CEUS-assessed supraspinatus muscle perfusion improves after tendon repair and predicts anatomical and functional outcome: A 1-year prospective pilot study.

Rotator cuff tear including SSP (Supraspinatus) tendon tears are a very common and often painful condition with several therapeutic options such as tendon repair. Reflected by the high retear rates, the preoperative selection of patients suitable for surgery or conservative treatment, which often yields comparable results, remains difficult. Using contrast-enhanced ultrasound (CEUS), it is possible to quantify the SSP muscle perfusion as a surrogate parameter for its vitality and healing capabilities. In this study, we enrolled 20 patients who underwent an SSP repair for a preoperative and two postoperative (6 months and 1 year) clinical and sonographic exams including CEUS. Along with functional improvement (p < 0.001, Constant score), we found a significant increase in CEUS-assessed muscle perfusion after tendon repair (p < 0.001). Furthermore, weak preoperative muscle perfusion was associated with a higher risk of a retear (χ2 = 0.045) and a moderate trend toward lower postoperative shoulder function that did not reach significance (r = 0.435; p = 0.055, DASH score). If confirmed in larger studies, CEUS might be a valuable additional diagnostic method for a precise selection of patients who most likely profit from a tendon repair and those who can be treated conservatively with an equally good outcome.

An Accelerated Thrombosis Model for Computational Fluid Dynamics Simulations in Rotary Blood Pumps.

PURPOSE: Thrombosis ranks among the major complications in blood-carrying medical devices and a better understanding to influence the design related contribution to thrombosis is desirable. Over the past years many computational models of thrombosis have been developed. However, numerically cheap models able to predict localized thrombus risk in complex geometries are still lacking. The aim of the study was to develop and test a computationally efficient model for thrombus risk prediction in rotary blood pumps. METHODS: We used a two-stage approach to calculate thrombus risk. The first stage involves the computation of velocity and pressure fields by computational fluid dynamic simulations. At the second stage, platelet activation by mechanical and chemical stimuli was determined through species transport with an Eulerian approach. The model was compared with existing clinical data on thrombus deposition within the HeartMate II. Furthermore, an operating point and model parameter sensitivity analysis was performed. RESULTS: Our model shows good correlation (R2 > 0.93) with clinical data and identifies the bearing and outlet stator region of the HeartMate II as the location most prone to thrombus formation. The calculation of thrombus risk requires an additional 10-20 core hours of computation time. CONCLUSION: The concentration of activated platelets can be used as a surrogate and computationally low-cost marker to determine potential risk regions of thrombus deposition in a blood pump. Relative comparisons of thrombus risk are possible even considering the intrinsic uncertainty in model parameters and operating conditions.

Intraventricular Flow Simulations in Singular Right Ventricles Reveal Deteriorated Washout and Low Vortex Formation.

PURPOSE: Patients with a functionally univentricular heart represent one of the most common severe cardiac lesions with a prevalence of 3 per 10,000 live births. Hemodynamics of the singular ventricle is a major research topic in cardiology and there exists a relationship between fluid dynamical features and cardiac behavior in health and disease. The aim of the present work was to compare intraventricular flow in single right ventricle (SRV) patients and subjects with healthy left hearts (LV) through patient-specific CFD simulations. METHODS: Three-dimensional real-time echocardiographic images were obtained for five SRV patients and two healthy subjects and CFD simulations with a moving mesh methodology were performed. Intraventricular vortex formation and vortex formation time (VFT) as well as the turbulent kinetic energy (TKE) and ventricular washout were evaluated. RESULTS: The results show significantly lower values for the VFT and the TKE in SRV patients compared with healthy LV subjects. Furthermore, vortex formation does not progress to the apex in SRV patients. These findings were confirmed by a significantly lower washout in SRV patients. CONCLUSIONS: The study pinpoints the intriguing role of intraventricular flows to characterize performance of SRVs that goes beyond standard clinical metrics such as ejection fraction.

In-vitro performance of a single-chambered total artificial heart in a Fontan circulation.

An in-vitro study was conducted to investigate the general feasibility of using only one pumping chamber of the SynCardia total artificial heart (TAH) as a replacement of the single ventricle palliated by Fontan circulation. A mock circulation loop was used to mimic a Fontan circulation. The combination of both ventricle sizes (50 and 70 cc) and driver (Freedom Driver and Companion C2 Driver) was investigated. Two clinical relevant scenarios (early Fontan; late Fontan) as derived from literature data were set up in the mock loop. The impact of increased transpulmonary pressure gradient, low atrial pressure, and raised central venous pressure on cardiac output was studied. From a hemodynamic point, the single-chambered TAH performed sufficiently in the setting of the Fontan circulation. Increased transpulmonary pressure gradient, from ideal to pulmonary hypertension, decreased the blood flow in combinations by almost 2 L/min. In the early Fontan scenario, a cardiac output of 3-3.5 L/min was achieved using the 50 cc ventricle, driven by the Companion C2 Driver. Even under pulmonary hypertension, cardiac outputs greater than 4 L/min could be obtained with the 70 cc pump chamber in the late Fontan scenario. In the clinically relevant Fontan scenarios, implementation of the single chambered TAH performed successfully from a hemodynamic point of view. The replacement of the failing univentricular heart by a single chamber of the SynCardia TAH may provide an alternative to a complex biventricular repair procedure or ventricular support in Fontan patients.

Optimizing cerebral perfusion and hemodynamics during cardiopulmonary bypass through cannula design combining in silico, in vitro and in vivo input.

Cardiopulmonary bypass (CPB) is a standard technique for cardiac surgery, but comes with the risk of severe neurological complications (e.g. stroke) caused by embolisms and/or reduced cerebral perfusion. We report on an aortic cannula prototype design (optiCAN) with helical outflow and jet-splitting dispersion tip that could reduce the risk of embolic events and restores cerebral perfusion to 97.5% of physiological flow during CPB in vivo, whereas a commercial curved-tip cannula yields 74.6%. In further in vitro comparison, pressure loss and hemolysis parameters of optiCAN remain unaffected. Results are reproducibly confirmed in silico for an exemplary human aortic anatomy via computational fluid dynamics (CFD) simulations. Based on CFD simulations, we firstly show that optiCAN design improves aortic root washout, which reduces the risk of thromboembolism. Secondly, we identify regions of the aortic intima with increased risk of plaque release by correlating areas of enhanced plaque growth and high wall shear stresses (WSS). From this we propose another easy-to-manufacture cannula design (opti2CAN) that decreases areas burdened by high WSS, while preserving physiological cerebral flow and favorable hemodynamics. With this novel cannula design, we propose a cannulation option to reduce neurological complications and the prevalence of stroke in high-risk patients after CPB.

Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump.

BACKGROUND: Treating severe forms of the acute respiratory distress syndrome and cardiac failure, extracorporeal membrane oxygenation (ECMO) has become an established therapeutic option. Neonatal or pediatric patients receiving ECMO, and patients undergoing extracorporeal CO2 removal (ECCO2R) represent low-flow applications of the technology, requiring lower blood flow than conventional ECMO. Centrifugal blood pumps as a core element of modern ECMO therapy present favorable operating characteristics in the high blood flow range (4 L/min-8 L/min). However, during low-flow applications in the range of 0.5 L/min-2 L/min, adverse events such as increased hemolysis, platelet activation and bleeding complications are reported frequently. METHODS: In this study, the hemolysis of the centrifugal pump DP3 is evaluated both in vitro and in silico, comparing the low-flow operation at 1 L/min to the high-flow operation at 4 L/min. RESULTS: Increased hemolysis occurs at low-flow, both in vitro and in silico. The in-vitro experiments present a sixfold higher relative increased hemolysis at low-flow. Compared to high-flow operation, a more than 3.5-fold increase in blood recirculation within the pump head can be observed in the low-flow range in silico. CONCLUSIONS: This study highlights the underappreciated hemolysis in centrifugal pumps within the low-flow range, i.e. during pediatric ECMO or ECCO2R treatment. The in-vitro results of hemolysis and the in-silico computational fluid dynamic simulations of flow paths within the pumps raise awareness about blood damage that occurs when using centrifugal pumps at low-flow operating points. These findings underline the urgent need for a specific pump optimized for low-flow treatment. Due to the inherent problems of available centrifugal pumps in the low-flow range, clinicians should use the current centrifugal pumps with caution, alternatively other pumping principles such as positive displacement pumps may be discussed in the future.

Estimation of left ventricular stroke work based on a large cohort of healthy children.

Left ventricular stroke work is an important prognostic marker to analyze cardiac function. Standard values for children are, however, missing. For clinicians, standards can help to improve the treatment decision of heart failures. For engineers, they can help to optimize medical devices. In this study, we estimated the left ventricular stroke work for children based on modeled pressure-volume loops. A lumped parameter model was fitted to clinical data of 340 healthy children. Reference curves for standard values were created over age, weight, and height. Left ventricular volume was measured with 3D echocardiography, while maximal ventricular pressure was approximated with a regression model from the literature. For validation of this method, we used 18 measurements acquired by a conductance catheter in 11 patients. The method demonstrated a low absolute mean difference of 0.033 J (SD: 0.031 J) for stroke work between measurement and estimation, while the percentage error was 21.66 %. According to the resulting reference curves, left ventricular stroke work of newborns has a median of 0.06 J and increases to 1.15 J at the age of 18 years. Stroke work increases over weight and height in a similar trend. The percentile curves depict the distribution. We demonstrate how reference curves can be used for quantification of differences and comparison in patients.

An energy-dissipation-based power-law formulation for estimating hemolysis.

Hemolysis is a major concern in blood-circulating devices, which arises due to non-physiological stresses on red blood cells from ambient flow environment or moving mechanical structures. Computational fluid dynamics (CFD) and empirical hemolysis prediction models have been increasingly used for the design and optimization of blood-circulating devices. The commonly used power-law models for hemolysis prediction often use Reynolds stress to represent effective stress, tend to over-predict hemolysis and fail to capture trends of flow-related hemolysis. This study proposed a new power-law formulation for the numerical hemolysis prediction. The new formulation related hemolysis to the energy dissipation rate, which could be readily obtained from CFD simulations. The model constants were regressed from existing hemolysis data. The new formulation was tested for three benchmark cases and compared to conventional power-law models. The results showed that the new formulation improved prediction of hemolysis for a broad range of flow regimes. The deviations of the predicted hemolysis from experimental results were within one order, and better correlated with experimental results. This study confirmed that Reynolds stress is the main cause of over-prediction of hemolysis for conventional power-law models. Proportionally, the blood damage predicted with Reynolds stresses is more than one order higher than viscous stress, in terms of energy dissipation.

Contrast-Enhanced Ultrasound (CEUS) as Predictor for Early Retear and Functional Outcome After Supraspinatus Tendon Repair.

Supraspinatus (SSP) tendon tears represent a common indication for shoulder surgery. Yet, prediction of postoperative function and tendon retear remains challenging and primarily relies on morphologic magnetic resonance imaging (MRI)-based parameters, supported by patients' demographic data like age, gender, and comorbidities. Considering continuously high retear rates, especially in patients with larger tears and negative prognostic factors, improved outcome prediction could be of high clinical value. Contrast-enhanced ultrasound (CEUS) enables an assessment of dynamic perfusion of the SSP muscle. As a potential surrogate for muscle vitality, CEUS might reflect functional properties of the SSP and support improved outcome prediction after tendon repair. Fifty patients with isolated SSP tendon tears were prospectively enrolled. Preoperatively, SSP muscle perfusion was quantified by CEUS and conventional morphologic parameters like tear size, fatty infiltration, and tendon retraction were assessed by MRI. At six months follow-up, shoulder function, tendon integrity, and muscle perfusion were reassessed. The predictive value of preoperative CEUS for postoperative shoulder function and tendon integrity was evaluated. 35 patients entered the statistical analysis. Preoperative CEUS-based assessment of SSP perfusion significantly correlated with early postoperative shoulder function (Constant, r = 0.48, p < 0.018) and tendon retear (r = 0.67, p < 0.001). CEUS-based subgroup analysis identified patients with exceptionally high, respectively low risk for tendon retear. CEUS-based assessment of the SSP seemed to predict early shoulder function and tendon retear after SSP repair and allowed to identify patient subgroups with exceptionally high or low risk for tendon retear. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:1150-1158, 2020.

How Computational Modeling can Help to Predict Gas Transfer in Artificial Lungs Early in the Design Process.

Wearable extracorporeal membrane oxygenation (ECMO) circuits may soon become a viable alternative to conventional ECMO treatment. Common device-induced complications, however, such as blood trauma and oxygenator thrombosis, must first be addressed to improve long-term reliability, since ambulatory patients cannot be monitored as closely as intensive care patients. Additionally, an efficient use of the membrane surface can reduce the size of the devices, priming volume, and weight to achieve portability. Both challenges are linked to the hemodynamics in the fiber bundle. While experimental test methods can often only provide global and time-averaged information, computational fluid dynamics (CFD) can give insight into local flow dynamics and gas transfer before building the first laboratory prototype. In this study, we applied our previously introduced micro-scale CFD model to the full fiber bundle of a small oxygenator for gas transfer prediction. Three randomized geometries as well as a staggered and in-line configuration were modeled and simulated with Ansys CFX. Three small laboratory oxygenator prototypes were built by stacking fiber segments unidirectionally with spacers between consecutive segments. The devices were tested in vitro for gas transfer with porcine blood in accordance with ISO 7199. The error of the predicted averaged CFD oxygen saturations of the random 1, 2, and 3 configurations relative to the averaged in-vitro data (over all samples and devices) was 2.4%, 4.6%, 3.1%, and 3.0% for blood flow rates of 100, 200, 300, and 400 ml/min, respectively. While our micro-scale CFD model was successfully applied to a small oxygenator with unidirectional fibers, the application to clinically relevant oxygenators will remain challenging due to the complex flow distribution in the fiber bundle and high computational costs. However, we will outline our future research priorities and discuss how an extended mass transfer correlation model implemented into CFD might enable an a priori prediction of gas transfer in full size oxygenators.

Intra-observer and Device-Dependent Inter-observer Reliability of Contrast-Enhanced Ultrasound for Muscle Perfusion Quantification.

Muscle perfusion quantification by contrast-enhanced ultrasound (CEUS) may facilitate treatment decisions in musculoskeletal disorders. Translation into clinical routine relies on high intra-observer and inter-observer reliability and transferability between ultrasound devices to enable validation and multicenter studies. This study evaluates these aspects for deltoid muscle perfusion quantification, including possible multicenter study setups. One hundred sixty-six CEUS quantifications were conducted on 42 shoulders. Intra-observer reliability revealed a high intra-class correlation coefficient (ICC, r = 0.91) and low coefficient of variation (CV, 10.28%). Inter-observer reliability revealed an ICC of .84 and a CV of 17.1%, but these values decreased when different ultrasound devices were used (ICC = .60, CV = 18.6%). Re-evaluating subgroups with high sectional plane concordance significantly increased reliability (intra-observer: ICC = .97, CV = 5.49%, inter-observer/same device: ICC = .98, CV = 5.83%, varying devices: ICC = .78, CV = 9.8%). CEUS perfusion quantification of the deltoid seems applicable for multicenter studies, yet pooling different ultrasound devices remains critical. Sectional plane concordance appears to be crucial for reliability and transferability of CEUS muscle perfusion quantifications.

The AMANDUS Project-Advanced Microperfusion Assessed Non-Union Diagnostics With Contrast-Enhanced Ultrasound (CEUS) for the Detection of Infected Lower Extremity Non-Unions.

The pre-operative determination of infection plays a decisive role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for the differentiation between aseptic and infected non-unions. Of 109 patients with lower extremity non-unions (tibia n = 78, femur n = 31) osseous perfusion with CEUS was prospectively assessed before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (PE) (arbitrary unit [au]). Significant perfusion differences between aseptic and infected non-unions were evident (PE, p < 0.001). The sensitivity and specificity for the detection of infected tibial and femoral non-unions could be determined with 85.1% and 88.7% (cutoff PE: 81.2 au). CEUS illustrates tibial and femoral non-union perfusion in real time and discriminates reliably between aseptic and infected non-unions. Consequently, when CEUS is integrated into the diagnostic routine algorithm, non-union revision surgery can be planned more accurately as a single or multistep procedure.

On the Accuracy of Hemolysis Models in Couette-Type Blood Shearing Devices.

Hemolysis is one of the most challenging issues faced by blood contacting devices. Empirical hemolysis models often relate hemolysis to shear stress and exposure time. These models were generally derived from the experimental results of Couette-type blood shearing devices, with assumption of uniform exposure time and shear stress. This assumption is not strictly valid since neither exposure time nor shear stress is uniform. Hence, this study evaluated the influence of the nonuniform exposure time and rotor eccentricity or run-out on the accuracy of power-law hemolysis models, using both theoretical and CFD analysis. This work first provided a systematic analysis of the flow regime in a typical Couette shearing device, and showed the axial flow component can be regarded as fully developed laminar plane Poiseuille flow. It was found that the influence of nonuniform exposure time is within 4% for several widely used power-law models, which were validated by steady CFD simulations. A theoretical relationship was then built between the rotor run-out and hemolysis. We noticed that the influence of rotor run-out on hemolysis is within 5% for a moderate rotor run-out ratio of 0.2. Next, transient CFD simulations were performed to investigate the influence of rotor run-out on hemolysis with run-out ratios of 0.1 and 0.2. The results showed negligible effects for a moderate run-out ratio of 0.1. However, a run-out ratio of 0.2 led to a significant increase of hemolysis, resulting from back flows induced by the run-out of the rotor. These findings will be of great importance for the improvement of the hemolysis estimation and blood compatibility design.

Contrast-Enhanced Ultrasound Determines Supraspinatus Muscle Atrophy After Cuff Repair and Correlates to Functional Shoulder Outcome.

BACKGROUND: Muscle degeneration as a consequence of rotator cuff tears is mainly assessed by magnetic resonance imaging. Contrast-enhanced ultrasound (CEUS) is a new functional imaging method to assess microvascular perfusion as a fundamental parameter of muscle tissue vitality. In this cross-sectional study, the authors evaluated supraspinatus muscle perfusion after cuff repair and analyzed its association with functional shoulder outcome and the grade of echogenicity in B-mode ultrasound indicating fatty infiltration. HYPOTHESIS: The authors expected reduced microperfusion of the operated versus the contralateral supraspinatus muscle and a correlation of the muscular microperfusion with functional shoulder outcome. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients who received unilateral repair of the supraspinatus tendon between 2009 and 2014 were invited for a single follow-up examination. Functional scores were assessed, including the Constant-Murley score and American Shoulder and Elbow Surgeons score. CEUS examination was performed bilaterally in an oblique sagittal plane of the supraspinatus fossa. Perfusion was quantified by the parameters wash-in perfusion index (WiPI) and peak enhancement via VueBox quantification software. The results of the Constant-Murley score, American Shoulder and Elbow Surgeons score, and perfusion parameters were referenced to the contralateral shoulder. Echogenicity of the supraspinatus muscle was classified with a 3-point scale as compared with the trapezius muscle. RESULTS: Sixty-seven patients were available, with a mean follow-up of 38.0 ± 18.5 months. Functional assessment showed impaired shoulder function on the operated shoulder as compared with the contralateral side (relative Constant Score [CS], 80% ± 19%). CEUS revealed diminished perfusion on the operated shoulder (WiPI, 55.1% ± 40.2%, P < .001). A strong correlation could be demonstrated between the perfusion deficit and functional impairment (relative WiPI and CS: rs = .644, P < .001). Higher grade of echogenicity in B-mode ultrasound was associated with reduced perfusion. CONCLUSION: CEUS could visualize impaired supraspinatus muscle perfusion after rotator cuff repair as compared with the contralateral, healthy shoulder. With its ability to quantify microvascular perfusion as a surrogate parameter for muscle vitality and function, CEUS may serve as a quantitative method to evaluate rotator cuff muscles.

Increased IgA glycoprotein-2 specific antibody titres in refractory celiac disease.

BACKGROUND & AIMS: In most cases celiac disease (CD) is successfully treated with a gluten-free diet (GFD). However, some patients become refractory to the GFD. Refractory CD (RCD) patients have an increased risk for developing enteropathy associated T-cell lymphoma and early diagnosis is therefore of importance. Currently, RCD diagnosis relies on endoscopy and adequate serological markers are lacking. Antibodies against glycoprotein-2 (GP2A) were described in Crohn's disease (CrD) and active CD but not in ulcerative colitis (UC), suggesting this is a specific marker for small intestinal lesions. METHODS: Sera obtained from patients visiting our outpatient clinic for routine serological tests for diagnosis and/or follow-up of inflammatory bowel disease (n=78), active CD (n=45), GFD (n=34) and RCD (n=15) were analysed for GP2A titres. RESULTS: Increased GP2A-IgA levels in CrD and active CD as compared to controls (p<0.001) and lack thereof in UC was confirmed. However, we could not confirm the association with small bowel localization within the CrD patient group. Within CD patients, we demonstrated a significant decrease of GP2A-IgA titres upon a GFD and increased levels in RCD patients as compared to patients on a GFD. Although GP2A-IgA was not associated with the degree of villous atrophy, GP2A-IgA levels were able to distinguish RCD patients from GFD patients (ROC AUC=0.79, p=0.002). CONCLUSION: Follow-up of GP2A-IgA titres in CD patients on a GFD may help to identify patients at risk for developing RCD.

Differential IL-13 production by small intestinal leukocytes in active coeliac disease versus refractory coeliac disease.

A small fraction of coeliac disease (CD) patients have persistent villous atrophy despite strict adherence to a gluten-free diet. Some of these refractory CD (RCD) patients develop a clonal expansion of lymphocytes with an aberrant phenotype, referred to as RCD type II (RCDII). Pathogenesis of active CD (ACD) has been shown to be related to gluten-specific immunity whereas the disease is no longer gluten driven in RCD. We therefore hypothesized that the immune response is differentially regulated by cytokines in ACD versus RCDII and investigated mucosal cytokine release after polyclonal stimulation of isolated mucosal lymphocytes. Secretion of the T(H)2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients (P = 0.05). In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P = 0.02). IL-13 secretion correlated with other T(H)2 as well as T(H)1 cytokines but not with IL-10 secretion. Overall, the cytokine production pattern of LPL in RCDII showed more similarities with LPL isolated from GFD patients than from ACD patients. Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.

Volume-dependent expression of in-field and out-of-field effects in the proton-irradiated rat lung.

PURPOSE: To investigate whether occurrence of early radiation effects in lung tissue depends on local dose only. METHODS AND MATERIALS: Twenty-five percent, 50%, 66%, 88%, or 100% of the rat lung was irradiated using single fractions of 150-MeV protons. For all volumes, in-field and out-of-field dose-response curves were obtained 8 weeks after irradiation. The pathohistology of parenchymal inflammation, infiltrates, fibrosis, and vascular damage and the relative expression of proinflammatory cytokines interleukin (IL)-1α, transforming growth factor-ß, IL-6, and tumor necrosis factor-α were assessed. RESULTS: For all histologic endpoints, irradiated dose- and volume-dependent in-field and out-of-field effects were observed, albeit with different dynamics. Of note, the out-of-field effects for vascular damage were very similar to the in-field effects. Interestingly, only IL-6 showed a clear dose-dependent increase in expression both in-field and out-of-field, whereas the expression levels of IL-1α, transforming growth factor-ß, and tumor necrosis factor-α were either very low or without a clear dose-volume relation. As such, none of the radiation effects studied depended only on local dose to the tissue. CONCLUSION: The effects of radiation to lung tissue do not only depend on local dose to that tissue. Especially at high-volume irradiation, lung damage seems to present globally rather than locally. The accuracy of predictive modeling may be improved by including nonlocal effects.

Body mass index and creatinine clearance are associated with steady-state serum concentrations of the cell damage marker S100B in renal transplant recipients.

BACKGROUND: S100B is a prominent cell damage marker which can lead to sustained pro-inflammatory signaling. The aim was to investigate cross-sectional associations of steady-state S100B concentrations, particularly with C-reactive protein (CRP), in renal transplant recipients (RTRs) and also to investigate prospectively whether S100B would predict graft failure or mortality. MATERIAL/METHODS: Outpatient RTRs with a graft functioning for >1 year were eligible for participation in this study. S100B was determined at baseline from serum. Mortality and the occurrence of graft failure were recorded until September 2007. Multivariable linear regression analyses were performed to identify potential determinants of S100B. Multivariable Cox regression analyses were performed to investigate S100B as a potential predictor of mortality or graft failure. RESULTS: Five hundred eighty-one RTRs participated in the study. The median S100B concentration was 0.19 (0.14-0.25) microg/l. Recipient age (beta=0.009, p=0.02), body mass index (BMI) (beta=0.021, p<0.001), and creatinine clearance (beta=-015, p<0.001) were independently associated with S100B. During follow-up, 95 RTRs (16.4%) died and 41 (7.1%) developed graft failure. S100B levels did not predict mortality or graft failure. CONCLUSIONS: BMI, creatinine clearance, and age are determinants of steady-state serum S100B concentrations in renal transplant recipients. The association of BMI with S100B suggests that S100B might be a new adipokine.