Transforming the logistics of liver transplantation with normothermic machine perfusion: Clinical impact versus cost.

Normothermic machine perfusion (NMP) facilitates utilization of marginal liver allografts. It remains unknown whether clinical benefits offset additional costs in the real-world setting. We performed a comparison of outcomes and hospitalization costs for donor livers preserved by NMP versus static cold storage (SCS) at a high-volume center.

Bilateral Renal Auto-Transplantation for Retroperitoneal Sarcomas: Is It Underutilized?

Sarcomas are a rare tumor of mesenchymal origin. The liposarcoma is the most common sarcoma of the retroperitoneum. Liposarcomas are typically low grade, and present at an advanced stage and a large size.

Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion.

Unlabelled: Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver.

Evaluation of Interleukin 6(Il-6), Tumor Necrosis Factor Alpha (Tnf-α) and Paraoxonase 1(Pon 1) in Obese and Non-Obese Metabolic Syndrome.

Unlabelled: Metabolic syndrome is a multiplex of the risk factor for the development of type 2 diabetes and cardiovascular disease and it reflects the clustering of multiple risk factors resulting from obesity and insulin resistance. Despite its predominance in obese individuals, MS does occur in non-obese individuals. Many individuals characterized as normal weight as per their body mass index (BMI), have increased visceral adiposity thereby leading to an unfavorable inflammatory cytokine profile and altered PON levels.

Two Compartment Evaluation of Liver Grafts During Acellular Room Temperature Machine Perfusion (acRTMP) in a Rat Liver Transplant Model.

Background: Subnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability.

Medicinal chemistry strategies to extend duration of action of inhaled drugs for intracellular targets.

Prolonging duration of action of inhaled drugs is a challenging endeavor and guidance for medicinal chemistry teams is very limited, particularly if the site of action is intracellular. Herein, we identified recent literature reports of newly designed inhaled compounds with intracellular targets and summarized learnings from different approaches and strategies undertaken by medicinal chemistry teams. We highlight key properties that have shown to lead to longer duration of action and provide guidance on the best strategy to follow while designing a new inhaled drug with an intracellular target.

Anti-thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival.

Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression.

Coagulation, inflammation, and CD46 transgene expression in neonatal porcine islet xenotransplantation.

Background: Thrombosis is a known consequence of intraportal islet transplantation, particularly for xenogeneic islets. To define the origins of thrombosis after islet xenotransplantation and relate it to early inflammation, we examined porcine islets transplanted into non-human primates using a dual-transplant model to directly compare islet characteristics.

Methods: α1,3-Galactosyltransferase gene-knockout (GTKO) islets with and without expression of the human complement regulatory transgene CD46 (hCD46) were studied.

The folded, bipaddled pectoralis major myocutaneous flap for complex oral cavity defects: Undiminished relevance in the era of free flaps.

Oral cancer often presents at an advanced stage, requiring extensive resection and complex reconstruction, such as free tissue transfers, which may not be available in a remote or resource-constrained facility. The common alternative in these cases is the use of the workhorse flap, the pectoralis major myocutaneous (PMMC) flap for lining and a second regional flap for cover. The results are variable, increase operative time and cost, and may cause additional donor site morbidity.

Reversible inhibition of efflux transporters by hydrogel microdevices.

Oral drug delivery is a preferred administration route due to its low cost, high patient compliance and fewer adverse events compared to intravenous administration. However, many pharmaceuticals suffer from poor solubility and low oral bioavailability. One major factor that contributes to low bioavailability are efflux transporters which prevent drug absorption through intestinal epithelial cells.

Human intestinal spheroids cultured using Sacrificial Micromolding as a model system for studying drug transport.

In vitro models of the small intestine are crucial tools for the prediction of drug absorption. The Caco-2 monolayer transwell model has been widely employed to assess drug absorption across the intestine. However, it is now well-established that 3D in vitro models capture tissue-specific architecture and interactions with the extracellular matrix and therefore better recapitulate the complex in vivo environment.

The role of human CD46 in early xenoislet engraftment in a dual transplant model.

Background: Membrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing CD46 have been shown to resist hyperacute rejection. However, the incremental value of human CD46 expression for islet xenotransplantation remains poorly defined.

Recent advances in intraocular sustained-release drug delivery devices.

Topical eye-drop administration and intravitreal injections are the current standard for ocular drug delivery. However, patient adherence to the drug regimen and insufficient administration frequency are well-documented challenges to this field. In this review, we describe recent advances in intraocular implants designed to deliver therapeutics for months to years, to obviate the issues of patient adherence.

Secondary lymphoid tissue and costimulation-blockade resistant rejection: A nonhuman primate renal transplant study.

Naïve T cell activation requires antigen presentation combined with costimulation through CD28, both of which optimally occur in secondary lymphoid tissues such as lymph nodes and the spleen. Belatacept impairs CD28 costimulation by binding its ligands, CD80 and CD86, and in doing so, impairs de novo alloimmune responses. However, in most patients belatacept is ineffective in preventing allograft rejection when used as a monotherapy, and adjuvant therapy is required for control of costimulation-blockade resistant rejection (CoBRR).

Circulating mitochondria in organ donors promote allograft rejection.

The innate immune system is a critical regulator of the adaptive immune responses that lead to allograft rejection. It is increasingly recognized that endogenous molecules released from tissue injury and cell death are potent activators of innate immunity. Mitochondria, ancestrally related to bacteria, possess an array of endogenous innate immune-activating molecules.

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

Purpose: We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo.

Methods: Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ∼40 and 20 μm for timolol and brimonidine compartments, respectively.

Corrigendum to "The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation".

[This corrects the article DOI: 10.1155/2017/8415205.].

Early barriers to neonatal porcine islet engraftment in a dual transplant model.

Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the poorly understood instant blood-mediated inflammatory reaction and a thorough understanding of early xeno-specific immune responses.

The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation.

Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials.