine of a German university hospital comprised of 10 ICUs and 120 beds. Inappropriate admission was defined according to category 4B of the recommendations of the Society of Critical Care Medicine (SCCM; "futility of ICU treatment" or "ICU declined by patient") and was determined in each suspected case by structured group discussions between the study team and all involved care givers including the referring team. RESULTS: In all, 66 of 6452 ICU admissions (1 %) were suspected to have been inappropriate on retrospective evaluation the day after admission. In 50 patients (0.8 %), an interdisciplinary consensus was reached on the inappropriateness of the ICU admission. Of these 50 patients, 41 (82 %) had previously declined ICU treatment in principle. This information was based on the patient's presumed wish as expressed by next of kin (56 %) or in a written advanced directive (26 %). In 9 patients (18 %), ICU treatment was considered futile. In all cases, a lack of information regarding a patient's wishes or clinical prognosis was the reason for inappropriate ICU admission. CONCLUSION: In this study, patients were regularly admitted to the ICU despite their contrary wish/directive or an unfavorable clinical condition. Although this was registered in only 1 % of all admissions, optimizing preICU admission information flow with regard to relevant exclusion criteria not only helps respect patient autonomy but also allows for more adequate resource allocation.