Influence of Hydrolyzed Metal Ions and Surfactants on the Phase Transfer of Al2O3, SiO2, and SnO2.

There are various possibilities for changing the surface properties of particles. In this work, the charge reversal on different metal oxides with different electrolytes is investigated and whether this allows a change in wettability due to a subsequent adsorption of surfactants, e.g., sodium dodecyl sulfate (SDS). It is investigated if the materials of the particles differ only by the isoelectric point or if the surface chemistry of the materials has an influence on the charge reversal as well. Furthermore, the adsorption of SDS as an anionic surfactant is examined, which is also characterized by a second charge reversal and related to a sign change of the electrophoretic mobility µe. Finally, it is examined whether the adsorption of the hydrolyzed metal ions and the subsequent adsorption of SDS are effective enough to hydrophobize the particles and allow phase transfer from the aqueous to second nonaqueous liquid phase. In addition, the influence of pH is investigated because the hydrolyzed metal cations are formed only in a certain pH range, which means that the bridge formed between the particle surface and the surfactant works only in a certain pH range, which would allow pH-selective extraction of the particle system into the second nonaqueous liquid phase.

A brief introduction to PAs in Germany.

ABSTRACT: The first German physician assistant (PA) program began in 2005 at Steinbeis University in Berlin. Since 2005, there has been a rapid expansion of PA education, and 22 German universities have opened or are planning to develop PA programs. In fall 2021, about 1,100 PAs worked in Germany, mostly in the inpatient setting, with a scope of practice focused on delegation and the performance of medical and administrative activities. After completing a PA program, students are awarded a bachelor of science; programs also offer options for specialization. With no formal PA program-specific accreditation processes, the universities are responsible for ensuring the quality and content of PA courses. The profession is not regulated in Germany, and laws to guide PA education and scope of practice are necessary for the further development of the profession.

A cross-sectional survey of German PA employment and workforce entry.

OBJECTIVE: The contribution of physician assistants (PAs) to the German healthcare workforce has increased significantly since their introduction in 2005. From five training programs, the number has increased to the current 18, with 560 PAs awarded the PA bachelor of science degree as of 2020. Despite the growth, researchers lack systemic and reliable empirical data that provide insight into the German PA educational and professional profile. The German University Association Physician Assistant (DHPA) undertook the first nationwide cross-sectional survey on PAs in Germany to understand the German PA movement. This survey aimed to describe German PAs' entry into the profession and PA educational and job satisfaction. METHODS: PA alumni of all universities affiliated with the DHPA and all subscribers of the Facebook online social media platform PA Blog were invited to complete an online questionnaire. RESULTS: Of the 282 PAs who completed the survey, 77% were female and under age 25 years. Almost all (94%) were employed, predominantly as PAs (91%, 241 of 265), although some held other positions. Most worked full time (87%), with some citing child-care needs as reasons for part-time employment (n = 21). Few reported unemployment (1.4%, 4 of 282). Eighty-two percent said they would probably or very likely choose the same course of study again. Most employed participants found the inclusion of frequent rotations between didactic and clinical training in PA programs beneficial. However, a small number of participants (26.8%) agreed that German PA programs' didactic and clinical teaching objectives were well aligned. CONCLUSIONS: German PAs have a high level of satisfaction with their profession and report low unemployment. Improvement in the alignment of didactic and clinical educational objectives to improve academic qualifications and satisfaction emerged as an area of research.

Absolute quantification of selected photosynthetic electron transfer proteins in Chlamydomonas reinhardtii in the presence and absence of oxygen.

The absolute amount of plastocyanin (PC), ferredoxin-NADP+-oxidoreductase (FNR), hydrogenase (HYDA1), and ferredoxin 5 (FDX5) were quantified in aerobic and anaerobic Chlamydomonas reinhardtii whole cells using purified (recombinant) proteins as internal standards in a mass spectrometric approach. Quantified protein amounts were related to the estimated amount of PSI. The ratios of PC to FNR to HYDA1 to FDX5 in aerobic cells were determined to be 1.4:1.2:0.003:0. In anaerobic cells, the ratios changed to 1.1:1.3:0.019:0.027 (PC:FNR:HYDA1:FDX5). Employing sodium dithionite and methyl viologen as electron donors, the specific activity of hydrogenase in whole cells was calculated to be 382 ± 96.5 µmolH2 min-1 mg-1. Importantly, these data reveal an about 70-fold lower abundance of HYDA1 compared to FNR. Despite this great disproportion between both proteins, which might further enhance the competition for electrons, the alga is capable of hydrogen production under anaerobic conditions, thus pointing to an efficient channeling mechanism of electrons from FDX1 to the HYDA1.

The COSTA Study: Sternal Closure in High-Risk Patients - A Prospective Randomized Multicenter Trial.

BACKGROUND: Median sternotomy in patients with risk factors for wound healing is associated with high rates of postoperative wound infections and sternum instability. METHODS: A total of 338 patients with elective first median sternotomy and at least four predefined risk factors were randomized between Sternal Talon (Gebrüder Martin GmbH & Co. KG-KLS Martin Group, Tuttlingen, Germany) and wire cerclage. The primary end point was mediastinitis and/or sternal instability within 30 ± 5 days, and the secondary end points were mediastinitis and/or sternal instability within 60 ± 5 days; incidence of pneumonia during hospitalization within the first 30 (±5) days and chest pain intensity. RESULTS: The primary end point was reached in 10 Sternal Talon and 7 wire cerclage patients (6.2 vs. 4.7%, odds ratio [OR]: 1.3, 95% confidence interval [CI]: 0.5-3.6, p = 0.57) from 338 randomized patients. Sternal Talon group, n = 170 patients versus wire cerclage group, n = 168 patients. The differences between treatment groups with regard to the incidence of mediastinitis/sternum instability within the first 60 (±5) days after the primary sternum closure and the incidence of pneumonia during the hospitalization within the first 30 (±5) days were not statistically significant, either. We observed comparable rates of superficial surgical site infection (SSI) in Sternal Talon and wire cerclage patients (16.1 vs. 12.1%, OR: 1.4, 95% CI: 0.7-2.7, p = 0.31). CONCLUSION: According to these data, there is no statistically significant difference between Sternal Talon closure and wire cerclage in reducing the incidence of mediastinitis and superficial SSI after primary closure of median sternotomy in high-risk patients.

Twenty minutes of normothermic cardiac arrest in a pig model: the role of short-term hypothermia for neurological outcome.

INTRODUCTION: Cardiopulmonary resuscitation restores circulation, but with inconsistent blood-flow and pressures. Our recent approach using an extracorporeal life support system, named "controlled integrated resuscitation device" (CIRD), may lead to improved survival and neurological recovery after cardiac arrest (CA). The basic idea is to provide a reperfusion tailored to the individual patient by control of the conditions of reperfusion and the composition of the reperfusate. Hypothermia is one aspect of this concept. Here, we investigated the role of immediate short-term blood cooling after experimental CA and its influence on survival and neurological recovery. METHODS: Twenty-one pigs were exposed to 20 minutes of normothermic CA. Afterwards, CIRD was immediately started for 60 minutes in all animals and the heart was converted to a sinus rhythm. The pigs either received normothermic reperfusion (37°C, n=11) or the temperature was maintained at 32°C for the first 30 minutes (n=10). Thermometric, hemodynamic and serologic data were collected during the experiment. After weaning from CIRD, neurological recovery was assessed daily by a species-specific neurological deficit score (NDS; 0: normal; 500: brain death). RESULTS: One pig in each group could not be successfully resuscitated. Due to severe neurological deficits, only 6/11 animals in the normothermic group finished the observation time of seven days with an NDS of 37±34. In the hypothermic group, all nine surviving animals reached day seven with an NDS of 16±13. Analogous to the lower NDS, animals in the hypothermic group also showed lower neuron-specific enolase end values as a marker of brain injury. CONCLUSIONS: Within this experimental setting, immediate moderate and short-term hypothermia after CA improves survival and seems to result in statistically non-significant better neurological recovery.

Association of Ferredoxin:NADP+ oxidoreductase with the photosynthetic apparatus modulates electron transfer in Chlamydomonas reinhardtii.

Ferredoxins (FDX) and the FDX:NADP+ oxidoreductase (FNR) represent a key junction of electron transport downstream of photosystem I (PSI). Dynamic recruitment of FNR to the thylakoid membrane has been considered as a potential mechanism to define the fate of photosynthetically derived electrons. In this study, we investigated the functional importance of the association of FNR with the photosynthetic apparatus in Chlamydomonas reinhardtii. In vitro assays based on NADP+ photoreduction measurements as well as NMR chemical shift perturbation analyses showed that FNR preferentially interacts with FDX1 compared to FDX2. Notably, binding of FNR to a PSI supercomplex further enhanced this preference for FDX1 over FDX2, suggesting that FNR is potentially capable of channelling electrons towards distinct routes. NADP+ photoreduction assays and immunoblotting revealed that the association of FNR with the thylakoid membrane including the PSI supercomplex is impaired in the absence of Proton Gradient Regulation 5 (PGR5) and/or Proton Gradient Regulation 5-Like photosynthetic phenotype 1 (PGRL1), implying that both proteins, directly or indirectly, contribute to the recruitment of FNR to the thylakoid membrane. As assessed via in vivo absorption spectroscopy and immunoblotting, PSI was the primary target of photodamage in response to high-light stress in the absence of PGR5 and/or PGRL1. Anoxia preserved the activity of PSI, pointing to enhanced electron donation to O2 as the source of the observed PSI inactivation and degradation. These findings establish another perspective on PGR5/PGRL1 knockout-related phenotypes and potentially interconnect FNR with the regulation of photosynthetic electron transport and PSI photoprotection in C. reinhardtii.

Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure.

RATIONALE: In chronic heart failure, increased adrenergic activation contributes to structural remodeling and altered gene expression. Although adrenergic signaling alters histone modifications, it is unknown, whether it also affects other epigenetic processes, including DNA methylation and its recognition. OBJECTIVE: The aim of this study was to identify the mechanism of regulation of the methyl-CpG-binding protein 2 (MeCP2) and its functional significance during cardiac pressure overload and unloading. METHODS AND RESULTS: MeCP2 was identified as a reversibly repressed gene in mouse hearts after transverse aortic constriction and was normalized after removal of the constriction. Similarly, MeCP2 repression in human failing hearts resolved after unloading by a left ventricular assist device. The cluster miR-212/132 was upregulated after transverse aortic constriction or on activation of α1- and ß1-adrenoceptors and miR-212/132 led to repression of MeCP2. Prevention of MeCP2 repression by a cardiomyocyte-specific, doxycycline-regulatable transgenic mouse model aggravated cardiac hypertrophy, fibrosis, and contractile dysfunction after transverse aortic constriction. Ablation of MeCP2 in cardiomyocytes facilitated recovery of failing hearts after reversible transverse aortic constriction. Genome-wide expression analysis, chromatin immunoprecipitation experiments, and DNA methylation analysis identified mitochondrial genes and their transcriptional regulators as MeCP2 target genes. Coincident with its repression, MeCP2 was removed from its target genes, whereas DNA methylation of MeCP2 target genes remained stable during pressure overload. CONCLUSIONS: These data connect adrenergic activation with a microRNA-MeCP2 epigenetic pathway that is important for cardiac adaptation during the development and recovery from heart failure.

Body image after heart transplantation compared to mechanical aortic valve insertion.

OBJECTIVE: Heart transplantation (HT) obviously affects body image and integrity. However, there are very few empirical data post-transplant. METHODS: In a cross-sectional study, 57 HT patients were compared with 47 subjects with mechanical aortic valve replacement (AVR) using the Dresden-Body-Image questionnaire (DKB) and specific questions regarding integration of the organ/device. In addition, affective symptoms and quality of life (QoL) were assessed (12-Item Short-Form Health Survey and Hospital Anxiety and Depression Scale, HADS). RESULTS: DKB-35 scores did not differ. HT patients scored higher than AVR on specific questions regarding integration of the organ/device. AVR patients showed more affective disturbance and lower mental QoL than HT subjects. Affective scores correlated negatively with body image scores. Seventeen percent of all patients showed psychological distress (HADS scores >8). CONCLUSIONS: HT patients integrated the new organ well - and even better than AVR subjects did with the device. In general, our data corroborate a good adaptation process, in particular in HT patients. Similar to other reported data, a subgroup of 15-20% of patients shows stronger mental distress, including body image problems. These must be identified and treated by professionals. Patients with AVR deserve more attention in the future.

Short-term intervention to reduce anxiety before coronary artery bypass surgery--a randomised controlled trial.

AIMS AND OBJECTIVES: The aim of this study was to evaluate an intervention with individualised information and emotional support before coronary artery bypass grafting in a controlled randomised trial. BACKGROUND: Anxiety is a typical phenomenon in patients who are to undergo cardiac surgery. Preoperative anxiety has been shown to correlate to adverse postoperative outcomes. Emotional support could be an effective measure to reduce preoperative anxiety. DESIGN AND METHODS: Patients with planned first coronary artery bypass grafting were randomised into an intervention group (n = 139) and a control group (n = 114). The patients of the control group were routinely informed as usual. The patients of the intervention group received a dialogue with individualised information and emotional support one day before surgery in addition to standard care. This intervention of ~30 minutes was based on a supportive psychotherapy model and was delivered by trained nurses. The primary outcome was the change in anxiety before operation. The secondary outcomes consisted of changes in postoperative anxiety, time on intensive care unit and in-hospital mortality. RESULTS: Significantly reduced anxiety was found in the intervention group patients compared to control patients before coronary artery bypass grafting (p < 0·001) and five days after surgery (p < 0·001). Both groups did not differ in in-hospital mortality and duration of stay in the intensive care unit. CONCLUSIONS: Our short-term psychosocial intervention in patients undergoing coronary artery bypass grafting had a beneficial effect on reducing pre- and postoperative anxiety that was better than routine information alone. RELEVANCE TO CLINICAL PRACTICE: These results advocate training for nurses and physicians to provide emotional support to patients before coronary artery bypass grafting.

Magnetic sensor for arterial distension and blood pressure monitoring.

A novel sensor for measuring arterial distension, pulse and pressure waveform is developed and evaluated. The system consists of a magnetic sensor which is applied and fixed to arterial vessels without any blood vessel constriction, hence avoiding stenosis. The measurement principle could be validated by in vitro experiments on silicone tubes, and by in vivo experiments in an animal model, thereby indicating the non-linear viscoelastic characteristics of real blood vessels. The sensor is capable to provide absolute measurements of the dynamically varying arterial diameter. By calibrating the sensor, a long-term monitoring system for continuously measuring blood pressure and other cardiovascular parameters could be developed based on the method described. This will improve diagnostics for high risk patients and enable a better, specific treatment.

Implantable impedance plethysmography.

We demonstrate by theory, as well as by ex vivo and in vivo measurements that impedance plethysmography, applied extravascularly directly on large arteries, is a viable method for monitoring various cardiovascular parameters, such as blood pressure, with high accuracy. The sensor is designed as an implant to monitor cardiac events and arteriosclerotic progression over the long term.

Anxiety and fear in patients with short waiting times before coronary artery bypass surgery--a qualitative study.

AIMS AND OBJECTIVES: To obtain qualitative information on fears and anxieties of coronary artery bypass grafting patients with short waiting periods (up to a maximum of four weeks) before surgery. BACKGROUND: Coronary artery bypass grafting is a standard procedure in cardiac surgery. However, many patients suffer significant anxiety and fear before the operation. Preoperative anxiety and fear correlate with adverse outcomes, but there is a lack of data on the emotional stressors for patients with short waiting periods as applicable in Germany. This knowledge would be a prerequisite for the development of in-hospital interventions to reduce patients' anxieties and fears. DESIGN: An exploratory study was chosen to learn about patients' anxieties and fears. METHOD: The day before coronary artery bypass grafting, 24 patients were examined with respect to their emotional experience using semi-structured interviews. The results were categorised by inductive content analysis. RESULTS: The overall waiting time for coronary artery bypass grafting was 6 ± 6 days. According to the analysis, the patients' statements were grouped in 'fears', 'negation of fears' and 'other emotional and physical conditions'. The interviews could cover all categories simultaneously. Eighteen patients mentioned fears, and most of them referred to specific issues. However, 16 of the 18 patients also named nonspecific fears and uncertainties. Fifteen patients negated fear. Twenty-three patients described their emotions and/or somatic conditions. CONCLUSIONS: Patients with short waiting periods before coronary artery bypass grafting experience specific as well as nonspecific fears on the day before surgery. In contrast to patients with long waiting (longer than four weeks), uncertainty and frustration about waiting time and feelings of disability are no concerns. RELEVANCE TO CLINICAL PRACTICE: The detailed insight into the emotional experiences of patients with a short waiting time before coronary artery bypass grafting surgery is a basis for targeted anxiety-reducing interventions.

An implantable optical blood pressure sensor based on pulse transit time.

An implantable sensor system for long-term monitoring of blood pressure is realized by taking advantage of the correlation between pulse transit time and blood pressure. The highly integrated implantable sensor module, fabricated using MEMS technologies, uses 8 light emitting diodes (LEDs) and a photodetector on chip level. The sensor is applied to large blood vessels, such as the carotid or femoral arteries, and allows extravascular measurement of highly-resolved photoplethysmograms. In addition, spectrophotometric approaches allow measurement of hemoglobin derivatives. For the calibration of blood pressure measurements, the sensor system has been successfully implemented in animal models.

Subcutaneous blood pressure monitoring with an implantable optical sensor.

We introduce a minimally invasive, implantable system that uses pulse transit time to determine blood pressure. In contrast to previous approaches, the pulse wave is detected by a photoplethysmographic (PPG) signal, acquired with high quality directly on subcutaneous muscle tissue. Electrocardiograms (ECG) were measured with flexible, implantable electrodes on the same tissue. PPG detection is realized by a flat 20 mm x 6 mm optoelectronic pulse oximeter working in reflection mode. The optical sensor as well as the ECG electrodes can be implanted using minimally invasive techniques, with only a small incision into the skin, making long-term monitoring of blood pressure in day-to-day life for high-risk patients possible. The in vivo measurements presented here show that the deviation to intra-arterial reference measurements of the systolic blood pressure in a physiologically relevant range is only 5.5 mmHg, demonstrated for more than 12 000 pulses. This makes the presented sensor a grade B blood pressure monitor.

Early histological changes in the porcine aortic media after thoracic stent-graft implantation.

PURPOSE: To describe the histological findings in the aortic wall 5 days after thoracic endovascular aortic repair (TEVAR) in a porcine model. METHODS: Two overlapping stent-grafts were implanted in each of 6 juvenile pigs, covering the entire descending thoracic aorta (DTA). On the 5(th) postoperative day, tissue samples were taken from the DTA in each animal. Medial thickness and medial necrosis were quantified and compared to measurements from the aortas of 6 control animals. RESULTS: Significant medial thinning was observed in stent-covered regions in the test animals. At the proximal landing zone, aortic wall thickness changed from 1387±68 to 782±74 µm within the covered aortic segment (p = 0.028); at the distal landing site, the wall thickness was 365±67 µm within the stent and 501±57 µm distally (p = 0.028). In the overlap zone, the aortic wall measured 524±122 vs. 1053±77 µm in native controls (p = 0.004). Aortic thickness proximal to the graft did not differ from the proximal region of native aortas (1468±96 vs. 1513±80 µm, p = 0.423), but the aorta was significantly thinner distal to the stent (707±38 vs. 815±52 µm, p = 0.004). Laminar necrosis constituted 38%±7% of the media in the proximal landing zone, 54%±4% in the overlap zone, and 46%±13% in the distal landing zone. CONCLUSION: In this porcine model, significant medial thinning and necrosis of the stented aorta was observed. The findings suggest an early phase of vulnerability of the aortic wall, before scarring and adaptive changes have strengthened the residual aorta.

The Meta-Substituted Isomer of TMPyP Enables More Effective Photodynamic Bacterial Inactivation than Para-TMPyP In Vitro.

Porphyrinoid-based photodynamic inactivation (PDI) provides a promising approach to treating multidrug-resistant infections. However, available agents for PDI still have optimization potential with regard to effectiveness, toxicology, chemical stability, and solubility. The currently available photosensitizer TMPyP is provided with a para substitution pattern (para-TMPyP) of the pyridinium groups and has been demonstrated to be effective for PDI of multidrug-resistant bacteria. To further improve its properties, we synthetized a structural variant of TMPyP with an isomeric substitution pattern in a meta configuration (meta-TMPyP), confirmed the correct structure by crystallographic analysis and performed a characterization with NMR-, UV/Vis-, and IR spectroscopy, photostability, and singlet oxygen generation assay. Meta-TMPyP had a hypochromic shift in absorbance (4 nm) with a 55% higher extinction coefficient and slightly improved photostability (+6.9%) compared to para-TMPyP. Despite these superior molecular properties, singlet oxygen generation was increased by only 5.4%. In contrast, PDI, based on meta-TMPyP, reduced the density of extended spectrum ß-lactamase-producing and fluoroquinolone-resistant Escherichia coli by several orders of magnitude, whereby a sterilizing effect was observed after 48 min of illumination, while para-TMPyP was less effective (p < 0.01). These findings demonstrate that structural modification with meta substitution increases antibacterial properties of TMPyP in PDI.

Polyurethane scaffolds seeded with genetically engineered skeletal myoblasts: a promising tool to regenerate myocardial function.

In animal models, intramyocardial injection of primary skeletal myoblasts is supposed to promote tissue regeneration and to improve cardiac function after myocardial infarction. The usage of genetically engineered myoblasts overexpressing the paracrine factors involved in tissue repair is believed to enhance these effects. However, cell therapy via injection is always accompanied by a high death rate of the injected cells. Here, we describe the construction of a growth factor-producing myoblast-seeded scaffold to overcome this limitation. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were seeded on polyurethane (PU) scaffolds (Artelon) and transfected with DNA of VEGF-A, HGF, SDF-1, or Akt1 using the lipid-based Metafectene Pro method. Overexpression was verified by ELISA, RT-PCR (VEGF-A, HGF, and SDF-1) and Western blot analysis (Akt1). The seeded scaffolds were transplanted onto damaged myocardium of Lewis rats 2 weeks after myocardial infarction. Six weeks later, their therapeutic potential in vivo was analyzed by measurement of infarction size and capillary density. Primary rat skeletal myoblasts seeded on PU scaffolds were efficiently transfected, achieving transfection rates of 20%. In vitro, we noted a significant increase in expression of VEGF-A, HGF, SDF-1, and Akt1 after transfection. In vivo, transplantation of growth factor-producing myoblast-seeded scaffolds resulted in enhanced angiogenesis (VEGF-A, HGF, and Akt1) or a reduced infarction zone (SDF-1 and Akt1) in the ischemically damaged myocardium. In summary, we constructed a growth factor-producing myoblast-seeded scaffold which combines the beneficial potential of stem cell transplantation with the promising effects of gene-therapeutic approaches. Because this matrix also allows us to circumvent previous cell application drawbacks, it may represent a promising tool for tissue regeneration and the re-establishment of cardiac function after myocardial infarction.

Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease.

OBJECTIVE: Outcomes after ventricular assist device (VAD) implantation have significantly improved during the last decade. However, bleeding episodes remain a serious complication of VAD support. This cannot be explained by the individual anticoagulation regimen alone in several cases, but may be symptomatic of acquired von Willebrand disease (VWD). The leading finding in acquired VWD (AVWD) is the loss of large multimers which results in diminished binding to collagen and to the platelets. We, therefore, analysed patients with two VAD types for laboratory parameters of VWD and compared them with patients after heart transplantation (HTX). MATERIALS AND METHODS: Seven patients with a HeartMate II left-ventricular assist device and five patients who received a Thoratec biventricular assist device were included in this study. Eight HTX recipients served as controls. Analysis included international normalized ratio (INR), partial thromboplastin time (PTT), platelet count, von Willebrand factor (VWF) antigen, collagen binding capacity, ristocetin cofactor activity, the ratios of the latter two to the VWF antigen and presence of large VWF multimers. RESULTS: The VAD and HTX groups did not differ with regard to age or time-point of analysis after surgery. INR and number of platelets were comparable in both groups, PTT was prolonged in VAD patients. Both VAD and HTX patients had elevated but comparable amounts of VWF antigen. However, large multimers were missing in all of 10 tested VAD patients. In contrast, five of six tested HTX recipients displayed normal multimer pattern. Indeed, collagen binding capacity and ristocetin cofactor activity (which measures binding of VWF to platelets) were lower in VAD patients compared to HTX recipients. Impaired coagulation associated with VADs was also reflected by the diminished ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. A pathologic collagen binding ratio was found in all 10 tested VAD patients and one of the eight HTX patients, a reduced ristocetin cofactor activity ratio in 10 of 12 VAD and one of eight HTX patients. CONCLUSION: Non-surgical postoperative bleeding after VAD implantation could be explained by an AVWD. Several pharmacologic treatment options (tranexamic acid, desmopressin, VWF-factor VIII concentrate, recombinant factor VIIa) may arise from our data. Improved VAD design could prevent this problem in the future.

Platelet Secretion Defects and Acquired von Willebrand Syndrome in Patients With Ventricular Assist Devices.

BACKGROUND: The number of implanted ventricular assist devices (VADs) has increased significantly recently. Bleeding, the most frequent complication, cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD featuring potential improvements over the HeartMate II. METHODS AND RESULTS: In this study, we investigated the prevalence and onset of AVWS in 198 VAD patients. To our knowledge, this is the largest cohort of VAD patients whose longitudinal data on AVWS have been collected. We also analyzed whether AVWS is less severe in HM III patients than in HeartMate II patients. Because platelet dysfunction can raise the bleeding risk, we investigated platelet function in a subset of patients. In total, 198 VAD patients and 60 patients with heart transplants as controls were included in this study. The ratio of von Willebrand factor collagen binding capacity to von Willebrand factor:antigen, multimer analyses, and platelet function (especially secretion of α- and δ-granules) were investigated. All 198 VAD patients developed AVWS. As soon as the VAD was explanted, the AVWS disappeared within hours. AVWS was less severe in the HM III patients than in the HeartMate II patients. The HM III patients had fewer bleeding symptoms. In addition, VAD patients exhibited a platelet α- and δ-granule secretion defect. CONCLUSIONS: AVWS develops in VAD patients and may increase the bleeding risk. The HM III device causes less severe AVWS. Platelet secretion defects should be investigated in VAD patients because they also raise the bleeding risk. CLINICAL TRIAL REGISTRATION: https://www.drks.de/drks_web. Unique identifier: DRKS00000649.