Prediction, prevention, and management of right ventricular failure after left ventricular assist device implantation: A comprehensive review.

Left ventricular assist devices (LVADs) are increasingly common across the heart failure population. Right ventricular failure (RVF) is a feared complication that can occur in the early post-operative phase or during the outpatient follow-up. Multiple tools are available to the clinician to carefully estimate the individual risk of developing RVF after LVAD implantation. This review will provide a comprehensive overview of available tools for RVF prognostication, including patient-specific and right ventricle (RV)-specific echocardiographic and hemodynamic parameters, to provide guidance in patient selection during LVAD candidacy. We also offer a multidisciplinary approach to the management of early RVF, including indications and management of right ventricular assist devices in this setting to provide tools that help managing the failing RV.

Does the level of socioeconomic deprivation at the location of cardiac arrest in an English region influence the likelihood of receiving bystander-initiated cardiopulmonary resuscitation?

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality. Administration of cardiopulmonary resuscitation (CPR) by a bystander witnessing a cardiac arrest has been shown to increase the likelihood of return of spontaneous circulation and survival. This study analyses the association between the socioeconomic status of the location where a person suffers a cardiac arrest and the proportion of victims with OHCA receiving bystander CPR. METHODS: Retrospective analysis of all OHCAs occurring in North East England from 1 January 2011 to 31 December 2011: data obtained from the North East Cardiac Arrest Network Registry. RESULTS: Of 3179 OHCAs with an attempt at resuscitation, 623 patients received bystander-initiated CPR (19.6%). From quintile (Q) 1 to Q5 (most deprived to least deprived), bystander-initiated CPR rates increased from 14.5% to 23.3% (p for trend <0.001). Patients in the least deprived quintile were significantly more likely to receive bystander-initiated CPR when compared with those in the most deprived quintile (OR=1.78, 95% CI 1.32 to 2.39, p≤0.001). CONCLUSIONS: Increasing socioeconomic status at the location of cardiac arrest is positively associated with the likelihood of bystander CPR for OHCA in this region of England.

Retinal haemorrhages associated with fatal paediatric infections.

For many physicians, retinal haemorrhages (RHs) in infants and young children remain highly diagnostic of non-accidental (abusive) head trauma. Because clinicians have applied indirect ophthalmoscopy selectively to cases of suspected child abuse, the association between RH and other conditions such as infection, coagulopathy and accidental trauma has encountered habitual bias, creating the potential for iatrogenic misdiagnosis of child abuse. We present an autopsy case series of four children, aged three years old or younger, in whom RHs were detected by post-mortem monocular indirect ophthalmoscopy after the patients had died from infections. We discuss the laterality, number, type and location of RHs in these cases, and summarize proposed mechanisms of RH formation in fatalities from paediatric infection. We demonstrate that many of the ophthalmological findings that have been considered diagnostic of abusive head trauma can also occur in association with infective processes.

Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand.

Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine-based approach termed "semi-xenotransplantation" (SX) seeks to overcome these obstacles by combining the availability and reproducibility of animal organs with the biocompatibility and functionality of human allografts. Compared to conventional xenotransplantation wherein the whole organ is animal-derived, SX grafts are cleansed of their antigenic cellular compartment to produce whole-organ extracellular matrix scaffolds that retain their innate structure and vascular channels. These scaffolds are then repopulated with recipient or donor human stem cells to generate biocompatible semi-xenografts with the structure and function of native human organs. While numerous hurdles must be still overcome in order for SX to become a viable treatment option for end-stage organ failure, the immense potential of SX for meeting the urgent needs for a new source of organs and immunosuppression-free transplantation justifies the interest that the transplant community is committing to the field.

Extracellular Matrix Scaffold Technology for Bioartificial Pancreas Engineering: State of the Art and Future Challenges.

Emergent technologies in regenerative medicine may soon overcome the limitations of conventional diabetes therapies. Collaborative efforts across the subfields of stem cell technology, islet encapsulation, and biomaterial carriers seek to produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes. These technologies rely on a robust understanding of the extracellular matrix (ECM), the supportive 3-dimensional network of proteins necessary for cellular attachment, proliferation, and differentiation. Although these functions can be partially approximated by biosynthetic carriers, novel decellularization protocols have allowed researchers to discover the advantages afforded by the native pancreatic ECM. The native ECM has proven to be an optimal platform for recellularization and whole-organ pancreas bioengineering, an exciting new field with the potential to resolve the dire shortage of transplantable organs. This review seeks to contextualize recent findings, discuss current research goals, and identify future challenges of regenerative medicine as it applies to diabetes management.

Cell replacement strategies aimed at reconstitution of the ß-cell compartment in type 1 diabetes.

Emerging technologies in regenerative medicine have the potential to restore the ß-cell compartment in diabetic patients, thereby overcoming the inadequacies of current treatment strategies and organ supply. Novel approaches include: 1) Encapsulation technology that protects islet transplants from host immune surveillance; 2) stem cell therapies and cellular reprogramming, which seek to regenerate the depleted ß-cell compartment; and 3) whole-organ bioengineering, which capitalizes on the innate properties of the pancreas extracellular matrix to drive cellular repopulation. Collaborative efforts across these subfields of regenerative medicine seek to ultimately produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes.

Regeneration and bioengineering of the kidney: current status and future challenges.

The prevalence of chronic kidney disease continues to outpace the development of effective treatment strategies. For patients with advanced disease, renal replacement therapies approximate the filtration functions of the kidney at considerable cost and inconvenience, while failing to restore the resorptive and endocrine functions. Allogeneic transplantation remains the only restorative treatment, but donor shortage, surgical morbidity and the need for lifelong immunosuppression significantly limit clinical application. Emerging technologies in the fields of regenerative medicine and tissue engineering strive to address these limitations. We review recent advances in cell-based therapies, primordial allografts, bio-artificial organs and whole-organ bioengineering as they apply to renal regeneration. Collaborative efforts across these fields aim to produce a bioengineered kidney capable of restoring renal function in patients with end-stage disease.

Considerations on the development of a model of kidney bioengineering and regeneration in rats.

Evaluation of: Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19(5), 646-51 (2013). Emergent technologies of regenerative medicine have shown immense potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered ex vivo in the laboratory. So far, clinical translation has been possible for simple, hollow organs, whereas the bioengineering and regeneration of complex modular organs (namely, kidneys, hearts, livers, lungs and small bowel) remains far from our grasp. In the case of the kidney, the bioengineering and regeneration of renal organoids requires a supporting scaffold that approximates the biochemical, spatial and vascular relationships of the native kidney extracellular matrix. A recent report describes the use of rodent kidneys to generate whole organ, three-dimensional scaffolds. These scaffolds were subsequently seeded with rat neonatal kidney cells to reconstitute the parenchymal cell compartment and with human umbilical venous endothelial cells to reconstitute the endothelium and allow implantation. Once assembled and allowed to mature in bioreactors, the so-obtained constructs were able to exert some function peculiar to the kidney both in vitro and in vivo after implantation in rodents. In this invited commentary, we will address the most critical topics of organ regeneration starting from the above-mentioned experience with the kidney but eventually embracing the whole field of complex modular organs bioengineering.

Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies.

In the United States, more than 2600 kidneys are discarded annually, from the total number of kidneys procured for transplant. We hypothesized that this organ pool may be used as a platform for renal bioengineering and regeneration research. We previously showed that decellularization of porcine kidneys yields renal extracellular matrix (ECM) scaffolds that maintain their basic components, support cell growth and welfare in vitro and in vivo, and show an intact vasculature that, when such scaffolds are implanted in vivo, is able to sustain physiological blood pressure. The purpose of the current study was to test if the same strategy can be applied to discarded human kidneys in order to obtain human renal ECM scaffolds. The results show that the sodium dodecylsulfate-based decellularization protocol completely cleared the cellular compartment in these kidneys, while the innate ECM framework retained its architecture and biochemical properties. Samples of human renal ECM scaffolds stimulated angiogenesis in a chick chorioallantoic membrane assay. Importantly, the innate vascular network in the human renal ECM scaffolds retained its compliance. Collectively, these results indicate that discarded human kidneys are a suitable source of renal scaffolds and their use for tissue engineering applications may be more clinically applicable than kidneys derived from animals.

Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering.

Emergent technologies of regenerative medicine have the potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered in the laboratory. Pancreas bioengineering requires a scaffold that approximates the biochemical, spatial and vascular relationships of the native extracellular matrix (ECM). We describe the generation of a whole organ, three-dimensional pancreas scaffold using acellular porcine pancreas. Imaging studies confirm that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. The scaffold was seeded with human stem cells and porcine pancreatic islets, demonstrating that the decellularized pancreas can support cellular adhesion and maintenance of cell functions. These findings advance the field of regenerative medicine towards the development of a fully functional, bioengineered pancreas capable of establishing and sustaining euglycemia and may be used for transplantation to cure diabetes mellitus.

Regeneration and bioengineering of transplantable abdominal organs: current status and future challenges.

INTRODUCTION: The most critical issue to organ transplantation is the identification of new sources of organs. The present manuscript illustrates the state-of-the-art regenerative medicine (RM) investigations aiming to manufacturing abdominal organs for transplant purposes. AREAS COVERED: This manuscript focuses on research in the bioengineering and regeneration of kidneys, insulin-producing cells, livers and small bowel. The main technology currently under development exploits the seeding of cells on supporting scaffolding material. Despite favorable preliminary results obtained with relatively simple, hollow organs, when more complex organs are considered, the scenario changes dramatically. Investigations are still in early stages, and clinical translation is not yet foreseeable based on current knowledge and information. Obstacles are numerous but we believe the critical factor hampering success is lack of in-depth understanding of the extracellular matrix (ECM) and cell-ECM interactions, as well as the mechanisms with which organs develop in utero. EXPERT OPINION: The success of RM to generate transplantable abdominal organs relies heavily on progress in (stem) cell therapies, developmental and ECM biology, and in the thorough understanding of the intricate relationship and interplay between cells and the ECM. This will require enormous investments in financial and medical resources, which ideally should be embarked upon by governments, the private sector and academia.

Fatal subarachnoid hemorrhage following traumatic rupture of the internal carotid artery.

Traumatic subarachnoid hemorrhage (TSAH) is a life-threatening intracranial bleed often associated with violent assault or motor vehicle accidents. The vast majority of TSAH is associated with rupture of the vertebral artery, although rare cases of traumatic aneurysm of the internal carotid artery (ICA) have been reported. A 27-year-old man was found bleeding and unresponsive following a violent altercation in which he received repeated blows to the head and neck. CT scan showed acute SAH, and death ensued within 24 h. Autopsy revealed generalized bruising of the face, a complete midline mandibular fracture, and massive basal SAH resulting from traumatic rupture of the right terminal internal carotid artery at the origin of the middle cerebral artery. Anterior and posterior neck dissection revealed focal hemorrhage associated with the right neural arch of the first cervical vertebra (C1). Autopsy findings were consistent with TSAH resulting from rupture of the ICA following blunt force trauma to the head. The rupture site in TSAH can be difficult to locate, and injury to the ICA may be overlooked if not routinely examined. Dissection of the neck and skull base is required to ensure accurate identification of the site of vascular injury.