Apheresis in Thoracic Organ Transplantation

The beneficial addition of cyclosporine and tacrolimus to the immunosuppressive armamentarium have unfortunately only partially solved the problems of acute and chronic rejection in thoracic organ transplantation. Apheresis techniques offer creative avenues for modifications of allograft rejection. Plasmapheresis can be used for mechanical reduction of alloantibody burdens in highly sensitized patients and permit transplantation in an otherwise almost hopeless situation and can also be used on a short-term basis for the treatment of acute humoral rejection. Extracorporeal photochemotherapy holds promise as a possibly synergistic adjunct to conventional therapy and may even reduce the severity of graft vasculopathy. The increasing availability of highly specific column immunoadsorption techniques may further increase the applicability of apheresis in transplantation.     

Hyperglycemia and Diabetes Mellitus Following Organ Transplantation

Hyperglycemia is common following organ transplantation, regardless of the pre-transplant diabetes status. Transient post-transplant hyperglycemia and/or new-onset diabetes after transplantation (NODAT) are common and are associated with increased morbidity and mortality. NODAT and type 2 diabetes share similar characteristics, but the pathophysiology may differ. Immunosuppressive agents and steroids play a key role in the development of NODAT. Glycemic control is challenging in this population due to fluctuating renal/end-organ function, immunosuppressive dosing, nutritional status, and drug-drug interactions. A proactive and multidisciplinary approach is essential, along with flexible protocols to adjust to patient status, type of organ transplanted, and corticosteroid regimens. Insulin is the preferred agent for hospitalized patients and during the early post-transplant period; optimal glycemic control (BG?<?180 mg/dl with minimal hypoglycemia [<70 mg/dl]) is desired.     

Pneumatosis Cystoides Intestinalis after Organ Transplantation

Pneumatosis cystoides intestinalis (PCI) is a rare disorder of undetermined etiology which is associated with various medical and gastrointestinal conditions. Fewer than 50 cases of PCI occurring after organ transplantation have been reported in the transplant and surgical literature. All have occurred either after bone marrow, kidney, or liver transplantation. The etiology remains obscure but proposed factors include pretransplantation chemotherapy and radiotherapy, immunosuppressive therapy, graft-versus-host disease, opportunistic enteric infections, and a sympathetic reaction from an adjacent inflamed allograft. The patients are often mildly symptomatic, and asymptomatic pneumoperitoneum is seen not infrequently. If the patient does not have a serious underlying illness, then the prognosis is good, with spontaneous resolution occurring in most cases. We report the first case of PCI occurring after an orthoptic cardiac transplantation, and extensively review the literature of PCI occurring in the setting of organ transplantation. We conclude that PCI is often a benign and self-limited condition in this setting, and morbidity is usually related to another complication of transplantation. Even the presence of pneumoperitoneum usually is not associated with peritonitis, and most cases of PCI can be managed conservatively.     

Effects of Smoking on Solid Organ Transplantation Outcomes

Tobacco smoking is the leading preventable cause of death worldwide. Both donor and recipient smoking have been shown to increase graft loss and mortality in solid organ transplant recipients in many studies. Only in lung transplants is smoking a universal contraindication to transplantation. Transplant centers implement different policies regarding smoking recipients and allografts from smoking donors. Due to scarcity of available allografts, the risks of smoking have to be weighed against the risks of a longer transplant waitlist period. Although transplant centers implement different strategies to encourage smoking cessation pre- and post-transplant, not many studies have been published that validate the efficacy of smoking cessation interventions in this vulnerable population. This article summarizes the results of studies investigating prevalence, impact on outcomes, and cessationinterventions for smoking in the transplant population. We report herein a review of the elevated risks of infection, malignancy, graft loss, cardiovascular events, and mortality in solid organ transplant populations.     

Multidrug-Resistant Bacterial Donor-Derived Infections in Solid Organ Transplantation

Although rare, donor-derived infections (DDIs) caused by multidrug-resistant (MDR) bacteria can have devastating consequences for organ transplant recipients. Recognition of MDR bacterial DDIs can be challenging, as MDR bacteria are prevalent in most hospitals and distinguishing their transmission through transplantation from other, more typical routes of acquisition are difficult. New technologies such as whole genome sequencing have recently proven to be a powerful advance in the investigation of MDR bacterial DDIs. Once recognized, the optimal treatment of MDR bacterial DDIs is not clear. Herein, we review the clinical manifestations, outcomes, and management of MDR bacterial DDIs, and identify areas of uncertainty toward which the transplant community should direct further research efforts.     

Hepatitis C Virus Treatment in Non-Liver Organ Transplantation Programs

Purpose of Review

Solid organ transplantation is the treatment of choice for many patients with end organ damage. Hepatitis C (HCV) infection is prevalent among solid organ candidates and recipients and remains to be a significant source of morbidity and mortality for this population. New therapies are currently available for this population. In the following review, we will outline HCV treatment strategies in non-liver transplantation candidates and recipients.

Recent Findings

Direct-acting antivirals (DAAs) have drastically modified the treatment landscape of HCV. New DAA agents have been studied in patients with chronic diseases, transplantation candidates, and transplantation recipients.

Summary

The safety and efficacy of DAAs in patients awaiting liver transplantation and liver transplantation recipients has provided us with guidance on how to use them effectively for patients who received or are awaiting non-liver solid organ transplantations.

     

New Strategies for BMT,Organ Transplantation,and Regeneration Therapy

Bone marrow transplantation (BMT) is becoming a powerful strategy for the treatment of hematologic disorders, congenital immunodeficiencies, metabolic disorders and also autoimmune diseases.

We have previously found using various animal models for spontaneous autoimmune diseases, that allogeneic bone marrow transplantation (allo BMT) can be used to prevent and treat various autoimmune diseases. In addition, we have found that autoimmune diseases are stem cell disorders. However, in MRL/lpr mice, which are radiosensitive (<8.5 Gy), we found that conventional BMT had only a transient effect on autoimmune diseases, which were found to recur. Therefore, we concentrated on discovering new strategies to prevent and treat autoimmune diseases in the radiosensitive and chimeric-resistant MRL/lpr mouse.

Using MRL/lpr mice, we established a new method for allo BMT. In this method, whole bone marrow cells (BMCs), containing a small number of T cells and mesenchymal stem cells (MSCs), were directly injected into the bone marrow cavity (intra-bone marrow [IBM]-BMT). MRL/lpr mice treated with IBM-BMT survived more than 2 years without showing the symptoms of autoimmune diseases.

To apply this BMT method to humans, we have also established a new method for BMC harvesting using cynomolgus monkeys. In this method, BMCs are harvested from the long bones using a "Perfusion Method" (PM) and the whole BMCs (including MSCs) are then injected directly into the IBM. We believe that this new method will become a powerful strategy for the treatment of various intractable diseases, including age-associated diseases such as osteoporosis.