Author Interviews, Infections, Transplantation / 28.09.2015

MedicalResearch.com Interview with: Dr. Wilfried Gwinner Div. of Nephrology and Hypertension University of Hanover Medical School HannoverDr. Wilfried Gwinner Div. of Nephrology and Hypertension University of Hanover Medical School Hannover and Dr. Uta Erdbruegger Div. Nephrology and Hypertension Division University of Virginia, Charlottesville Dr. Uta Erdbruegger Div. Nephrology and Hypertension Division University of Virginia, Charlottesville   Medical Research: What is the background for this study? What are the main findings? Dr. Erdbruegger: Controversy exists whether CMV infections or viremia after kidney transplantation affect patient and graft survival. We aimed to explore the role of CMV in a retrospective study on almost 600 patients followed at our transplant center over a period of up to 10 years post-transplant. The analysis included protocol biopsy findings and causes for graft failure and death. We observed reduced patient and graft survival in patients with CMV as reported in some of the previous studies. However, we found that patients with CMV had an inferior kidney function and significant chronic allograft changes in the biopsies very early after transplantation – even before the CMV infection. Also, CMV infection was not specifically related to a progression of chronic changes. On the other hand, we confirmed well-established factors like inferior graft function early on, delayed graft function, and higher donor and recipient age as important for patient and graft survival. In none of these analyses, CMV was a significant factor. In summary, this suggests that CMV is rather an epiphenomenon. Alternatively, we might have missed a possible small effect of CMV in our statistics. In any case, our results do not support a significant role of CMV in patient and graft outcomes. (more…)
Author Interviews, Emory, JAMA, Kidney Disease / 11.08.2015

Rachel Patzer, PhD, MPH Director of Health Services Research, Emory Transplant Center Assistant Professor Department of Surgery Division of Transplantation Emory University School of MedicineMedicalResearch.com Interview with: Rachel Patzer, PhD, MPH Director of Health Services Research, Emory Transplant Center Assistant Professor Department of Surgery Division of Transplantation Emory University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Patzer: There are two main treatments for patients with end stage kidney disease: dialysis or kidney transplantation.  Kidney transplantation offers the best survival and quality of life compared to dialysis.  However, there is a limited supply of organs in the U.S., so not all patients with end stage organ failure get a kidney transplant. Certain regions of the country have lower access to kidney transplantation than other regions.  The Southeastern United States (GA, NC, and SC) has the lowest rates of kidney transplantation in the nation, and Georgia (GA) is the state that ranks at the very bottom. Our research team and collaborators from the Southeastern Kidney Transplant Coalition sought to examine some of the reasons for why Georgia had the lowest rates of kidney transplantation in the nation.  The transplant centers in our Coalition collaborated to share data on patient referrals from dialysis facilities, where the majority of end stage renal disease patients receive treatment, to transplant centers in Georgia. Referral from a dialysis facility to a transplant center is required for patients to undergo the extensive medical evaluation that is required for a patient to either be placed on the national deceased donor waiting list, or to receive a living donor kidney transplant (e.g. from a friend or family member). There were several major findings: 1)    That overall, referral of patients from a dialysis facility to a kidney transplant center is low (only about 28% of patients with kidney failure are referred to a transplant center within a year of starting dialysis). 2)    There was much variation in referral for transplantation across dialysis facilities in GA, where some facilities referred no patients within a year, and others referred up to 75% of their patient population. (more…)
Author Interviews, Biomarkers, Transplantation / 29.05.2015

MedicalResearch.com Interviews with: Dr. Sunil M. Kurian Ph.D.Lead- Biomarker Discovery at the Laboratory of Functional Genomics and Cell Therapy The Scripps Research Institute and Transplant Genomics Inc.Dr. Sunil M. Kurian Ph.D. Lead- Biomarker Discovery at the Laboratory of Functional Genomics and Cell Therapy The Scripps Research Institute and Transplant Genomics Inc. and   Dr. John J. Friedewald, MDAssociate Professor of Medicine and Surger Northwestern University’s Feinberg School of Medicine and a transplant nephrologist at Northwestern Memorial Hospital and the Kovler Organ Transplant CenterDr. John J. Friedewald, MD Associate Professor of Medicine and Surgery Northwestern University’s Feinberg School of Medicine and a transplant nephrologist at Northwestern Memorial Hospital and the Kovler Organ Transplant Center Editor’s note: These interviews are based on two abstracts presented at the American Transplant Congress 2015. MedicalResearch: What is the background for these studies? Response: Previous studies by the scientific founders of Transplant Genomics Inc. helped lay the groundwork for the company’s development of genomic biomarker tests for kidney transplant graft status and demonstrated feasibility as noninvasive monitoring tools that could enable differential diagnosis of graft status in kidney transplant recipients.1-3 These included a study involving five transplant centers published in the American Journal of Transplantation.4 In that study, peripheral blood gene expression profiling was used to classify kidney graft recipients into three key categories of graft status based on gene expression signatures – clinical acute rejection, acute dysfunction no rejection, and stable graft performance - with very high predictive accuracy. STUDY A: Validation of Blood and Biopsy Gene Expression-Based Molecular Diagnostics for Subclinical Acute Rejection: Comparing DNA Microarrays vs. Next-Generation RNA Sequencing  MedicalResearch: What are the main findings? Response: The current study presented recently at the 2015 American Transplant Congress5 validated that gene expression signatures as indicators of kidney graft status can be detected as robustly with RNA sequencing as with microarrays, with implications for reduced cost of analysis, faster turnaround times and improved throughput for sample processing. In this study, we substantiated RNA sequencing as an alternative data generation platform for analyzing gene expression profiles in peripheral blood and tissue from kidney transplant recipients. The data validated that gene expression signatures for subclinical acute rejection (a histological acute cellular rejection in the presence of a normal or stable serum creatinine that is associated with decreased graft survival), clinical acute rejection and stable graft performance can be detected as robustly with RNA sequencing as with microarrays. MedicalResearch: What should clinicians and patients take away from your report? Response: The key point of this study is that gene expression profiles generated and validated using microarray technology have been successfully translated to a technology platform based on RNA sequencing. Sequencing has the potential to offer advantages such as reduced cost of analysis, faster reporting back to the clinician and improved throughput for sample processing. In addition, it could facilitate development of kits enabling standardized assay performance on local lab-based sequencing systems and expansion of test use worldwide. (more…)
Author Interviews, Gastrointestinal Disease, Transplantation, University of Pennsylvania / 11.05.2015

MedicalResearch.com Interview with: Dr. David Goldberg MD, MSCE Assistant Professor of Medicine LDI Fellow, Leonard Davis Institute, University of Pennsylvania Medical Director for Living Donor Liver Transplantation, Hospital of the University of Pennsylvania Senior Scholar, Center for Clinical Epidemiology and Biostatistics MedicalResearch: What is the background for this study? What are the main findings? Dr. Goldberg: While there are data that demonstrate differences in authorization (consent) rates for deceased donation among racial and ethnic minorities, it is unknown how these differences contribute to geographic differences in the number of deceased organ donors.  It has been postulated that geographic differences in the distribution of racial and ethnic minorities may contribute to differences in the deceased organ supply, yet there have been no empiric data to support this.  Using data on “eligible deaths,” defined as potential brain-dead organ donors <=70 years of age, we demonstrated that even after accounting for differences in the racial/ethnic demographics of the potential donor population, there are dramatic differences in authorization (consent) rates across geographic areas that are not explained by demographics alone. If the source of these differences could be identified, then there could be large increases in the number of organ donors, and lifesaving transplants, in areas with lower authorization rates. (more…)
Author Interviews, Transplantation / 20.09.2014

James J. Yoo, M.D., Ph.D. Professor, Institute for Regenerative Medicine Office of Women in Medicine and Science Physiology & Pharmacology Translational Science Institute Wake Forest School of Medicine Winston-Salem, NCMedicalResearch.com Interview with: James J. Yoo, M.D., Ph.D. Professor, Institute for Regenerative Medicine Office of Women in Medicine and Science Physiology & Pharmacology Translational Science Institute Wake Forest School of Medicine Winston-Salem, NC Medical Research: What are the main findings of the study? Dr. Yoo: Our research is part of a long-term effort to engineer replacement kidneys in the lab to help solve the shortage of donor organs. In this particular report, we worked with human-sized kidneys and developed a method to help keep blood vessels in the new organs open and flowing with blood. Until now, lab-built kidneys had been rodent-sized and functioned for only one or two hours after transplantation because blood clots developed. Our method to minimize clot formation involved two steps. First, we identified the most effective way to coat the vessels of the kidney scaffold with endothelial cells. We found that infusing cells with a syringe, followed by a period of pumping cells through the vessels at increasing flow rates, was most effective. Next, we looked for a way to ensure that the cells we introduced actually stayed in the vessels and did not wash away when blood flow was initiated. For this, we coated the vessel walls with an antibody to make them bind the endothelial cells. (more…)
Author Interviews, JAMA, Surgical Research, Transplantation / 17.09.2014

Darren J. Malinoski, MD, FACS Assistant Chief of Surgery – Research and Education Chief, Section of Surgical Critical Care Portland VA Medical Center Associate Professor of Surgery Oregon Health & Science University Portland, OR 97207MedicalResearch.com Interview with: Darren J. Malinoski, MD, FACS Assistant Chief of Surgery – Research and Education Chief, Section of Surgical Critical Care Portland VA Medical Center Associate Professor of Surgery Oregon Health & Science University Portland, OR 97207 Medical Research: What are the main findings of the study?  Dr. Malinoski: Our two main findings are that the status of the DMG Bundle prior to organ recovery, at the end of the OPO donor management process, is the most predictive of the number of organs that will be transplanted per expanded criteria donor (ECD) and that the absolute increase in the number of individual DMG elements achieved over time also appears to be relevant.  Taken together, these two findings suggest that the number of organs that will be transplantable from each donor is not necessarily predetermined by their age, comorbidities, and pre-neurologic death condition, but that active critical care management has the ability to affect outcomes and reassessing each donor’s condition over time is necessary. (more…)
Author Interviews, Hematology, NEJM, Sloan Kettering, Transplantation / 31.07.2014

MedicalResearch.com Interview with: Richard J. O'Reilly, MD Memorial Sloan Kettering Cancer Center Medical Research: What are the main findings of the study? Dr. O'Reilly: 1.       In a comparison of the results of HLA-matched sibling transplants with other established transplant approaches, including T-cell depleted half-matched parental marrow grafts, unmodified transplants from matched unrelated donors and cord blood transplants in the current era (2000-2009), transplants from donors other than HLA-matched siblings had 5 year survival outcomes similar to those of matched siblings when applied to young infants (≤ 3.5 months of age) or infants of any age that were not infected at the time of transplants. Thus any child born with SCID can now be successfully transplanted. 2.       Active infection at the time of transplant significantly reduced chances of long-term survival for all infants except those who received transplants from HLA-matched siblings. Thus, infection is a dominant determinant of transplant outcome.  Control of treatable infections prior to transplant should be a major clinical objective. 3.       Treatment with chemotherapy containing busulfan significantly enhances the likelihood of recovering a normal ability to make antibodies and fosters better recovery of T-cells that provide cell mediated immunity, and may be an acceptable risk in uninfected infants. However, use of any chemotherapy prior to transplant in an infant who is infected, greatly decreases chances of survival. In infected patients who lack a matched sibling, T-cell depleted transplants from half matched related donors had the best outcomes. (more…)