Kidney transplantation is the preferred treatment for ESRD, and donor kidney shortage urges proper donor-recipient matching. Zero-hour biopsies provide predictive values for short- and long-term ...transplantation outcomes, but are invasive and may not reflect the entire organ. Alternative, more representative methods to predict transplantation outcome are required. We hypothesized that proteins accumulating in preservation fluid during cold ischemic storage can serve as biomarkers to predict post-transplantation graft function.
Levels of 158 proteins were measured in preservation fluids from kidneys donated after circulatory death (Maastricht category III) collected in two Dutch centers (University Medical Center Utrecht and Erasmus Medical Center Rotterdam) between 2013 and 2015. Five candidate biomarkers identified in a discovery set of eight kidneys with immediate function (IF) versus eight with delayed graft function (DGF) were subsequently analyzed in a verification set of 40 additional preservation fluids to establish a prediction model.
Variables tested for their contribution to a prediction model included five proteins (leptin, periostin, GM-CSF, plasminogen activator inhibitor-1, and osteopontin) and two clinical parameters (recipient body mass index BMI and dialysis duration) that distinguished between IF and DGF in the discovery set. Stepwise multivariable logistic regression provided a prediction model on the basis of leptin and GM-CSF. Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.87, and addition of recipient BMI generated a model with an AUC of 0.89, outperforming the Kidney Donor Risk Index and the DGF risk calculator, showing AUCs of 0.55 and 0.59, respectively.
We demonstrate that donor kidney preservation fluid harbors biomarkers that, together with information on recipient BMI, predict short-term post-transplantation kidney function. Our approach is safe, easy, and performs better than current prediction algorithms, which are only on the basis of clinical parameters.
Hexameric hemoprotein (HTHP) is employed as a scaffold protein for the supramolecular assembly and activation of the apoptotic signalling enzyme caspase‐9, using short DNA elements as modular ...recruitment domains. Caspase‐9 assembly and activation on the HTHP platform due to enhanced proximity is followed by combinatorial inhibition at high scaffold concentrations. The DNA recruitment domains allow for reversible switching of the caspase‐9 assembly and activity state using short modulatory DNA strands. Tuning of the recruitment domain affinity allows for generating kinetically trapped active enzyme complexes, as well as for dynamic repositioning of caspases over scaffold populations and inhibition using monovalent sink platforms. The conceptual combination of a highly structured multivalent protein platform with modular DNA recruitment domains provides emergent biomimicry properties with advanced levels of control over protein assembly.
A hexameric protein recruitment platform allows controlled assembly and activation of caspase‐9 enzymes using short DNA sequences as modular recruitment domains. Simple molecular tuning of the DNA recruitment domains enables reversible switching or kinetic inhibition of the proximity‐induced enzyme activation.
A photocrosslinkable protein G variant was used as an adapter protein to covalently and site-specifically conjugate an antibody and an Fc-fusion protein to an oligonucleotide. This modular approach ...enables straightforward decoration of DNA nanostructures with complex native proteins while retaining their innate binding affinity, allowing precise control over the nanoscale spatial organization of such proteins for in vitro and in vivo biomedical applications.
Video-assisted thoracic surgery is traditionally carried out with general anaesthesia and endotracheal intubation with double lumen tube. However, in the last few years procedures, such as ...lobectomies, are being performed with loco-regional anaesthesia, with and without sedation, maintaining the patient awake and with spontaneous breathing, in order to avoid the inherent risks of general anaesthesia, double lumen tube intubation and mechanical ventilation. This surgical approach has also shown to be effective in that it allows a good level of analgesia, maintaining a correct oxygenation and providing a better post-operative recovery. Two case reports are presented in which video-assisted thoracic surgery was used, a lung biopsy and a lung resection, both with epidural anaesthesia and maintaining the patient awake and with spontaneous ventilation, as part of a preliminary evaluation of the anaesthetic technique in this type of surgery.
. Integer‐valued autoregressive (INAR) processes have been introduced to model non‐negative integer‐valued phenomena that evolve in time. The distribution of an INAR(p) process is determined by two ...parameters: a vector of survival probabilities and a probability distribution on the non‐negative integers, called an immigration distribution. This paper provides an efficient estimator of the parameters, and in particular, shows that the INAR(p) model has the Local Asymptotic Normality property.
Aortic valve stenosis (AS) induces compensatory alterations in left ventricular hemodynamics, leading to physiological and pathological alterations in coronary hemodynamics. Relief of AS by ...transcatheter aortic valve implantation (TAVI) decreases ventricular afterload and is expected to improve microvascular function immediately. We evaluated the effect of AS on coronary hemodynamics and the immediate effect of TAVI.
Intracoronary pressure and flow velocity were simultaneously assessed at rest and at maximal hyperemia in an unobstructed coronary artery in 27 patients with AS before and immediately after TAVI and in 28 patients without AS. Baseline flow velocity was higher and baseline microvascular resistance was lower in patients with AS as compared with controls, which remained unaltered post-TAVI. In patients with AS, hyperemic flow velocity was significantly lower as compared with controls (44.5±14.5 versus 54.3±18.6 cm/s; P=0.04). Hyperemic microvascular resistance (expressed in mm Hg·cm·s(-1)) was 2.10±0.69 in patients with AS as compared with 1.80±0.60 in controls (P=0.096). Coronary flow velocity reserve in patients with AS was lower, 1.9±0.5 versus 2.7±0.7 in controls (P<0.001). Improvement in coronary hemodynamics after TAVI was most pronounced in patients without post-TAVI aortic regurgitation. In these patients (n=20), hyperemic flow velocity increased significantly from 46.24±15.47 pre-TAVI to 56.56±17.44 cm/s post-TAVI (P=0.003). Hyperemic microvascular resistance decreased from 2.03±0.71 to 1.66±0.45 (P=0.050). Coronary flow velocity reserve increased significantly from 1.9±0.4 to 2.2±0.6 (P=0.009).
The vasodilatory reserve capacity of the coronary circulation is reduced in AS. TAVI induces an immediate decrease in hyperemic microvascular resistance and a concomitant increase in hyperemic flow velocity, resulting in immediate improvement in coronary vasodilatory reserve.
Highlights ► We study the influence of 27 candidate genes on statin effectiveness. ► We use myocardial infarction as the primary treatment outcome. ► The interaction with statins is most significant ...for SCARB1 rs4765615. ► None of the ten associated SNPs reach statistical significance in the replication study. ► PCSK9 670G carriers respond better to statins in UCP (significant) and HVH (not significant).
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