Summary Background Remote ischaemic preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and ...efficacy of this procedure. Methods Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov , number NCT01406678. Findings 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237–298) in the remote ischaemic preconditioning group and 321 ng/mL (287–360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70–0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66–0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic preconditioning than without (ratio 0·27, 95% CI 0·08–0·98, p=0·046). Interpretation Remote ischaemic preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. Funding German Research Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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This work analyzes the feasibility of integrating a modified commercial Capstone C30 microturbine unit into a non‐nuclear testbed developed for performance evaluation of microreactor design ...concepts. Testing will be conducted to provide detailed reactor core and heat removal section thermal hydraulic performance data for prototypical geometries and operating conditions and demonstrate integration with relevant power conversion units. The modified C30 power conversion unit (PCU) uses external electrical heating, rather than fossil fuel combustion, to provide a maximum power output of ~30 kWe in a closed Brayton cycle (CBC) loop using nitrogen as the working fluid. A 75 kWt electrically heated test article was evaluated as the heat source to provide a turbine inlet temperature of 600°C to the modified C30 PCU. The operation of a test article supplying a maximum thermal power of 250 kWt was also considered. The analyses performed here indicate that the CBC PCU will be capable of operating over a range of steady state and transient conditions to evaluate test article heat transfer performance in representative operational scenarios. Normal, off‐design operation and dynamic stability of the PCU are analyzed, and a proposed set of tests of the power control schemes and heat source‐PCU coupling are outlined. This study supports the timely development of microreactors intended for deployment by the end of this decade.
This work analyzes the feasibility of integrating a modified commercial Capstone C30 microturbine unit into a non‐nuclear testbed developed for performance evaluation of microreactor design concepts. The modified C30 uses external electrical heating, rather than combustion, to provide a maximum power output of ~30 kWe in a closed Brayton cycle loop using nitrogen as the working fluid. A 75 kWt test article was evaluated as the heat source to provide a turbine inlet temperature of 600°C.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Extracorporeal cytokine adsorption is an option in septic shock as an additional measure to treat a pathological immune response. Purpose of this study was to investigate the effects of ...extracorporeal cytokine adsorption on hemodynamic parameters in patients with acute kidney injury (AKI) on continuous renal replacement therapy (CRRT) and septic shock after cardiac surgery.
In this retrospective study, a total of 98 patients were evaluated. Hemoadsorption was performed by the CytoSorb® adsorber. In all patients cytokine adsorption was applied for at least 15 hours and at least one adsorber was used per patient. To compare cumulative inotrope need in order to maintain a mean arterial pressure (MAP) of ≥ 65 mmHg, we applied vasoactive score (VAS) for each patient before and after cytokine adsorption. A paired t-test has been performed to determine statistical significance.
Before cytokine adsorption the mean VAS was 56.7 points. This was statistically significant decreased after cytokine adsorption (27.7 points, p< 0.0001). Before cytokine adsorption, the mean noradrenalin dose to reach a MAP of ≥ 65 mmHg was 0.49 μg/kg bw/min, the mean adrenalin dose was 0.12 μg/kg bw/min. After cytokine adsorption, significantly reduced catecholamine doses were necessary to maintain a MAP of ≥ 65 mmHg (0.24 μg/kg bw/min noradrenalin; p< 0.0001 and 0.07 μg/kg bw/min adrenalin; p < 0.0001). Moreover, there was a significant reduction of serum lactate levels after treatment (p< 0.0001). The mean SOFA-score for these patients with septic shock and AKI before cytokine adsorption was 16.7 points, the mean APACHE II-score was 30.2 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.7 points was 77,0%, respectively 73,0% on APACHE II-score, while the all-cause in-hospital mortality rate of the patients in this study was 59.2%.
In patients with septic shock and AKI undergoing cardiac surgery, extracorporeal cytokine adsorption could significantly lower the need for postoperative inotropes. Additionally, observed versus SOFA- and APACHE II-score predicted in-hospital mortality rate was decreased.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type ...natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH.
Background Major scores for the evaluation of procedural risk in cardiac surgery are the European system for cardiac operative risk evaluation score (EuroSCORE), the Society of Thoracic Surgeons ...(STS) score, and the Parsonnet score. The aim of our study was to analyze the predictive value of these scores in “high risk” patients undergoing isolated aortic valve replacement (AVR). Methods Six hundred and fifty-two patients underwent isolated AVR from January 1999 through June 2007. Emergency and redo operations were included; acute endocarditis was excluded. Evaluation was performed by logistic regression analysis. Data collection was prospective. Results The mean logistic EuroSCORE of all patients was 8.5 ± 7.9%, the mean STS score was 4.4 ± 3.9%, and the mean logistic Parsonnet score was 9.8 ± 8.5%. In-hospital mortality was 2.5% (n = 16). Freedom from all-cause death was 93.4% at 1 year, 90.2% at 2 years, and 75.8% at 5 years, respectively. A total of 182 patients had a logistic EuroSCORE greater than 10. For the group of patients with a EuroSCORE between 10% and 20% (n = 130) the mean EuroSCORE was 13.9 ± 2.8% and the STS score was 6.5 ± 3.8%. Observed mortality was 4.6% in this group. For the 52 patients with a logistic EuroSCORE of at least 20 (mean 28.5 ± 10.3%, STS score 10.1 ± 7.3%) the observed mortality was 3.9% (n = 2). By stepwise logistic regression, none of the EuroSCORE variables could be identified as an independent predictor in the “high- risk” group. Conclusions The logistic EuroSCORE was primarily created to allow patient grouping for the total spectrum of cardiac surgery. In patients undergoing isolated AVR, the EuroSCORE highly overestimates mortality, whereas the STS score seems to be actually more suitable in assessing perioperative mortality for these patients.
We evaluated the influence of transit-time flow measurement with epicardial and epiaortic high-frequency ultrasound in patients undergoing coronary artery bypass grafting procedure.
The Registry for ...Quality Assessment with Ultrasound Imaging and Transit-time Flow Measurement in Cardiac Bypass Surgery study is a multicenter, prospective study among 7 international centers performing coronary artery bypass grafting procedures. The primary end point was any change in the planned surgical procedure. Major secondary end points consisted of the rate and reason for surgical changes related to the aorta, in situ conduits, coronary targets, and completed grafts, and the rate of in-hospital mortality and major morbidity.
Between April 2015 and December 2017, 1046 patients were enrolled. Of those, 1016 were included in the final analyses. Mean age was 65.9 years, 14.0% were women, and diabetes was present in 39.6%. Off-pump procedures were performed in 39.6% and bilateral internal thoracic arteries in 30.5%. The primary end point occurred in 25.2% of patients (n = 256) and in 77% (197 out of 256) this was based on transit-time flow measurement and/or high-frequency ultrasound. Surgical changes were related to the aorta in 9.9%, to in situ conduits in 2.7%, and the coronary targets in 22.6%. Graft revision occurred in 7.8%, including revisions of the proximal and/or distal anastomosis in 6.6%. In-hospital adverse event rates were 0.6% for mortality, 1.0% for cerebrovascular events, and 0.3% for myocardial infarction.
Surgical changes related to the aorta, conduits, coronary targets, and anastomosis were made in 25% of patients. This was associated with low operative mortality and low major morbidity. Transit-time flow measurement and high-frequency ultrasound may improve the quality, safety, and efficacy of coronary artery bypass grafting procedures and should be considered as a routine procedural aspect.
Changes to the planned surgical strategy were made in 25.2% of cases with few complications. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Postoperative sepsis is an important cause of morbidity and mortality in patients with infective endocarditis undergoing surgical therapy. Blood purification using hemoadsorption therapy shows ...promising results in the treatment of sepsis. In this study, the clinical effects of intraoperative hemoadsorption in high-risk patients with infective endocarditis were evaluated. Eligible candidates were high-risk patients with infective endocarditis undergoing cardiac surgery between January 2014 and December 2019. Patients with intraoperative hemoadsorption (hemoadsorption) were compared to patients without hemoadsorption (control). The endpoints were the incidence of postoperative sepsis, sepsis-associated death and in-hospital mortality. Additionally, postoperative vasopressor need, systemic vascular resistance indices and Sequential Organ Failure Assessment (SOFA) scores were compared. After propensity score matching, 70 high-risk patients were included. Postoperative sepsis occurred in 14 patients in the hemoadsorption group and in 16 patients in the control group, p = 0.629. Four patients died due to postoperative sepsis in the hemoadsorption group, while 11 postoperative septic patients died in the control group, p = 0.041. In-hospital mortality was 34% in the hemoadsorption group versus 43% in the control group, p = 0.461. On ICU-admission and the first postoperative day, the cumulative vasopressor need was 0.17 versus 0.25 mug/kgBW/min, p = 0.123 and 0.06 versus 0.11 mug/kgBW/min, p = 0.037, and the systemic vascular resistance index was 1448 versus 941 dyn·s·cm.sup.-5, p = 0.013 and 1156 versus 858 dyn·s·cm.sup.-5, p = 0.110 in the hemoadsorption versus control group, respectively. Postoperative course of SOFA score normalized significantly (p = 0.01) faster in the hemoadsorption group. In high-risk cardiac surgical patients with infective endocarditis, intraoperative hemoadsorption significantly reduced sepsis-associated mortality. Furthermore, intraoperative hemoadsorption resulted in significant faster recovery of hemodynamics and organ function. Intraoperative hemoadsorption seems to attenuate the severity of postoperative sepsis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prioritizing genes for translation to therapeutics for common diseases has been challenging. Here, we propose an approach to identify drug targets with high probability of success by focusing on ...genes with both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). We find 98 BEST genes for a variety of indications. Drugs targeting those genes are 3.8-fold more likely to be approved than non-BEST genes. We focus on five genes (IGF1R, NPPC, NPR2, FGFR3, and SHOX) with evidence for bidirectional effects on stature. Rare protein-altering variants in those genes result in significantly increased risk for idiopathic short stature (ISS) (OR = 2.75, p = 3.99 × 10
). Finally, using functional experiments, we demonstrate that adding an exogenous CNP analog (encoded by NPPC) rescues the phenotype, thus validating its potential as a therapeutic treatment for ISS. Our results show the value of looking for bidirectional effects to identify and validate drug targets.
A model was developed to estimate the process energy requirements of a switchable polarity solvent forward osmosis (SPS FO) system for water purification from aqueous NaCl feed solution ...concentrations ranging from 0.5 to 4.0molal at an operational scale of 480m3/day (feed stream). The model indicates recovering approximately 90% of the water from a feed solution with NaCl concentration similar to seawater using SPS FO would have total equivalent energy requirements between 2.4 and 4.3kWh per m3 of purified water product. The process is predicted to be competitive with current costs for disposal/treatment of produced water from oil and gas drilling operations. Once scaled up the SPS FO process may be a thermally driven desalination process that can compete with the cost of seawater reverse osmosis.
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•Concentration dependent SPS FO water treatment processes energy model.•SPS FO process modeled with and without geothermal energy contributions.•SPS FO found to be economically viable over a wide range of concentrations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Transcatheter methods have been rapidly evolving to provide an alternative less invasive therapeutic option, mainly because redo patients often present with multiple comorbidities and high operative ...risk. We sought to evaluate and compare our experience with transapical transcatheter mitral valve replacement (TA-TMVR) to conventional redo mitral valve replacement in patients presenting with degenerated biological mitral valve prostheses or failed valve annuloplasty.
Between March 2012 and November 2020, 74 consecutive high-risk patients underwent surgical redo mitral valve replacement (n = 33) or TA-TMVR (n = 41) at our institution. All patients presented with a history of a surgical mitral valve procedure. All transcatheter procedures were performed using the SAPIEN XT/3™ prostheses. Data collection was prospectively according to MVARC criteria.
The mean logistic EuroSCORE-II of the whole cohort was 19.9±16.7%, and the median STS-score was 11.1±12.5%. The mean age in the SMVR group was 63.7±12.8 years and in the TMVR group 73.6±9.7 years. Patients undergoing TA-TMVR presented with significantly higher risk scores. Echocardiography at follow up showed no obstruction of the left ventricular outflow tract, no paravalvular leakage and excellent transvalvular gradients in both groups (3.9±1.2 mmHg and 4.2±0.8 mmHg in the surgical and transcatheter arm respectively). There was no difference in postoperative major adverse events between the groups with no strokes in the whole cohort. Both methods showed similar survival rates at one year and a 30-day mortality of 15.2% and 9.8% in SAVR and TMVR group, respectively. Despite using contrast dye in the transcatheter group, the rate of postoperative acute kidney failure was similar between the groups.
Despite several contraindications for surgery, we showed the non-inferiority of TA-TMVR compared to conventional surgical redo procedures in high-risk patients. With its excellent hemodynamic and similar survival rate, TA-TMVR offers a feasible alternative to the conventional surgical redo procedure in selected patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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