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 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.

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.

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.

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.

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.

Moderate ischemic mitral regurgitation: coronary artery bypass grafting with versus without simultaneous treatment of the mitral valve.

BACKGROUND: Ischemic mitral regurgitation (IMR) is a frequent complication of coronary artery heart disease and is associated with increased mortality. Controversies exists whether patients with moderate IMR may benefit from a combined procedure with coronary artery bypass grafting (CABG) and treatment of mitral regurgitation. METHODS: 451 patients with moderate IMR (grade 2) receiving either CABG alone (CABG only) or additional mitral valve repair or replacement (CABG+MV) were included in this observational single-centre study. Patients were matched according to the number of bypass grafts, preoperative NYHA functional class and age. In total, 42 patients (21 CABG only, 21 CABG+MV) were analysed. RESULTS: The mean follow-up was 4.3±1.9 years. CABG alone reduced the IMR grade to 1.2±0.5, whereas the combined procedure resulted in a decrease to 0.6±0.7 (P=0.039). NYHA functional class was reduced from grade 2.8±0.6 to 1.6±0.5 (CABG only) and 2.0±1.1 (CABG+MV, P=0.55). Three- and five-year survival rates were 71% and 53% in the CABG only group compared to 60% both after 3 and 5 years in the CABG+MV group (P=0.89). CONCLUSIONS: In this observational study, combined CABG and surgical treatment of moderate IMR was associated with a more effective reduction of IMR than CABG alone. No statistically significant differences in survival or NYHA functional class were observed. Further studies will need to investigate the value of additional mitral valve surgery in moderate IMR.

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.

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.

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.

Proteomics highlights decrease of matricellular proteins in left ventricular assist device therapy†.

OBJECTIVES: We investigated the impact of mechanical unloading with a left ventricular assist device (LVAD) on the myocardial proteome. METHODS: We collected 11 patient-matched samples of myocardial left ventricular tissue of patients with non-ischaemic dilate cardiomyopathy, harvested at time of LVAD implant ('pre-LVAD') and heart transplant ('post-LVAD'). Samples were studied by quantitative proteomics. Further we performed histological assessment of deposited collagens and immune infiltration in both pre- and post-LVAD samples. RESULTS: A core set of >1700 proteins was identified and quantified at a false discovery rate <1%. The previously established decrease post-LVAD of alpha-1-antichymotrypsin was corroborated. We noted a post-LVAD decrease of matricellular proteins and proteoglycans such as periostin and versican. Also, proteins of the complement system and precursors of cardiac peptide hormones were decreased post-LVAD. An increase post-LVAD was evident for individual proteins linked to the innate immune response, proteins involved in diverse metabolic pathways, and proteins involved in protein synthesis. Histological analysis did not reveal significant alterations post-LVAD of deposited collagens or immune infiltration. The proteomic data further highlighted a pronounced inter-patient heterogeneity with regards to the impact of LVAD therapy on the left ventricular myocardial proteome. Finally, the proteomic data showed differential proteolytic processing in response to LVAD therapy. CONCLUSIONS: Our findings underline a strong impact of LVAD therapy on the left ventricular myocardial proteome. Together with previous studies, protein markers of LVAD therapy such as alpha-1-antichymotrypsin are becoming apparent. Further, matricellular proteins are emerging as important components in response to LVAD therapy.

Acquired Von Willebrand syndrome in patients on long-term support with HeartMate II.

Objectives: Impaired binding of Von Willebrand factor (VWF) to platelets and to collagen due to acquired Von Willebrand syndrome (AVWS) is associated with support from a ventricular assist device (VAD) and can contribute to bleeding tendencies in patients with VADs. The onset of AVWS has been shown to occur immediately after VAD implantation. Our aim was to determine long-term data on AVWS in VAD patients. Methods: We analysed 278 data sets of 74 patients on HeartMate II (HMII) support for 3-80 months after implantation (11.2 ± 12.1, median 6.3 months.). Ristocetin cofactor activity (VWF:RCo), collagen binding capacity (VWF:CB), VWF antigen (VWF:Ag) and the ratios of VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag were determined. Further, the presence of high molecular weight (HMW) multimers of VWF was investigated. Results: Abnormally low values of VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag were found in 69% and 97% of blood samples, respectively. Only ten of 181 multimer analyses showed a normal pattern, and HMW multimers were present in both specimens in only one of the 74 patients. No significant changes in these parameters were observed over time. The VWF:CB/VWF:Ag ratio correlated with the multimer patterns, whereas the VWF:RCo/VWF:Ag ratio seemed to be less sensitive for AVWS. Conclusions: Our data indicate that AVWS is a typical phenomenon in patients with VAD support and that there are no time-dependent changes in these parameters apparent in most patients on long-term support with HMII.

Characterization of serum matrix metalloproteinase 2/9 levels in patients with ascending aortic aneurysms.

OBJECTIVES: The objectives of this study were to identify interrelations between matrix metalloproteinase-2 (MMP2)/MMP9 levels and clinical variables in patients with aortic root/ascending aortic aneurysms and to describe comorbidities as possible biasing factors in the widely discussed correlation of serum MMP levels and aortic diameter. METHODS: Serum MMP9 and MMP2 levels were quantified in 32 consecutive patients with ascending aortic and/or aortic root aneurysms (>45 mm) at the Heart Center University of Freiburg from May 2013 to January 2014. The influence of comorbidities and medication on serum MMP2 and MMP9 levels was studied. We took into account ascending aortic diameter (aAD), aortic valve configuration, hypertension, age and hyperlipidaemia as factors possibly altering serum MMP levels. The relation between serum MMP levels and aAD was examined by a correlation test based on ranks. RESULTS: Serum MMP2 levels and aAD correlated positively. Correlation was increased in patients without hyperlipidaemia (Spearman's ρ = 0.62, P = 0.008 in patients without hyperlipidaemia; ρ = 0.409, P = 0.020 in all patients). Serum MMP9 levels did not correlate with aAD and showed greater variation. Serum MMP9 levels were significantly associated with hyperlipidaemia (P = 0.037). CONCLUSIONS: The distinct correlation patterns in patients with and without hyperlipidaemia have to be considered when defining the potential of MMP2 as a biomarker in future studies. The relation between MMP9 and hyperlipidaemia has to be further investigated.

MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms.

OBJECTIVE: The need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress. METHODS: Serum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair. RESULTS: Pro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue-and serum MMP-2 isoforms, nor any indication that pro-MMP-2 functions as a common marker of high aortic wall stress.

Photonic sensing of arterial distension.

Most cardiovascular diseases, such as arteriosclerosis and hypertension, are directly linked to pathological changes in hemodynamics, i.e. the complex coupling of blood pressure, blood flow and arterial distension. To improve the current understanding of cardiovascular diseases and pave the way for novel cardiovascular diagnostics, innovative tools are required that measure pressure, flow, and distension waveforms with yet unattained spatiotemporal resolution. In this context, miniaturized implantable solutions for continuously measuring these parameters over the long-term are of particular interest. We present here an implantable photonic sensor system capable of sensing arterial wall movements of a few hundred microns in vivo with sub-micron resolution, a precision in the micrometer range and a temporal resolution of 10 kHz. The photonic measurement principle is based on transmission photoplethysmography with stretchable optoelectronic sensors applied directly to large systemic arteries. The presented photonic sensor system expands the toolbox of cardiovascular measurement techniques and makes these key vital parameters continuously accessible over the long-term. In the near term, this new approach offers a tool for clinical research, and as a perspective, a continuous long-term monitoring system that enables novel diagnostic methods in arteriosclerosis and hypertension research that follow the trend in quantifying cardiovascular diseases by measuring arterial stiffness and more generally analyzing pulse contours.

Preserved brain morphology after controlled automated reperfusion of the whole body following normothermic circulatory arrest time of up to 20 minutes.

OBJECTIVES: Clinical outcomes following cardiac arrest (CA) and resuscitation remain a cause for concern. The use of Controlled Automated Reperfusion of the whoLe body (CARL) confers superior neurological outcome even after extended periods of CA. We aimed at investigating clinical outcome and brain morphology preservation when employing CARL following CA periods of 20 min. METHODS: Twenty-eight pigs were allocated to four extracorporeal circulation treatment strategies; seven others served as magnetic resonance imaging (MRI) controls. In prompt cardiopulmonary resuscitation (CPR; n = 6), induced circulatory arrest was followed immediately by open cardiac massage of 15 min, thereafter by CARL for 60 min. In delayed CPR (n = 6), induced CA was maintained for 15 min, after that open cardiac massage of 10 min duration was performed prior to extracorporeal CPR (ECPR) of 60 min. Induced CA times of 15 min in the ECPR 15' group (n = 6) and CA of 20 min in the CARL 20' group (n = 10) were followed by ECPR of 60 min and CARL of 60 min, respectively, without prior CPR. Daily neurological deficit scoring (NDS) up to the seventh day, markers of cellular injury [alanine transaminase (ALT), aspartate transaminase (AST) and neuron-specific enolase (NSE)] and brain MRI were performed. RESULTS: 100% survival and normal NDSs were achieved in all animals in the prompt CPR and ECPR 15' groups. In CARL 20', nine animals survived. In contrast, only one animal in the delayed CPR group survived; three animals died within 24 h with a further two dying on Days 4 and 5, respectively. All markers of cellular injury were elevated in the delayed CPR group, ALT [38 (20.3) to 206 U/l (158.2); P = 0.0095], AST [26 (18.8) to 97 U/l (1965.8); P = 0.0095] and NSE [0.45 (0.25) to 7.95 µg/l (24.03); P = 0.0095]. In the ECPR 15' group, only NSE [0.45 (0.15) to 1.20 µg/l (2.40); P = 0.0065] remained elevated. In the CARL 20' group, differences in ALT [36 (10) to 53 U/l (20); P = 0.0005] and NSE [0.50 (0.40) to 1.5 µg/l (0.40); P < 0.0001] values were evident. T2-weighted MR images of the cerebellum [454 (28) to 495 mm2/s (55); U = 11; P = 0.0311], caudate nucleus [400 (59) to 467 mm2/s (42); U = 9; P = 0.0156], lentiform nucleus [377 (89) to 416 mm2/s (55); U = 11; P = 0.0311] and hippocampus [421 (109) to 511 mm2/s (58); U = 9; P = 0.0164] in the CARL 20' group showed higher signal intensities compared with controls. In delayed CPR, corresponding regions of interest on early apparent diffusion coefficient images showed a restricted diffusion. CONCLUSIONS: In our experimental animal model of CA, CARL results in satisfactory survival at CA periods of 20 min despite detected enzyme and morphological changes. These changes did not translate to clinical neurological deficits.

Mental health status of patients with mechanical aortic valves, with ventricular assist devices and after heart transplantation.

OBJECTIVES: Mental health is a complex construct, in which emotional aspects and quality of life are central. It has been assessed in patients after heart transplantation (HTX) and occasionally in those with ventricular assist devices (VADs). However, there are no studies that compare patients with primary HTX with those with HTX ending VAD support. Evidence for patients with mechanical aortic valve replacement is also limited. We compared mental outcome for these four groups for the first time. We also focused on the question of an artificial device, i.e. VAD or mechanical aortic valve, as distinct from a biological graft, i.e. HTX. METHODS: Two questionnaires were applied: The Hospital Anxiety and Depression Scale, the German version consists of two subscales for anxiety and for depression, and the 12-item Short Form Health Survey, the German version contains two subscales for physical and for mental performance measuring quality of life. We included 46 patients with mechanical aortic valve replacement, 55 after HTX and 22 on support by a long-term VAD. The HTX group consisted of 38 patients with primary HTX and 17 recipients who were on VAD support before transplantation. The index operation was at least 6 months ago. RESULTS: HTX patients suffered less from anxiety and depression than patients with mechanical aortic valve replacement or those on VAD. HTX patients had higher scores on the physical scale but not on the mental component scale of the 12-item Short Form Health Survey compared with VAD patients. Conversely, patients with mechanical aortic valve replacement did worse with regard to mental but not physical performance compared with HTX patients. VAD and mechanical aortic valve replacement patients differed only with regard to physical condition, but not with regard to anxiety, depression and mental status. HTX patients with and without VAD support before transplantation achieved similar values on all scales. Mental scales did not correlate with age or time after surgery. CONCLUSIONS: HTX patients had the best outcome compared with the other groups with respect to mental health. Mechanical aortic valve replacement patients did not differ from VAD patients with respect to anxiety, depression and mental quality of life scores. Mechanical aortic valve replacement patients might be more in need of psychological support than expected. Further, VAD patients who undergo HTX reach similar mental and physical results when compared with patients with primary HTX, i.e. they seem to cope well in the long run.

Genetic variations of phenprocoumon metabolism in patients with ventricular assist devices.

OBJECTIVES: Anticoagulation in patients with ventricular assist device (VAD) support is crucial and to date, no alternative to vitamin K antagonists (VKAs) can be safely used. Genetic variances of cytochrome p450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC) have been recently connected with variation of VKA maintenance as well as loading doses. In this retrospective study, we assessed the incidence of genetic variations and the influence of different genotypes of CYP2C9 and VKORC1 in VAD patients. METHODS: A total of 161 patients received a VAD implant in our institution between January 2006 and July 2014. Of these, 63 consented to genetic analysis and completed an interview with standardized questions on phenprocoumon (PC) dosage, international normalized ratio and anticoagulation-related complications. Determination of VKORC (-1639 G > A; -1173 C > T) and of CYP2C9 (*2, 430 C > T; *3, 1075 A > C) polymorphisms was performed by polymerase chain reaction and restriction analysis. RESULTS: The most common VKORC-1639 allele combination was wild-type GG (41%) followed by GA (32%) and AA (27%). Patients with VKORC1 polymorphisms AA and GA needed less PC in the maintenance phase of anticoagulation (P < 0.001) compared with wild-type GG patients. In contrast, CYP2C9 polymorphisms showed no effect on PC doses. Similar findings were observed in the initiation phase of PC therapy. High complications rates under PC therapy were observed particularly at the beginning. CONCLUSIONS: VKORC polymorphism affects PC dosage in the initiation as well as the maintenance phase. High rates of bleeding complications and thromboembolic events were found at the beginning of PC therapy in VAD patients. Therefore, a genotype-guided dosage algorithm might be useful in VAD patients.

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.