Publications by authors named "Steven Jacobs"

73 Publications

A Compliant Model of the Ventricular Apex to Study Suction in Ventricular Assist Devices.

ASAIO J 2021 10;67(10):1125-1133

Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.

Ventricular suction is a frequent adverse event in patients with a ventricular assist device (VAD). This study presents a suction module (SM) embedded in a hybrid (hydraulic-computational) cardiovascular simulator suitable for the testing of VADs and related suction events. The SM consists of a compliant latex tube reproducing a simplified ventricular apex. The SM is connected on one side to a hydraulic chamber of the simulator reproducing the left ventricle, and on the other side to a HeartWare HVAD system. The SM is immersed in a hydraulic chamber with a controllable pressure to occlude the compliant tube and activate suction. Two patient profiles were simulated (dilated cardiomyopathy and heart failure with preserved ejection fraction), and the circulating blood volume was reduced stepwise to obtain different preload levels. For each simulated step, the following data were collected: HVAD flow, ventricular pressure and volume, and pressure at the inflow cannula. Data collected for the two profiles and for decreasing preload levels evidenced suction profiles differing in terms of frequency (intermittent vs. every heart beat), amplitude (partial or complete stoppage of the HVAD flow), and shape. Indeed different HVAD flow patterns were observed for the two patient profiles because of the different mechanical properties of the simulated ventricles. Overall, the HVAD flow patterns showed typical indicators of suctions observed in clinics. Results confirmed that the SM can reproduce suction phenomena with VAD under different pathophysiological conditions. As such, the SM can be used in the future to test VADs and control algorithms aimed at preventing suction phenomena.
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http://dx.doi.org/10.1097/MAT.0000000000001370DOI Listing
October 2021

Potential of Medical Management to Mitigate Suction Events in Ventricular Assist Device Patients.

ASAIO J 2021 Sep 9. Epub 2021 Sep 9.

From the Department of Cardiovascular Sciences, Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium Institute of Clinical Physiology, National Research Council, Pisa, Italy Department of Cardiac Surgery, University Hospitals Leuven, Leuven, Belgium.

Ventricular suction is a common adverse event in ventricular assist device (VAD) patients and can be due to multiple underlying causes. The aim of this study is to analyze the potential of different therapeutic interventions to mitigate suction events induced by different pathophysiological conditions. To do so, a suction module was embedded in a cardiovascular hybrid (hydraulic-computational) simulator reproducing the entire cardiovascular system. An HVAD system (Medtronic) was connected between a compliant ventricular apex and a simulated aorta. Starting from a patient profile with severe dilated cardiomyopathy, four different pathophysiological conditions leading to suction were simulated: hypovolemia (blood volume: -900 ml), right ventricular failure (contractility -70%), hypotension (systemic vascular resistance: 8.3 Wood Units), and tachycardia (heart rate:185 bpm). Different therapeutic interventions such as volume infusion, ventricular contractility increase, vasoconstriction, heart rate increase, and pump speed reduction were simulated. Their effects were compared in terms of general hemodynamics and suction mitigation. Each intervention elicited a different effect on the hemodynamics for every pathophysiological condition. Pump speed reduction mitigated suction but did not ameliorate the hemodynamics. Administering volume and inducing a systemic vasoconstriction were the most efficient interventions in both improving the hemodynamics and mitigating suction. When simulating volume infusion, the cardiac powers increased, respectively, by 38%, 25%, 42%, and 43% in the case of hypovolemia, right ventricular failure, hypotension, and tachycardia. Finally, a management algorithm is proposed to identify a therapeutic intervention suited for the underlying physiologic condition causing suction.
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http://dx.doi.org/10.1097/MAT.0000000000001573DOI Listing
September 2021

Surface salt bridges contribute to the extreme thermal stability of an FN3-like domain from a thermophilic bacterium.

Proteins 2021 Aug 18. Epub 2021 Aug 18.

Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.

This study uses differential scanning calorimetry, X-ray crystallography, and molecular dynamics simulations to investigate the structural basis for the high thermal stability (melting temperature 97.5°C) of a FN3-like protein domain from thermophilic bacteria Thermoanaerobacter tengcongensis (FN3tt). FN3tt adopts a typical FN3 fold with a three-stranded beta sheet packing against a four-stranded beta sheet. We identified three solvent exposed arginine residues (R23, R25, and R72), which stabilize the protein through salt bridge interactions with glutamic acid residues on adjacent strands. Alanine mutation of the three arginine residues reduced melting temperature by up to 22°C. Crystal structures of the wild type (WT) and a thermally destabilized (∆Tm -19.7°C) triple mutant (R23L/R25T/R72I) were found to be nearly identical, suggesting that the destabilization is due to interactions of the arginine residues. Molecular dynamics simulations showed that the salt bridge interactions in the WT were stable and provided a dynamical explanation for the cooperativity observed between R23 and R25 based on calorimetry measurements. In addition, folding free energy changes computed using free energy perturbation molecular dynamics simulations showed high correlation with melting temperature changes. This work is another example of surface salt bridges contributing to the enhanced thermal stability of thermophilic proteins. The molecular dynamics simulation methods employed in this study may be broadly useful for in silico surface charge engineering of proteins.
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http://dx.doi.org/10.1002/prot.26218DOI Listing
August 2021

Hemoglobin A1c and preoperative glycemia as a decision tool to help minimise sternal wound complications: a retrospective study in OPCAB patients.

J Cardiothorac Surg 2021 Jul 20;16(1):198. Epub 2021 Jul 20.

Department of Cardiovascular Diseases, Research Unit of Cardiac Surgery, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Background: Poor glycemic control has been associated with an increased risk of wound complications after various types of operations. However, it remains unclear how hemoglobin A1c (HbA1c) and preoperative glycemia can be used in clinical decision-making to prevent sternal wound complications (SWC) following off-pump coronary artery bypass grafting (OPCAB).

Methods: We conducted a retrospective study of 1774 consecutive patients who underwent OPCAB surgery between January 2010 and November 2016. A new four-grade classification for SWC was used. The associations of HbA1c and preoperative glycemia with incidence and grade of SWC were analysed using logistic regression analysis and proportional odds models, respectively.

Results: During a median follow-up of 326 days (interquartile range (IQR) 21-1261 days), SWC occurred in 133/1316 (10%) of non-diabetes and 82/458 (18%) of diabetes patients (p < 0.001). Higher HbA1c was significantly associated with a higher incidence of SWC (odds ratio, OR 1.24 per 1% increase, 95% confidence interval, CI 1.04;1.48, p = 0.016) as well as a higher grade of SWC (OR 1.25, 95% CI 1.06;1.48, p = 0.010). There was no association between glycemia and incidence (p = 0.539) nor grade (p = 0.607) of SWC. Significant modifiers of these effects were found: HbA1c was associated with SWC in diabetes patients younger than 70 years (OR 1.41, 95% CI 1.17;1.71, p < 0.001), whereas it was not in those older than 70 years. Glycemia was associated with SWC in patients who underwent non-urgent surgery (OR 2.48, 95% CI 1.26;4.88, p = 0.009), in diabetes patients who received skeletonised grafts (OR 4.83, 95% CI 1.28;18.17, p = 0.020), and in diabetes patients with a BMI < 30 (OR 2.19, 95% CI 1.01;4.76, p = 0.047), whereas it was not in the counterparts of these groups.

Conclusions: Under certain conditions, HbA1c and glycemia are associated SWC following OPCAB. These findings are helpful in planning the procedure with minimal risk of SWC.
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http://dx.doi.org/10.1186/s13019-021-01580-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290607PMC
July 2021

Exercise physiology in left ventricular assist device patients: insights from hemodynamic simulations.

Ann Cardiothorac Surg 2021 May;10(3):339-352

Department of Cardiovascular Sciences, Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.

Left ventricular assist devices (LVADs) assure longer survival to patients, but exercise capacity is limited compared to normal values. Overall, LVAD patients show high wedge pressure and low cardiac output during maximal exercise, a phenomenon hinting at the need for increased LVAD support. Clinical studies investigating the hemodynamic benefits of an LVAD speed increase during exercise, ended in inhomogeneous and sometimes contradictory results. The native ventricle-LVAD interaction changes between rest and exercise, and this evolution is complex, multifactorial and patient-specific. The aim of this paper is to provide a comprehensive overview on the patient-LVAD interaction during exercise and to delineate possible therapeutic strategies for the future. A computational cardiorespiratory model was used to simulate the hemodynamics of peak bicycle exercise in LVAD patients. The simulator included the main cardiovascular and respiratory impairments commonly observed in LVAD patients, so as to represent an average hemodynamic response to exercise. In addition, other exercise responses were simulated, by tuning the chronotropic, inotropic and vascular functions, and implementing aortic regurgitation and stenosis in the simulator. These profiles were tested under different LVAD speeds and LVAD pressure-flow characteristics. Simulations output showed consistency with clinical data from the literature. The simulator allowed the working condition of the assisted ventricle at exercise to be investigated, clarifying the reasons behind the high wedge pressure and poor cardiac output observed in the clinics. Patients with poorer inotropic, chronotropic and vascular functions, are likely to benefit more from an LVAD speed increase during exercise. Similarly, for these patients, a flatter LVAD pressure-flow characteristic can assure better hemodynamic support under physical exertion. Overall, the study evidenced the need for a patient-specific approach on supporting exercise hemodynamics. In this frame, a complex simulator can constitute a valuable tool to define and test personalized speed control algorithms and strategies.
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http://dx.doi.org/10.21037/acs-2020-cfmcs-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185386PMC
May 2021

Left Impella®-device as bridge from cardiogenic shock with acute, severe mitral regurgitation to MitraClip®-procedure: a new option for critically ill patients.

Eur Heart J Acute Cardiovasc Care 2021 May;10(4):415-421

Department of Adult Intensive Care, Royal Brompton and Harefield NHS Foundation Trust, Sydney St, Chelsea, London SW3 6NP, UK.

Aims: Patients presenting with cardiogenic shock (CS) related to acute, severe mitral regurgitation (MR) are often considered too ill for immediate surgical intervention. Therefore, other less invasive techniques for haemodynamic stabilization should be explored. The purpose of this exploratory study was to investigate the feasibility and outcomes in patients with CS due to severe MR by using a novel approach combining haemodynamic stabilization with left Impella-support plus MR-reduction using MitraClip®.

Methods And Results: We analysed whether a combined left Impella®/MitraClip®-procedure in a rare population of CS-patients with acute MR requiring mechanical ventilation is a feasible strategy to recovery in patients who had been declined cardiac surgery. Six INTERMACS-1 CS-patients with acute MR were studied at two tertiary cardiac intensive care units. The mean EURO-II score was 39 ± 19% and age 66.8 ± 4.9 years. All patients had an initial pulmonary capillary wedge pressure >20 mmHg and pulmonary oedema necessitating invasive ventilation. Cardiac output was severely impaired (left ventricular outflow tract velocity time index 9.8 ± 1.8 cm), requiring mechanical circulatory support (MCS) (Impella®-CP; mean flow 2.9 ± 1.8 L per minute; mean support 9.7 ± 6.0 days). Despite MCS-guided unloading, weaning from ventilation failed due to persisting pulmonary oedema necessitating MR-reduction. In all cases, the severe MR was reduced to mild using percutaneous MitraClip®-procedure, followed by successful weaning from invasive ventilation. Survival to discharge was 86%, with all surviving and rare readmission for heart failure at 6 months.

Conclusions: A combined Impella®/MitraClip®-strategy appears a novel, feasible alternative for weaning CS-patients presenting with acute, severe MR. Upfront Impella®-stabilization facilitates safe bridging to Mitraclip®-procedure and the staged approach facilitates successful weaning from ventilatory support.
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http://dx.doi.org/10.1093/ehjacc/zuaa031DOI Listing
May 2021

A comparative 30-day outcome analysis of inpatient evaluation vs outpatient testing in patients presenting with chest pain in the high-sensitivity troponin era. A propensity score matched case-control retrospective study.

Clin Cardiol 2020 Nov 4;43(11):1248-1254. Epub 2020 Aug 4.

Heart Institute, Geisinger Medical Center, Danville, Pennsylvania, USA.

Background: The best disposition of chest pain patients who rule out for myocardial infarction (MI) but have non-low clinical risk scores in the high-sensitivity troponin era is not well studied.

Hypothesis: In carefully selected patients who rule out for MI, and have a high-sensitivity troponin T ≤ 50 ng/L with an absolute increase less than 5 ng/L on repeat measurements, early emergency room (ER) discharge might be equivalent to inpatient evaluation in regards to 30-day incidence of adverse cardiac events (ACEs) regardless of the clinical risk score.

Methods: A total of 12 847 chest pain patients presenting to our health system ERs from January 2017 to September 2019 were retrospectively investigated. A propensity score matching algorithm was used to account for baseline differences between admitted and discharged cohorts. We then estimated and compared the incidence of 30-day and 1-year composite ACEs (MI, urgent revascularization, or cardiovascular death) between both groups. A multivariate Cox regression model was used to evaluate the effect of admission on outcomes.

Results: A total of 2060 patients were matched in 1:1 fashion. The primary endpoint of 30-day composite ACEs occurred in 0.6% and 0.4% of the admission and the discharged cohorts, respectively (P = .76). One-year composite ACEs was also similar between both groups (4% vs 3.7%, P = .75). In a multivariate Cox regression model, the effect of inpatient evaluation was neutral (hazard ratio 1.1, confidence interval 0.62-1.9, P = .75).

Conclusions: Inpatient evaluation was not associated with better outcomes in our selected group of patients. Larger-scale randomized trials are needed to confirm our findings.
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http://dx.doi.org/10.1002/clc.23435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661656PMC
November 2020

Comparative outcome analysis of stable mildly elevated high sensitivity troponin T in patients presenting with chest pain. A single-center retrospective cohort study.

Int J Cardiol Heart Vasc 2020 Oct 23;30:100586. Epub 2020 Jul 23.

Heart Institute, Geisinger Medical Center, United States.

Background: The ideal high-sensitivity troponin (hsTn) cutoff for identifying those at low risk of 30 days events is debated; however, the 99th percentile overall or gender-specific upper reference limit (URL) is most commonly used. The magnitude of risk and the best management strategy for those with low-level hsTn elevation hasn't been extensively studied.

Methods: We conducted a retrospective cohort analysis including 4396 chest pain patients (542 with low-level hsTn elevation) who ruled out for myocardial infarction (MI), had a stable high-sensitivity troponin T (hsTnT) levels (defined as < 5 ng/l inter-measurements increase in hsTnT levels), and were discharged from the emergency department without further ischemic testing. The aim of the study was to compare the 30-day incidence of adverse cardiac events (ACE) between patients with undetectable high-sensitivity troponin T (hsTnT) (group 1), patients with hsTnT within the 99th percentile sex-specific URL (group 2), and patients with low-level hsTnT elevation (between the 99th percentile URL and ≤ 50 ng/l) (group 3).

Results: 30-day event rates were very low 0.1%, 0.6%, and 0.4% for hsTnT groups 1, 2, and 3 respectively (overall P = 0.041, for groups 2 & 3 interaction P = 0.74). 30-day all-cause mortality, as well as 1-year all-cause and cardiovascular mortalities, occurred more frequently in those with low-level hsTnT elevation as did 1-year composite ACE.

Conclusion: In conclusion, 30-day adverse event rates were very low in those with stable low-level hsTnT elevation who ruled out for MI and were discharged from the emergency department without further inpatient testing.
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http://dx.doi.org/10.1016/j.ijcha.2020.100586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385443PMC
October 2020

Heart team 2.0: A decision tree for minimally invasive and hybrid myocardial revascularization.

Trends Cardiovasc Med 2021 08 24;31(6):382-391. Epub 2020 Jul 24.

Department of Cardiovascular Diseases, Research Unit of Cardiac Surgery, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address:

Recent years have seen an important shift in the target population for myocardial revascularization. Patients are increasingly presenting with more complex coronary artery disease (CAD), but also with multiple comorbidities and frailty. At the same time, minimally invasive strategies such as Minimally Invasive Direct Coronary Artery Bypass Grafting (MIDCAB) and Percutaneous Coronary Interventions (PCI) have been developed, which might be more appealing for this group of patients. As a result, the landscape of options for myocardial revascularization is evolving while adequate use of all resources is required to ensure optimal patient care. Heart Teams are confronted with the challenge of incorporating the new minimally invasive strategies into the decision process, yet current guidelines do not fully address this challenge. In this review, the current evidence regarding outcomes, indications, benefits, and risks of off-pump coronary artery bypass grafting (OPCAB), MIDCAB, PCI, and hybrid coronary revascularization (HCR) are discussed. Based on this evidence and on experiences from Heart Team discussions, a new decision tree is proposed that incorporates recent advances in minimally invasive revascularization strategies, thereby optimizing adequate delivery of care for each individual patient's needs. Introducing all important considerations in a logical way, this tool facilitates the decision-making process and might ensure appropriate use of resources and optimal care for individual patients.
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http://dx.doi.org/10.1016/j.tcm.2020.07.005DOI Listing
August 2021

Limiting factors of peak and submaximal exercise capacity in LVAD patients.

PLoS One 2020 9;15(7):e0235684. Epub 2020 Jul 9.

Department of Cardiovascular Sciences, Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.

Aims: Although patients supported with a Continuous-Flow Left Ventricular Assist Device (CF-LVAD) are hemodynamically stable, their exercise capacity is limited. Hence, the aim of this work was to investigate the underlying factors that lead to peak and submaximal exercise intolerance of CF-LVAD supported patients.

Methods: Seven months after CF-LVAD implantation, eighty three patients performed a maximal cardiopulmonary exercise test and a six minute walk test. Peak oxygen uptake and the distance walked were measured and expressed as a percentage of the predicted value (%VO2p and %6MWD, respectively). Preoperative conditions, echocardiography, laboratory results and pharmacological therapy data were collected and a correlation analysis against %VO2p and %6MWD was performed.

Results: CF-LVAD patients showed a relatively higher submaximal exercise capacity (%6MWD = 64±16%) compared to their peak exertion (%VO2p = 51±14%). The variables that correlated with %VO2p were CF-LVAD parameters, chronotropic response, opening of the aortic valve at rest, tricuspid insufficiency, NT-proBNP and the presence of a cardiac implantable electronic device. On the other hand, the variables that correlated with %6MWD were diabetes, creatinine, urea, ventilation efficiency and CF-LVAD pulsatility index. Additionally, both %6MWD and %VO2p were influenced by the CF-LVAD implantation timing, calculated from the occurrence of the cardiac disease.

Conclusion: Overall, both %6MWD and %VO2p depend on the duration of heart failure prior to CF-LVAD implantation. %6MWD is primarily determined by parameters underlying the patient's general condition, while %VO2p mostly relies on the residual function and chronotropic response of the heart. Moreover, since %VO2p was relatively lower compared to %6MWD, we might infer that CF-LVAD can support submaximal exercise but is not sufficient during peak exertion. Hence concluding that the contribution of the ventricle is crucial in sustaining hemodynamics at peak exercise.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235684PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347393PMC
September 2020

In Pursuit of Stability Enhancement of a Prostate Cancer Targeting Antibody Derived from a Transgenic Animal Platform.

Sci Rep 2020 06 16;10(1):9722. Epub 2020 Jun 16.

Janssen Biotherapeutics, 1400 McKean Road, Spring House, PA, 19477, United States.

Accelerated timelines necessitate the discovery of fully human antibodies as biotherapeutics using transgenic animals with a notion that such mAbs bypass humanization. A transgenic animal derived mAb (PCa75) targeted against a prostate cancer antigen had several 'unusual residues' (rare somatic hypermutations, rSHM, with positional frequency of <1%) that resulted in compromised biophysical properties (Tm = 61 °C and intrinsic stability ΔGu = 24.3 kJ/mol) and a sub-optimal immunogenicity profile. In our quest for quality medicine, we pursued antibody engineering strategies to enhance the stability of PCa75. PCa62, an engineered variant of PCa75, retained function while significantly improving the drug-like attributes of the molecule (Tm = 75 °C and intrinsic stability ΔGu = 63.5 kJ/mol). rSHM is rather prevalent, 18 out the 21 approved transgenic animal-derived antibodies have at least one 'unusual residue'. Thus, engineering of rSHM remains critical to enhance the stability and minimize immunogenicity risk of biotherapeutics.
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http://dx.doi.org/10.1038/s41598-020-66636-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298045PMC
June 2020

Prevalence and Predictors of Obstructive Coronary Artery Disease in Nonlow-risk Acute Chest Pain Patients Who Rule Out for Myocardial Infarction in the High-sensitivity Troponin Era.

Crit Pathw Cardiol 2021 03;20(1):10-15

From the Heart Institute, Geisinger Medical Center, Danville, PA.

Objectives: The best management approach for chest pain patients who rule out for myocardial infarction (MI) in the high-sensitivity troponin (hsTn) era remains elusive. Patients, especially those with nonlow clinical risk scores, are often referred for inpatient ischemic testing to uncover obstructive coronary artery disease (CAD). Whether the prevalence of obstructive CAD in this cohort is high enough to justify routine testing is not known.

Methods: We conducted a retrospective cohort analysis of 1517 emergency department chest pain patients who ruled out for MI by virtue of a stable high-sensitivity troponin T (hsTnT) levels (defined as <5 ng/L intermeasurements increase) and were admitted for inpatient testing.

Results: Abnormal ischemia evaluation (including 5.9% with evidence of fixed wall motion or perfusion defects) was 11.9%. Of those undergoing invasive angiography (n = 292), significant coronary stenoses (≥70% or unstable lesions) and multivessel CAD occurred in 16.8% and 5.5%, respectively. In a multivariate logistic regression model, known CAD, prior MI, chest pain character, mildly elevated hsTnT, and left ventricular ejection fraction <40% were predictive of an abnormal ischemia evaluation result, whereas electrocardiography findings and the modified History, EKG, Age, Risk factors, and troponin (HEART) score were not. Of note, 30-day adverse cardiac events were strikingly low at 0.4% with no deaths despite an overwhelming majority (>90%) of patients scoring intermediate or high on the modified HEART score.

Conclusions: A considerable percentage of acute chest pain patients who rule out for MI by hsTn had evidence of obstructive CAD, and the modified HEART score was not predictive of an abnormal ischemia evaluation.
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http://dx.doi.org/10.1097/HPC.0000000000000229DOI Listing
March 2021

Weight evolution after implantation of left ventricular assist device: Do we need to interfere?

Int J Artif Organs 2020 Oct 22;43(10):671-676. Epub 2020 Feb 22.

Department of Cardiac Surgery, Universitaire Ziekenhuizen Leuven, Leuven, Belgium.

Objectives: Weight change after left ventricular assist device implantation may influence outcomes and can affect transplant candidacy. We questioned if there is a systematic weight change after left ventricular assist device implantation and examined the evolution in functional capacity.

Methods: A retrospective analysis of 84 patients who received a left ventricular assist device in Universitaire Ziekenhuizen Leuven between 2008 and 2016 was performed. Patients were divided into four groups based on their baseline body mass index, and we also examined weight evolution for patients presenting with new-onset heart failure versus those suffering from chronic heart failure. Body mass index was assessed at baseline, 6, 12, 18, and 24 months. To indicate the functional capacity, we analyzed the results of routine 6-Minute Walk Test performed at 6, 12, and 18 months.

Results: During the first 6 months after surgery, the underweight patients evolved to normal weight and the body mass index of the obese patients reduced significantly. Afterward, all patients gained weight. The weight loss of the obese was not maintained over time. The weight of patients with normal weight and overweight evolved to overweight and obesity, respectively. No body mass index changes were demonstrated for patients presenting with new-onset heart failure, and the body mass index of patients suffering from chronic HF significantly increased. There was a significant improvement in functional capacity at 6 months, but this level remained unchanged at 12 and 18 months after surgery.

Conclusion: Although the initial 6 months evolve beneficial, all patients gain weight in the second year and do not further improve their exercise capacity.
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http://dx.doi.org/10.1177/0391398820906554DOI Listing
October 2020

Skeletonisation contributing to a reduction of sternal wound complications: a retrospective study in OPCAB patients.

J Cardiothorac Surg 2019 Sep 9;14(1):162. Epub 2019 Sep 9.

Department of Cardiovascular Diseases, Research Unit of Cardiac Surgery, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.

Background: Sternal wound complications (SWC) are a rare but potentially life-threatening complication after coronary artery bypass grafting (CABG) surgery. Especially the use of bilateral IMA (BIMA) grafts as opposed to single IMA (SIMA) grafts is associated with an increased risk of SWC. Skeletonised harvesting has been proposed to reduce this risk. The purpose of this study was to retrospectively investigate the effect of skeletonisation on SWC after off-pump coronary artery bypass grafting (OPCAB) in a centre with a high volume of off-pump procedures and high frequencies of BIMA.

Methods: From January 2010 to November 2016, 1900 consecutive patients underwent OPCAB surgery at the University Hospitals of Leuven. The first group (n = 1487) received non-skeletonised IMA grafts, whereas the second group (n = 413) received skeletonised grafts. Optimal wound management was pursued in all patients. A new four-grade classification for SWC was developed. Incidence and grade of SWC as well as overall survival were assessed.

Results: Analysis of diabetic patients showed a lower incidence of SWC in the skeletonised (12/141, 8.5%) compared to the non-skeletonised group (82/414, 19.8%) [odds ratio 0.46, 95% confidence interval (0.23;0.88), p = 0.019] as well as a lower grade [0.45 (0.24;0.871), p = 0.018]. There was no significant effect on overall survival [0.67 (0.19;2.32), p = 0.529]. Subanalysis of this population revealed that the observed effects were most prominent in patients receiving BIMA grafts, with 6/56 (10.7%) SWC in the skeletonised and 62/252 (24.6%) in the non-skeletonised group [0.37 (0.15;0.90), p = 0.028 for incidence], as well as a lower grade [0.36 (0.15;0.88), p = 0.025]. These advantages were not significant in diabetic patients receiving SIMA grafts nor in the full study population.

Conclusions: This study, using a more sensitive classification of SWC, shows in a large group of patients that, in combination with optimized wound management, the skeletonisation technique is associated with a clear reduction in the incidence and grade of SWC in diabetic patients receiving BIMA grafts. This encourages the extension of BIMA use in OPCAB to this risk population.
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http://dx.doi.org/10.1186/s13019-019-0985-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734214PMC
September 2019

General Anesthesia Versus Monitored Anesthesia Care for Transfemoral Transcatheter Aortic Valve Implantation: A Retrospective Study in a Single Belgian Referral Center.

J Cardiothorac Vasc Anesth 2019 Dec 23;33(12):3283-3291. Epub 2019 Jun 23.

Department of Anaesthesiology, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

Objective: The objective of this study was to compare the effect of general anesthesia (GA) versus monitored anesthesia care (MAC) on post-interventional outcomes in patients undergoing transfemoral transcatheter aortic valve implantation (TAVI).

Design: Retrospective before-after study using a quasi-experimental design.

Setting: University Hospitals Leuven, a single Belgian referral center.

Participants: Patients undergoing transfemoral TAVI from March 1, 2014, to December 31, 2017, were included.

Interventions: GA was switched to MAC at the authors' institution for transfemoral TAVI in April 2016, and outcomes of patients who received GA were compared with those who received MAC.

Measurements And Main Results: The primary outcomes were length of stay in the intensive care unit and hospital. Secondary outcomes included standardized endpoints for TAVI trials as suggested by the Valve Academic Research Consortium, the incidence of vasopressor use, maximum dose of vasopressors, procedural time, and total anesthesia time. In the period studied, 178 patients underwent transfemoral TAVI (GA: n = 85; MAC: n = 93). Implementation of MAC was associated with a significant reduction in total length of hospital stay (7.6 [6.05-9.15] v 5.48 [4.58-6.38] d; p = 0.02); vasopressor requirements; and procedural and total anesthesia time. Length of intensive care unit stay and Valve Academic Research Consortium endpoints were not significantly different.

Conclusions: In the authors' institution, implementation of MAC for patients undergoing transfemoral TAVI resulted in a significant reduction of hospital length of stay and increased operating room efficiency. Results could be confounded by increasing operator experience and improved implantation techniques.
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http://dx.doi.org/10.1053/j.jvca.2019.06.027DOI Listing
December 2019

A 117-year retrospective analysis of Pennsylvania tick community dynamics.

Parasit Vectors 2019 Apr 29;12(1):189. Epub 2019 Apr 29.

Department of Entomology, Pennsylvania State University, W-104 Millennium Science Complex, University Park, PA, 16802, USA.

Background: Tick-borne diseases have been increasing at the local, national, and global levels. Researchers studying ticks and tick-borne diseases need a thorough knowledge of the pathogens, vectors, and epidemiology of disease spread. Both active and passive surveillance approaches are typically used to estimate tick population size and risk of tick encounter. Our data consists of a composite of active and long-term passive surveillance, which has provided insight into spatial variability and temporal dynamics of ectoparasite communities and identified rarer tick species. We present a retrospective analysis on compiled data of ticks from Pennsylvania over the last 117 years.

Methods: We compiled data from ticks collected during tick surveillance research, and from citizen-based submissions. The majority of the specimens were submitted by citizens. However, a subset of the data was collected through active methods (flagging or dragging, or removal of ticks from wildlife). We analyzed all data from 1900-2017 for tick community composition, host associations, and spatio-temporal dynamics.

Results: In total there were 4491 submission lots consisting of 7132 tick specimens. Twenty-four different species were identified, with the large proportion of submissions represented by five tick species. We observed a shift in tick community composition in which the dominant species of tick (Ixodes cookei) was overtaken in abundance by Dermacentor variabilis in the early 1990s and then replaced in abundance by I. scapularis. We analyzed host data and identified overlaps in host range amongst tick species.

Conclusions: We highlight the importance of long-term passive tick surveillance in investigating the ecology of both common and rare tick species. Information on the geographical distribution, host-association, and seasonality of the tick community can help researchers and health-officials to identify high-risk areas.
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http://dx.doi.org/10.1186/s13071-019-3451-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489237PMC
April 2019

Clinical outcomes of heart-team-guided treatment decisions in high-risk patients with aortic valve stenosis in a health-economic context with limited resources for transcatheter valve therapies.

Acta Cardiol 2019 Dec 3;74(6):489-498. Epub 2018 Dec 3.

Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium.

Transcatheter aortic valve implantation (TAVI) is the preferred treatment modality for patients with severe aortic stenosis at high or prohibitive risk for surgical aortic valve replacement (SAVR). We aimed to evaluate real-world outcomes after treatment according to the decisions of the multidisciplinary heart team in a Belgian health-economic context. Four hundred and five high-risk patients referred to a tertiary centre between 1 March 2008 and 31 December 2015 were screened and planned to undergo SAVR, TAVI or medical treatment (MT). Patients undergoing SAVR had lower Society of Thoracic Surgeons scores and Euroscore-II when compared to TAVI or MT (median [IQR]: 6[4-8]; 7[5-10]; 8[6-13];  < .001 and 6[4-10]; 8[5-15]; 8[4-16];  = .006). At 1 year all-cause mortality was 14, 17 and 51% with SAVR, TAVI and MT, respectively ( < .001). Cardiovascular death and disabling stroke occurred in 9, 7 and 35% ( < .001) and 2, 2.7 and 1.7% ( = .91). According to Valve-Academic-Research-Consortium-II criteria, device success was 95 and 92% for TAVI and SAVR. The combined safety endpoint at 30 days favoured TAVI (22% vs. 47%) ( < .001). The combined efficacy endpoint at 1 year was comparable between groups (38 and 40%;  = .703). Finally, hospital stay was shorter with TAVI vs. SAVR (9[6-14] and 16[12-22] days;  < .001). Limited resources for transcatheter valve therapies in Belgium push a significant number of patients to SAVR, while TAVI in even higher risk patients translates into similar outcomes and shorter hospital stay. These findings underscore the need for broadening indications for TAVI, as well as readjustment of the budgetary allocations for hospitals in Belgium.
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http://dx.doi.org/10.1080/00015385.2018.1522461DOI Listing
December 2019

Waarnemingen.be - Plant occurrences in Flanders and the Brussels Capital Region, Belgium.

PhytoKeys 2017 8(85):1-10. Epub 2017 Aug 8.

Natuurpunt Studie, Coxiestraat 11, 2800 Mechelen, Belgium.

Waarnemingen.be - Plant occurrences in Flanders and the Brussels Capital Region, Belgium is a species occurrence dataset published by Natuurpunt. The dataset contains almost 1.2 million plant occurrences of 1,222 native vascular plant species, mostly recorded by volunteers (citizen scientists), mainly since 2008. The occurrences are derived from the database http://www.waarnemingen.be, hosted by Stichting Natuurinformatie and managed by the nature conservation NGO Natuurpunt. Together with the datasets Florabank1 (Van Landuyt and Brosens 2017) and the Belgian IFBL (Instituut voor Floristiek van België en Luxemburg) Flora Checklists (Van Landuyt and Noé 2015), the dataset represents the most complete overview of indigenous plants in Flanders and the Brussels Capital Region.
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http://dx.doi.org/10.3897/phytokeys.85.14925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624210PMC
August 2017

A Scoping Review Examining Nursing Student Peer Mentorship.

Authors:
Steven Jacobs

J Prof Nurs 2017 May - Jun;33(3):212-223. Epub 2016 Sep 23.

Professor, Clinical Education, George Brown College, Toronto, Ontario, Canada, M5T 2T9. Electronic address:

This paper outlines a scoping review and thematic analysis which was conducted on the topic of nursing student peer mentorship programs. This paper outlines the reasons for conducting a scoping review, includes a description of the scoping review model used for this review, documents the actual scoping review process undertaken, and details the results of the scoping review and thematic analysis on the topic of nursing student peer mentorship. The results of this scoping review and thematic analysis review revealed the following themes related to nursing student peer mentorship: support, dialog, connections, meanings, and a process of socialized learning. Finally, this paper outlines limitations of this scoping review and thematic analysis and offers suggestions for future research.
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http://dx.doi.org/10.1016/j.profnurs.2016.09.004DOI Listing
August 2017

Conformational flexibility of an anti-IL-13 DARPin†.

Protein Eng Des Sel 2017 Jan 23;30(1):31-37. Epub 2016 Nov 23.

Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA 19477, USA

Designed ankyrin repeat proteins (DARPin) are artificial non-immunoglobulin binding proteins with potential applications as therapeutic molecules. DARPin 6G9 binds interleukin-13 with high affinity and blocks the signaling pathway and as such is promising for the treatment of asthma and other atopic diseases. The crystal structures of DARPin 6G9 in the unbound form and in complex with IL-13 were determined at high resolution. The DARPin competes for the same epitope as the IL-13 receptor chain 13Rα1 but does not interfere with the binding of the other receptor chain, IL-4Rα. Analysis of multiple copies of the DARPin molecule in the crystal indicates the conformational instability in the N-terminal cap that was predicted from molecular dynamics simulations. Comparison of the DARPin structures in the free state and in complex with IL-13 reveals a concerted movement of the ankyrin repeats upon binding resulted in the opening of the binding site. The induced-fit mode of binding employed by DARPin 6G9 is very unusual for DARPins since they were designed as particularly stable and rigid molecules. This finding shows that DARPins can operate by various binding mechanisms and suggests that some flexibility in the scaffold may be an advantage.
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http://dx.doi.org/10.1093/protein/gzw059DOI Listing
January 2017

Engineering a targeted delivery platform using Centyrins.

Protein Eng Des Sel 2016 Dec 13;29(12):563-572. Epub 2016 Oct 13.

Janssen Research and Development, L.L.C., 1400 McKean Road, Spring House, PA 19477, USA

Targeted delivery of therapeutic payloads to specific tissues and cell types is an important component of modern pharmaceutical development. Antibodies or other scaffold proteins can provide the cellular address for delivering a covalently linked therapeutic via specific binding to cell-surface receptors. Optimization of the conjugation site on the targeting protein, linker chemistry and intracellular trafficking pathways can all influence the efficiency of delivery and potency of the drug candidate. In this study, we describe a comprehensive engineering experiment for an EGFR binding Centyrin, a highly stable fibronectin type III (FN3) domain, wherein all possible single-cysteine replacements were evaluated for expression, purification, conjugation efficiency, retention of target binding, biophysical properties and delivery of a cytotoxic small molecule payload. Overall, 26 of the 94 positions were identified as ideal for cysteine modification, conjugation and drug delivery. Conjugation-tolerant positions were mapped onto a crystal structure of the Centyrin, providing a structural context for interpretation of the mutagenesis experiment and providing a foundation for a Centyrin-targeted delivery platform.
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http://dx.doi.org/10.1093/protein/gzw054DOI Listing
December 2016

Constellation recovery and impairment evaluation through minimization of the blind EVM.

Opt Express 2016 Sep;24(19):21708-21

We present a new method, blind EVM minimization, for constellation recovery and transmitter impairment evaluation of dual polarization optical signals with complex modulation formats. Using simulated data, for which transmitter impairments are known exactly, the method is shown to be accurate and robust. In addition, the method is successfully tested on measured QPSK and QAM16 data. Because of its relatively long run-time, the method might best be used for defining and measuring transmitter impairments and for judging the performance of faster constellation recovery methods that rely on serial parameter evaluation rather than optimization.
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http://dx.doi.org/10.1364/OE.24.021708DOI Listing
September 2016

Exercise capacity in left ventricular assist device patients with full and partial support.

Eur J Prev Cardiol 2017 01 10;24(2):168-177. Epub 2016 Jul 10.

1 Department of Clinical Cardiac Surgery, Katholieke Universiteit Leuven, Belgium.

Background In the present work, we investigated the exercise capacities of patients with partial flow left ventricular assist devices and its evolution over time. We then compared the exercise capacities of these patients with those of full support ventricular assist device patients. Methods We retrospectively analysed the data of maximal cardiopulmonary exercise tests of ten partial support patients (CircuLite Synergy® Micropump) collected before (PS0), at 3 (PS3) and 6 months (PS6) after implantation. The data were then compared with those of 17 patients (FS6) treated with a full support device (HeartMate II, Thoratec©). For this analysis, we considered the exercise tests performed at 6 months after pump implantation for both groups. Results Peak oxygen uptake evolved in the PS0, PS3 and PS6 groups from 11.5 ± 2.3 to 12.6 ± 2.8 and 12.0 ± 2.7 mL/kg/min, respectively. Heart rate peak increased from PS0 to PS6 (100 ± 17 bpm and 107 ± 22 bpm, p = 0.05). The comparative analysis between PS6 and FS6 groups showed no difference in terms of exercise performance (12.0 ± 2.7 and 13.5 ± 3.0 mL/kg/min, respectively), fatigue perception, ventilation efficiency slope, anaerobic threshold and oxygen uptake efficiency slope. The chronotropic response was also similar in both PS6 and FS6 groups. However, PS6 patients were more often treated with β-blockers and therefore had lower heart rates at rest and at peak exercise than FS6 patients. Conclusions Exercise performance does not change after partial support implantation and stays stable over time. Partial and full support patients show similar exercise performances that attain 41% and 46% of the expected values, respectively.
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http://dx.doi.org/10.1177/2047487316656088DOI Listing
January 2017

Breaking BAD: A Data Serving Vision for Big Active Data.

Proc Int Workshop Distrib Event Based Syst 2016 Jun;2016:181-186

Univ. of California, Riverside.

Virtually all of today's Big Data systems are in nature. Here we describe a project to shift Big Data platforms from passive to . We detail a vision for a scalable system that can continuously and reliably capture Big Data to enable timely and automatic delivery of new information to a large pool of interested users as well as supporting analyses of historical information. We are currently building a Big Active Data (BAD) system by extending an existing scalable open-source BDMS (AsterixDB) in this active direction. This first paper zooms in on the Data Serving piece of the BAD puzzle, including its key concepts and user model.
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http://dx.doi.org/10.1145/2933267.2933313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637738PMC
June 2016

Exercise capacity in ventricular assist device patients: clinical relevance of pump speed and power.

Eur J Cardiothorac Surg 2016 Oct 12;50(4):752-757. Epub 2016 May 12.

Department of Clinical Cardiac Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.

Objectives: Patients with ventricular assist device (VAD) show a limited exercise capacity. The aim of this work is to investigate whether VAD speed increase has an effect on exercise performance in the upright position.

Methods: Fourteen patients implanted with a HeartMate II underwent two cardiopulmonary maximal exercise tests on an upright bicycle ergometer the same day. During one test, VAD speed was set as constant (CONST) and during the other test, VAD speed was increased by 200 rpm each minute (INCR).

Results: No statistical differences were found between the two tests in terms of maximum heart rate, peak oxygen uptake, peak minute ventilation, ventilation efficiency slope and arterial blood pressure. Patients' fatigue perception, measured with a Borg scale, was similar between the two tests over the entire group (15 ± 1 for both CONST and INCR). VAD flow increased from 4.5 ± 0.7 to 6.0 ± 1.0 l/min during CONST and to 7.6 ± 1.4 l/min during INCR. Four patients experienced an easier cycling during INCR, and the other patients noticed no difference. One patient had a suction event during INCR and another had non-sustained ventricular tachycardia at peak exercise. A negative correlation was found between the rate of increase in VAD power during exercise and peak oxygen uptake.

Conclusions: Although VAD speed increase provided an additional pump flow of 1.6 l/min at peak exercise, no significant objective and subjective benefits on patients' exercise performance were observed. Finally, VAD power could be a useful parameter to monitor patients during exercise.
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http://dx.doi.org/10.1093/ejcts/ezw147DOI Listing
October 2016

Reflective learning, reflective practice.

Authors:
Steven Jacobs

Nursing 2016 May;46(5):62-4

Steven Jacobs is faculty of Clinical Education at George Brown College in Ontario, Canada.

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http://dx.doi.org/10.1097/01.NURSE.0000482278.79660.f2DOI Listing
May 2016

Prediction of time dependent survival in HF patients after VAD implantation using pre- and post-operative data.

Comput Biol Med 2016 Mar 12;70:99-105. Epub 2016 Jan 12.

Unit of Medical Technology and Intelligent Information Systems, Dept of Materials Science and Engineering, University of Ioannina, GR 45110 Ioannina, Greece. Electronic address:

Heart failure is one of the most common diseases worldwide. In recent years, Ventricular Assist Devices (VADs) have become a valuable option for patients with advanced HF. Although it has been shown that VADs improve patient survival rates, several complications persist during left VAD (LVAD) support. The stratification scores currently employed are mostly generic, i.e. not specifically built for LVAD patients, and are based on pre-implantation patient data. In this work we apply data mining approaches for the prediction of time dependent survival in patients after LVAD implantation. Moreover, the predictions acquired with the use of pre-implantation data are enriched by employing post-implantation data, i.e. follow-up data. Different clinical scenarios have been depicted and the subsequent conditions are tested in order to identify the optimal set of pre- and post-implant features, as well as the most suitable algorithms for feature selection and prediction. The proposed approach is applied to a real dataset of 71 patients, reporting an accuracy of 84.5%, sensitivity of 87% and specificity of 82%. Based on the reported results, expert cardio-surgeons can be supported in planning the treatment of VAD patients.
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http://dx.doi.org/10.1016/j.compbiomed.2016.01.005DOI Listing
March 2016

A peer mentorship program boosts student retention.

Nursing 2015 Sep;45(9):19-22

Steven Jacobs is professor of clinical education at George Brown College in Toronto, Ontario. At Centennial College in Scarborough, Ontario, Lynda Atack is a professor of nursing, Susan Ng is a coordinator of the nursing program, Roya Haghiri-Vijeh is a professor of nursing, and Christine Dell'Elce is assistant to the dean of community and health studies.

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http://dx.doi.org/10.1097/01.NURSE.0000470424.40180.a0DOI Listing
September 2015

Fusion to a highly stable consensus albumin binding domain allows for tunable pharmacokinetics.

Protein Eng Des Sel 2015 Oct 13;28(10):385-93. Epub 2015 Aug 13.

Janssen Research & Development, L.L.C., 1400 Welsh & McKean Rd., Spring House, Pennsylvania, PA 19454, USA.

A number of classes of proteins have been engineered for high stability using consensus sequence design methods. Here we describe the engineering of a novel albumin binding domain (ABD) three-helix bundle protein. The resulting engineered ABD molecule, called ABDCon, is expressed at high levels in the soluble fraction of Escherichia coli and is highly stable, with a melting temperature of 81.5°C. ABDCon binds human, monkey and mouse serum albumins with affinity as high as 61 pM. The solution structure of ABDCon is consistent with the three-helix bundle design and epitope mapping studies enabled a precise definition of the albumin binding interface. Fusion of a 10 kDa scaffold protein to ABDCon results in a long terminal half-life of 60 h in mice and 182 h in cynomolgus monkeys. To explore the link between albumin affinity and in vivo exposure, mutations were designed at the albumin binding interface of ABDCon yielding variants that span an 11 000-fold range in affinity. The PK properties of five such variants were determined in mice in order to demonstrate the tunable nature of serum half-life, exposure and clearance with variations in albumin binding affinity.
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http://dx.doi.org/10.1093/protein/gzv040DOI Listing
October 2015
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