Contemporary Use of Venoarterial Extracorporeal Membrane Oxygenation: Insights from the Multicenter RESCUE Registry

BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a life-saving therapy for patients with cardiovascular collapse, but identifying patients unlikely to benefit remains a challenge.Methods and ResultsWe created the RESCUE registry, a retrospective, observational registry of adult patients treated with VA-ECMO between January 2007 and June 2017 at 3 high-volume centers (Columbia University, Duke University, and Washington University) to describe short-term patient outcomes. In 723 patients treated with VA-ECMO, the most common indications for deployment were postcardiotomy shock (31%), cardiomyopathy (including acute heart failure) (26%), and myocardial infarction (17%). Patients frequently suffered in-hospital complications, including acute renal dysfunction (45%), major bleeding (41%), and infection (33%). Only 40% of patients (n = 290) survived to discharge, with a minority receiving durable cardiac support (left ventricular assist device [n = 48] or heart transplantation [n = 7]). Multivariable regression analysis identified risk factors for mortality on ECMO as older age (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12–1.42) and female sex (OR, 1.44; 95% CI, 1.02–2.02) and risk factors for mortality after decannulation as higher body mass index (OR 1.17; 95% CI, 1.01-1.35) and major bleeding while on ECMO support (OR, 1.92; 95% CI, 1.23–2.99).ConclusionsDespite contemporary care at high-volume centers, patients treated with VA-ECMO continue to have significant in-hospital morbidity and mortality. The optimization of outcomes will require refinements in patient selection and improvement of care delivery.     

Application of disaccharides alone and in combination,for the improvement of stability and particle properties of spray-freeze dried IgG

Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD.

Methods: Induced soluble aggregates were quantified at 0 and 3?months, and 45?°C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy.

Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12?µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage.

Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules.     

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol

International Urology and Nephrology - The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy...     

A comprehensive non‐invasive framework for automated evaluation of acute renal transplant rejection using DCE‐MRI

The objective was to develop a novel and automated comprehensive framework for the non‐invasive identification and classification of kidney non‐rejection and acute rejection transplants using 2D dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). The proposed approach consists of four steps. First, kidney objects are segmented from the surrounding structures with a geometric deformable model. Second, a non‐rigid registration approach is employed to account for any local kidney deformation. In the third step, the cortex of the kidney is extracted in order to determine dynamic agent delivery, since it is the cortex that is primarily affected by the perfusion deficits that underlie the pathophysiology of acute rejection. Finally, we use an analytical function‐based model to fit the dynamic contrast agent kinetic curves in order to determine possible rejection candidates. Five features that map the data from the original data space to the feature space are chosen with a k‐nearest‐neighbor (KNN) classifier to distinguish between acute rejection and non‐rejection transplants. Our study includes 50 transplant patients divided into two groups: 27 patients with stable kidney function and the remainder with impaired kidney function. All of the patients underwent DCE‐MRI, while the patients in the impaired group also underwent ultrasound‐guided fine needle biopsy. We extracted the kidney objects and the renal cortex from DCE‐MRI for accurate medical evaluation with an accuracy of 0.97 ± 0.02 and 0.90 ± 0.03, respectively, using the Dice similarity metric. In a cohort of 50 participants, our framework classified all cases correctly (100%) as rejection or non‐rejection transplant candidates, which is comparable to the gold standard of biopsy but without the associated deleterious side‐effects. Both the 95% confidence interval (CI) statistic and the receiver operating characteristic (ROC) analysis document the ability to separate rejection and non‐rejection groups. The average plateau (AP) signal magnitude and the gamma‐variate model functional parameter α have the best individual discriminating characteristics. Copyright © 2013 John Wiley & Sons, Ltd.     

Differential role of RIP1 in Smac mimetic-mediated chemosensitization of neuroblastoma cells

We explored the potential of Smac mimetics, which antagonize Inhibitor of Apoptosis (IAP) proteins, for chemosensitization of neuroblastoma (NB). Here, we report that Smac mimetics, e.g. BV6, prime NB cells for chemotherapeutics including the topoisomerase II inhibitor doxorubicin (DOX) and vinca alkaloids such as Vincristine (VCR), Vinblastine (VBL) and Vinorelbine (VNR). Additionally, BV6 acts in concert with DOX or VCR to suppress long-term clonogenic growth. While BV6 causes rapid downregulation of cellular IAP (cIAP)1 protein and nuclear factor-kappaB (NF-κB) activation, DOX/BV6- or VCR/BV6-induced apoptosis occurs independently of NF-κB or TNFα signaling, since overexpression of dominant-negative IκBα superrepressor or the Tumor Necrosis Factor (TNF)α-blocking antibody Enbrel fail to block cell death. Mechanistic studies reveal that Receptor-interacting protein (RIP)1 is required for DOX/BV6-, but not for VCR/BV6-induced apoptosis, since transient or stable knockdown of RIP1 or the pharmacological RIP1 inhibitor necrostatin-1 significantly reduce apoptosis. By comparison, VCR/BV6-mediated apoptosis critically depends on the mitochondrial pathway. VCR/BV6 cotreatment causes phosphorylation of BCL-2 during mitotic arrest, enhanced activation of BAX and BAK and loss of mitochondrial membrane potential (MMP). Additionally, overexpression of BCL-2 profoundly suppresses VCR/BV6-induced apoptosis. Thus, BV6 sensitizes NB cells to chemotherapy-induced apoptosis via distinct initial signaling mechanisms depending on the chemotherapeutic drug. These findings provide novel mechanistic insights into Smac mimetic-mediated chemosensitization of NB.     

Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: A multi-institutional investigation

Purpose

To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy.