Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry.

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.

Impact of aortic root geometry and degree of aortic calcification on outcomes of patients undergoing TAVI procedure.

AIMS: Adequate differentiation of calcifications in contrast-enhanced CT scans remains difficult to assess TAVI parameters. The size of the aortic leaflets has not been taken into account so far in present studies. The aim of our study was to establish a new method for optimized quantification of the aortic valve calcification degree in contrast-enhanced CT scans for better preoperative prediction of postoperative paravalvular leak after TAVI. METHODS AND RESULTS: We retrospectively analyzed preoperative contrast-enhanced CT scans of patients who underwent TAVI in our institution between 2014 and 2017. Calcium volume was quantified by a method using contrast enhanced computer tomography (3mensio-Structural Heart-7.2 software) with different iodine contents for better discrimination of contrast agent from calcium and by an individually set Houndsfield Unit (HU) threshold with 50HU above the individually determined reference value. Calcium volume was correlated with surface area of each aortic cusp. Perioperative variables were analyzed. All patients (n = 150) with severe aortic stenosis were treated with TAVI implantation. Overall incidence of postoperative trace to moderate PVL was 37%. The amount of calcium correlated with the incidence of PVL. In a logistic regression analysis total volume of calcification (p = .032) as well as calcification of each aortic cusp (NC_p = .001; RC_p < .001; LC_p = .001) were independent predictors. CONCLUSIONS: Calcification degree as well as its correlation with the surface area of each aortic cusp significantly influence incidence of PVL. Our new method improves preoperative quantification of the calcification degree by use of contrast agents with different iodine contents and thereby helps to improve patients' outcomes.

Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS).

INTRODUCTION: The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest. METHODS: This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis. RESULTS: The trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250). CONCLUSIONS: MiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain.

A novel pulsatile blood pump design for cardiothoracic surgery: Proof-of-concept in a mock circulation.

BACKGROUND: Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. The present study investigated the properties of a novel positive displacement blood pump in a mock circulation. METHODS: The pump was attached to an aortic model with a human-like geometry and compliance as a pseudo patient. Hemodynamic data were recorded while the pump settings were adjusted systematically. RESULTS: Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mm Hg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mm Hg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F = 40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mm Hg and F = 40 bpm. At F = 40 bpm, PP was 58.7 mm Hg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings. CONCLUSIONS: The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications are planned to establish this concept for adult pulsatile perfusion.

Improving adult pulsatile minimal invasive extracorporeal circulation in a mock circulation.

BACKGROUND: Pulsatile extracorporeal circulation (ECC) may improve perfusion of critical organs during cardiac surgery. This study analyzed the influence of the components of a minimal invasive ECC (MiECC) on the transfer of pulsatile energy into the pseudo-patient of a mock circulation. METHODS: An aortic model with human-like geometry and compliance was perfused by a diagonal pump. Surplus hemodynamic energy (SHE) was determined from flow and pressure data. Five adult-size oxygenator models and three sizes of cannulas were compared. Pulsatile pump settings were optimized, and parallel dual-pump configurations were evaluated. RESULTS: Oxygenator models showed up to twofold differences in pressure gradients and influenced SHE at flow rates up to 2.0 L min-1 . Adjustments of frequency, systole duration, and rotational speed gain significantly improved SHE compared with empirical settings, with SHE above 21% of mean arterial pressure at flow rates of 1.0 L min-1 to 1.5 L min-1 and SHE above 5% at 3.5 L min-1 . Small diameter cannula (15 Fr) limited SHE compared with larger cannula (21 Fr and 23 Fr). Two diagonal pumps did not provide higher SHE than a single pump, but permitted additional control over pulse pressure and SHE by varying the total fraction of pulsatile flow and the fraction of flow bypassing the oxygenator. CONCLUSIONS: Proper selection of components and optimizations of pump settings significantly improved pulse pressure and SHE of pulsatile MiECC. Surplus hemodynamic energy depended on flow rate with a maximum at 1.0 L min-1 -1.5 L min-1 . Pulsatile MiECC may specifically assist organ perfusion during phases of low flow.

2021 MiECTiS focused update on the 2016 position paper for the use of minimal invasive extracorporeal circulation in cardiac surgery.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

Preservation of Adrenoceptor and Endothelin Receptor Mediated Vasoconstriction and of Endothelium-Dependent Relaxation after Cold Storage of Explanted Blood Vessels for ex vivo Analyses.

INTRODUCTION: Adrenoceptor and endothelin (ET) receptor-mediated vasoconstriction as well as endothelium-dependent vasodilation of human saphenous veins were compared before and after 20 h of cold storage. METHODS: Contractile responses to potassium chloride (KCl), norepinephrine (NE), and ET-1 as well as vasodilator responses to acetylcholine (ACh) were evaluated. RESULTS: Storage in HEPES-supplemented Dulbecco's modified Eagle's medium (HDMEM) diminished KCl induced contractile forces to 71% (p = 0.002) and NE induced contractions to 80% (p = 0.037), in contrast to HEPES-supplemented Krebs-Henseleit solution (HKH) and TiProtec solution. KCl-normalized NE contractions were not affected by storage. NE EC50 values were slightly lower (7.1E-8 vs. 7.5E-8, p = 0.019) after storage in HKH, with no changes after storage in the other solutions. Endothelium-dependent responses to ACh were not affected by storage. ET-1 induced contractions were attenuated after storage in HDMEM (77%, p = 0.002), HKH (75%, p = 0.020), and TiProtec (73%, p = 0.010) with no changes in normalized constrictions. ET-1 EC50 values were not affected by storage. CONCLUSION: Loss of contractility after storage in HDMEM may reflect the lower content of dextrose. There was no specific attenuation of adrenoceptor, ET-receptor, or ACh receptor mediated signal transduction after storage in any of the media. HKH or TiProtec are equally suitable cold storage solutions for ex vivo measurements.

Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity.

In this study, we characterize age-related phenotypes of human hematopoietic stem cells (HSC). We report increased frequencies of HSC, hematopoietic progenitor cells and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSC further exhibited a delay in initiating division ex vivo though without changes in their division kinetics. The activity of the small RhoGTPase Cdc42 was elevated in aged human hematopoietic cells and we identified a positive correlation between Cdc42 activity and the frequency of HSC upon aging. The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarization of aged human HSC with respect to Cdc42. Elevated activity of Cdc42 in aged HSC thus contributed to age-related changes in HSC. Xenotransplant, using NBSGW mice as recipients, showed elevated chimerism in recipients of aged compared to young HSC. Aged HSC treated with CASIN ex vivo displayed an engraftment profile similar to recipients of young HSC. Taken together, our work reveals strong evidence for a role of elevated Cdc42 activity in driving aging of human HSC, and similar to mice, this presents a likely possibility for attenuation of aging in human HSC.

Does Preoperative Sinus Rhythm Influence Surgical Ablation's Perioperative Safety in Patients with Atrial Fibrillation?

BACKGROUND: Despite excellent data on lowering long-term stroke and all-cause mortality rates, currently, only 25-40% of atrial fibrillation (AF) patients undergo simultaneous surgical ablation therapy (SA) during cardiac surgery. Surgeon's fear exposing their patients to an additional, unjustified, and disproportionate risk when performing SA in AF patients presenting with sinus rhythm (SR) before surgery. To clarify the influence of preoperative SR before SA for AF, we conducted a subgroup analysis of the German Cardiosurgical Atrial Fibrillation (CASE-AF) register. METHODS: Between September 2016 and August 2020, 964 AF patients with an underlying cardiac disease were scheduled for surgery with SA and enrolled in the CASE-AF register. Data prospectively were collected and analyzed retrospectively. We divided the entire cohort into an SR-group (38.2%, N = 368) and an AF-group (61.8%, N = 596), based on preoperative heart rhythm. RESULTS: Over half of the patients were moderately affected by their AF, with no difference between the groups (European Heart Rhythm Association class ≥IIb: SR-group 54.2% versus AF-group 58.5%, P = .238). The AF-group had a higher preoperative EuroSCORE II (4.8 ± 8.0% versus 4.2 ± 6.3%, P = .014). In-hospital mortality (SR-group 0.8% versus AF-group 1.7%, P = .261), major perioperative adverse cardiac and cerebrovascular events (SR-group 2.7% versus AF-group 3.5%, P = .500), and the new pacemaker implantation rate (SR-group 6.0% versus AF-group 5.9%, P = .939) were low and showed and no group difference. Logistic regression analysis showed a protective effect for preoperative SR to perioperative complications in AF patients undergoing SA (odds ratio (OR) 0.72 (95% CI 0.52 - 0.998); P = .0485). CONCLUSIONS: Concomitant SA in AF patients presenting in SR before cardiac surgery is safe, has a low perioperative risk profile, and should be carried out with almost no exceptions.

Pericardial fluids or Cardiopulmonary Bypass-Is There a Major Culprit for Changes in Coagulation and Inflammation?

BACKGROUND: From the results of a previous study, it remained to be investigated if a perioperative rise of few tested coagulation and inflammation markers is caused by conventional cardiopulmonary bypass (CPB) itself or rather by direct recirculation of pericardial fluids. METHODS: Forty-eight patients operated on with conventional CPB for myocardial revascularization were randomized either for direct recirculation of pericardial suction fluids or for cell saving (CS). RESULTS: Thrombin-antithrombin complexes showed lower values intraoperatively in the CS group (p < 0.0001), and D-dimers tended to remain lower at intensive care unit arrival (p = 0.095). Tests of inflammation markers were less meaningful. CONCLUSION: Direct recirculation of pericardial fluids rather than conventional CPB itself causes major intraoperative changes of some coagulation markers. Pericardial blood loss with direct recirculation should be kept to a minimum to avoid unnecessary activation of coagulation. Inflammation markers need further investigations.

Hemodynamic energy during pulsatile extracorporeal circulation using flexible and rigid arterial tubing: a reassessment.

INTRODUCTION: Pulsatile extracorporeal circulation may improve organ perfusion during cardiac surgery. Some minimally invasive extracorporeal circulation (MiECC) systems allow pulsatile perfusion. The present study investigated the influence of arterial tubing compliance on hemodynamic energy transfer into the patient. METHODS: Aortic models with adult human geometry were perfused in a mock circulation. A MiECC system was connected using either high-compliance silicone tubing or standard kit tubing. Energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) were computed from flow and pressure data. Aortic models with physiological and sub-physiological compliance were tested to assess the influence of the pseudo-patient. RESULTS: Non-pulsatile flow did not generate SHE. SHE during pulsatile flow in the compliant aortic model was significantly higher with kit tubing compared to silicone tubing. Maximum SHE was achieved at 1.6 L/min with kit tubing (7.7% of mean arterial pressure) and with silicone tubing (4.9%). Using the low-compliance aortic model, SHE with kit tubing reached a higher maximum of 14.2% at 1.8 L/min compared to silicone tubing (11.8% at 1.5 L/min). CONCLUSIONS: Flexible arterial tubing did not preserve more hemodynamic energy from a pulsatile pump compared to standard kit tubing in a model of adult extracorporeal circulation. The pseudo-patient's compliance significantly affected the properties of the mock circulation.

[Intrahepatic Hematoma and Pulmonary Embolism in a Young Woman with Oral Contraceptives Complicated by Type II Heparin Induced Thrombocytopenia Requiring ECMO-Therapy: a Case Report]. / Fulminante Lungenarterienembolie bei heparininduzierter Thrombozytopenie Typ II.

A 46-year-old woman on oral contraceptives developed an intrahepatic hematoma due to a benign hepatic tumor. As an incidental finding, a computed tomography showed a pulmonary embolism. Unfractionated heparin was given in a prophylactic dosing in an attempt to balance the risk of further intrahepatic bleeding with that of thrombosis. Ten days later, the patient developed a second pulmonary embolism along with acute right heart failure requiring cardiopulmonary resuscitation. As a sufficient circulation and oxygenation could not be reestablished, a veno-arterial extracorporeal membrane oxygenation (ECMO) was installed. An ELISA-Test, detecting PF4-Heparin associated antibodies, resulted in a positive result for a type II heparin induced thrombocytopenia even in the absence of thrombocytopenia. After hemodynamic and pulmonary stabilization, six days after ECMO-support the cannula was scheduled to be removed. On removal of the venous cannula the patient developed another massive pulmonary embolism with cardiac arrest which led to immediate reinstallation of va-ECMO. Under therapeutic anticoagulation using argatroban the ECMO support continued until the patient was on day 17 successfully weaned.

Influence of 6% Hydroxyethyl Starch 130/0.4 Versus Crystalloid Solution on Structural Renal Damage Markers After Coronary Artery Bypass Grafting: A Post Hoc Subgroup Analysis of a Prospective Trial.

OBJECTIVE: The restriction of hydroxyethyl starch (HES) has mandated changes in volume management based on data of critically ill patients. Reliable data of structural renal damage after HES treatment in cardiac surgical patients are lacking. The influence of 6% HES 130/0.4 was investigated in this study. DESIGN: An exploratory post hoc subgroup analysis of a prospective trial was performed. SETTING: The study was carried out at a university hospital. PARTICIPANTS: Forty-four low-risk cardiac surgical patients were examined. INTERVENTIONS: Twenty-two patients received only crystalloid solutions, and 22 were treated with balanced 6% HES 130/0.4. MEASUREMENTS AND MAIN RESULTS: Functional renal parameters and the structural biomarkers α-glutathione S-transferase, kidney injury molecule-1, liver fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were investigated. Volume balances, vasopressor dosages, blood losses, and coagulation parameters were compared. Most functional and structural renal parameters did not differ between the groups (serum creatinine p = 0.8380). Liver fatty acid-binding protein was transiently higher in the HES group only at 24 hours postoperatively (p = 0.0002). No differences in mortality, acute kidney injury, and need for renal replacement therapy were observed. Blood coagulation was significantly more compromised in the HES group at intensive care unit arrival (factor II, p = 0.0012; factor X, p = 0.0031; thrombocytes, p = 0.0010). Blood losses, and vasopressor dosages tended to be higher in HES-treated patients without significance. CONCLUSION: Overall, the values and time courses of the biomarkers used did not indicate evidence of a mechanism for tubular injury caused by HES.

Extraction of Total RNA from Calcified Human Heart Valves for Gene Expression Analysis.

BACKGROUND: The isolation of high-quality RNA is an important first step in gene expression studies. However, difficult tissue disruption, low cell content and low RNA content makes consistent RNA extraction from human aortic valve tissue a challenging task. METHODS: A protocol has been developed for the successful isolation of high-quality RNA from human aortic valve samples by optimizing RNA extraction protocols based on a comparison of commercial kits. RESULTS: Guanidinium thiocyanate-phenolchloroform extraction was found to be a prerequisite for successful purification. Two protocols based on this extraction were further optimized. RNA quality and quantity were assessed spectrophotometrically, using a Bioanalyzer and by PCR analysis of several housekeeping genes. Optimized parameters included storage in RNAlater™, DNase digestion, the amount of tissue, homogenization time, and freezing of tissue after homogenization. CONCLUSIONS: The modified protocol for fatty and fibrous tissue achieved satisfactory results for gene expression analysis of human aortic valve samples.

On-Pump Nonrobotic Total Endoscopic Coronary Artery Bypass Grafting: An Animal Study.

BACKGROUND: Total endoscopic coronary artery bypass grafting (TECAB) is currently performed exclusively with the help of a telemanipulator. After extensive practice in a biomechanical model, the operation was performed as a nonrobotic approach in an animal study. METHODS: Six large domestic pigs were anesthetized and intubated. Port access and endoscopic vision were used exclusively during the intrathoracic procedure. In five animals, an internal mammary artery was harvested, extracorporeal circulation was established via peripheral vessel access, and the ascending aorta occluded with an intraluminal balloon. In cardioplegic arrest, an anastomosis of internal mammary artery and left anterior descending coronary artery was performed with shortened 7-0 monofil thread running suture. As a terminal study, the animals were humanely killed and the quality of the anastomoses was checked. RESULTS: After a steady learning curve, the fifth animal was operated on successfully and a satisfactory anastomosis was documented. CONCLUSION: Despite demanding differences to humans as shape of thoracic cavity and size of peripheral access vessels, the viability of the nonrobotic TECAB concept was documented in a living animal model.

Renal Function and Urinary Biomarkers in Cardiac Bypass Surgery: A Prospective Randomized Trial Comparing Three Surgical Techniques.

Background Cardiopulmonary bypass procedure is associated with an increased risk of renal impairment. To which extent structural damage causes functional decline is unknown. We evaluated perioperative kidney injury and function in patients treated with conventional extracorporeal circulation (CECC), minimized extracorporeal circulation (MECC), and off-pump coronary artery bypass grafting (OPCAB). Methods Blood and urine samples, collected at baseline and up to 72 hours after surgery from patients of the HEPCON trial (DRKS00007580, 120 patients randomized for heparin management and for surgical technique), were analyzed for differences in renal injury and function. Neutrophil gelatinase-associated lipocalin, α glutathione S-transferase, liver fatty acid-binding protein, and kidney injury molecule-1 were measured as urinary protein markers of renal tubular injury. Serum creatinine, blood urea levels, and estimated glomerular filtration rate were determined to monitor renal function. Results Markers of tubular injury differed significantly between surgical technique groups early after surgery, indicating the most detrimental effect in CECC. Hemolysis and hemodilution correlated with these early changes. A late rise did not show intergroup differences. Time courses of renal function parameters, as well as the development of acute kidney injury in 15 patients (13.5%), were irrespective of surgical technique. Heparin management did not influence renal parameters. Conclusion During coronary artery bypass grafting, CECC temporarily induces more tubular injury than MECC or OPCAB. However, late changes of renal function parameters occur irrespective of extracorporeal perfusion mode and even in off-pump surgery.

Similarity of coagulation and inflammation despite different surgical revascularization strategies - a prospective randomized trial.

BACKGROUND:: Supposedly, minimized extracorporeal circulation or off-pump revascularization as alternatives to conventional extracorporeal circulation (ONCAB) reduce inflammation and coagulation disturbances. METHODS:: One hundred and twenty coronary artery bypass graft (CABG) patients were prospectively randomized for three surgical techniques. Coagulation and inflammation markers were measured up to 72 hours postoperatively. RESULTS:: Coagulation factors I, II, V, X, antithrombin III and C-reactive protein did not differ perioperatively between the groups and increased, as did several other markers, 12 to 72 hours postoperatively. Compared to its alternatives, ONCAB showed the most obvious transient increase in thrombin-antithrombin complexes (p<0.0001), D-dimers (p=0.0059), tissue factor pathway inhibitor (p=0.0005), factor VIII (p=0.0041) and tumor necrosis factor α (p=0.0300) during the operation and up to 12 hours postoperatively. Furthermore, ONCAB generated lower leukocyte and platelet counts and higher values of soluble P-selectin and soluble intercellular adhesion molecule 1 at some time points. CONCLUSIONS:: With similarity in pivot coagulation factors, a specific detrimental influence of ONCAB on common coagulation pathways was excluded. Higher perioperative concentrations of products from the coagulation cascade most likely indicate activation of pericardial blood - recirculated only in ONCAB. Furthermore, with only temporary differences in markers of inflammation, the alternatives to ONCAB altogether were without advantage at 72 hours postoperatively. In the general answer to surgical trauma, the part of modern extracorporeal circulation is possibly overestimated. The study is registered at the German Clinical Trial Registry. Registration number DRKS00007580. URL: https://drks-neu.uniklinik-freiburg.de/drks_web/ URL: http://apps.who.int/trialsearch/.

Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii.

Corynebacterium (C.) kroppenstedtii is a rarely detected agent of bacterial infections in humans. Here, we describe the first case of prosthetic valve endocarditis caused by C. kroppenstedtii. Application of molecular methods using surgically excised valve tissue was a cornerstone for the establishment of the microbiological diagnosis, which is crucial for targeted antimicrobial treatment.

Combination of sildenafil and bosentan for pulmonary hypertension in a human ex vivo model.

PURPOSE: Both sildenafil and bosentan have been used clinically to treat pulmonary arterial hypertension. As these substances target different pathways to modulate vasoconstriction, we investigated the combined effects of both drug classes in isolated human pulmonary vessels. METHODS: Segments of pulmonary arteries (PA) and veins (PV) were harvested from 51 patients undergoing lobectomy. Contractile force was determined isometrically in an organ bath. Vessels were constricted with norepinephrine (NE) to determine effects of sildenafil. They were constricted with ET-1 to assess effects of bosentan, and with NE and ET-1 to evaluate the combination of both substances. RESULTS: Sildenafil (1E-5 M) significantly reduced maximum constriction by NE of both PA (13.0 ± 11.1 vs. 34.9 ± 7.6% relative to KCl induced constriction; n = 6; p < 0.001) and PV (81.2 ± 34.2 vs 121.6 ± 20.8%; n = 6; p < 0.01) but did not affect basal tones. Bosentan (1E-5 M) significantly reduced maximum constriction of PV (56.6 ± 21.5 vs. 172.1 ± 30.0%; n = 6; p < 0.01) by ET-1 and led to a small but insignificant decrease of basal tone (p = 0.07). Bosentan almost completely abolished constriction of PA (1.0 ± 0.9 vs. 74.7 ± 25.7 %; n = 6; p < 0.001) by ET-1, but did not affect basal tone. Bosentan (1E-7 M) significantly attenuated combined ET-1/NE dose-response curves in PA (93.1 ± 47.4 vs. 125.3 ± 41.0%; n = 12; p < 0.001) whereas the effect of sildenafil (1E-5 M) was less pronounced (103.6 ± 20.2%; p < 0.05). Simultaneous administration of both substances showed a significantly greater reduction of maximum constriction in PA compared to individual administration (64.6 ± 26.3 %; p < 0.001). CONCLUSIONS: Sildenafil only at its highest concentration was effective in suppressing NE induced pulmonary vessel contraction. Bosentan was able to completely suppress ET-1 induced contraction of PA and strongly attenuated contraction of PV. The present data suggest a benefit of sildenafil/bosentan combination therapy as they affect different pathways and may allow lower dosages.

Feasibility of aligning creatine kinase MB activity and mass data in multicenter trials using generalized additive modeling.

OBJECTIVES: Elevated serum creatine kinase isoenzyme MB (CK-MB) levels indicate myocardial ischaemia and periprocedural myocardial injury during treatment of heart diseases. We established a method to predict CK-MB mass from activity data based on a prospective pilot study in order to simplify multicentre trials. METHODS: 38 elective cardiac surgery patients without acute myocardial ischaemia and terminal renal failure were recruited. CK-MB mass and activity were determined in venous blood samples drawn preoperatively, postoperatively, 6 h post-op, and 12 h post-op. Linear regression and generalized additive models (GAMs) were applied to describe the relationship of mass and activity. Influences of demographic and perioperative factors on the fit of GAMs was evaluated. The agreement of predicted and measured CK-MB masses was assessed by Bland-Altman analyses. RESULTS: Linear regression provided an acceptable overall fit (r2=0.834) but showed deviances at low CK-MB levels. GAMs did not benefit from the inclusion of age, body mass index, and surgical times. The minimal adequate model predicted CK-MB masses from activities, sex, and sampling time with an r2 of 0.981. Bland-Altman analyses confirmed narrow limits of agreement (spread: 8.87 µg/L) and the absence of fixed (p = 0.41) and proportional (p = 0.21) biases. CONCLUSIONS: GAM-based modelling of CK-MB data in a representative patient cohort allowed to predict CK-MB masses from activities, sex, and sampling time. This approach simplifies the integration of study centers with incompatible CK-MB data into multicentre trials in order to facilitate inclusion of CK-MB levels in statistical models.