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, Hepatitis - Liver Disease, Transplantation / 04.05.2015

MedicalResearch.com Interview with: Dr. Audrey Coilly MD Fellow at the Centre Hepato-Biliaire Paul Brousse Hospital Villejuif, France Medical Research: What is the background for this study? What are the main findings? Dr. Coilly: ​ Hepatitis C (HCV) recurrence used to be a major issue during two decades for patients transplanted with an active HCV infection at the time of transplantation impacting both patient and graft survival. The combination of sofosbuvir and daclatasvir has not been studied after liver transplantation. The main findings are a high efficacy profile with an overall SVR12 rate of 95%. The safety profile is also good​. The most frequent adverse event is anemia, particularly when ribavirin is still used. (more…)
HIV, Kidney Disease, NEJM, Transplantation / 11.02.2015

Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa MedicalResearch.com Interview with: Elmi Muller, M.B., Ch.B., M.Med. University of Cape Town–Surgery Groote Schuur Hospital Observatory Cape Town Cape Town, South Africa Medical Research: What is the background for this study? Dr. Muller: South Africa currently offers dialysis and transplantation as a treatment option for patients with End Stage Renal Disease (ESRD). However, dialysis is not freely available to everyone, but severely limited and only available to a selected group of patients. This means that patients get assessed when they present with ESRD and they only get accepted onto a dialysis programme if they fulfill certain criteria. These criteria are criteria to assess the patient’s medical fitness in general as well as social criteria to assess whether the patient will be compliant with follow-up.  In most state hospitals, patients will only be accepted onto a dialysis program if they are also fit to receive a transplant in the long run.  The idea is that dialysis programs should naturally feed into transplant programs. Therefore a patient who is not a suitable transplant candidate will normally be turned down for dialysis. In 2008, when the HIV positive-to-positive program started, patients with ESRD and HIV would be turned down for dialysis. The reason was that they were seen as unfit for transplantation and therefore not suitable dialysis patients. This meant that anybody with HIV and ESRD was doomed to die. This situation remained unchallenged for a number of years, especially as the rollout of antiretroviral therapy was quite slow in the state sector. Because of very high HIV rates in the country, more and more HIV positive brain-dead donors presented to the Groote Schuur Hospital Transplant team. These donors were mostly braindead people who were worked up for organ donation (after consent was obtained from the family) and who then turned out to be HIV positive. In 2008 it made sense to try and marry this supply of donors with the group of HIV positive patients without any treatment options in the country. (more…)
Radiology, Transplantation / 01.12.2014

Frank J. Rybicki, MD PhD Director, Applied Imaging Science Laboratory Director, Cardiac CT and Vascular CT / MRI Brigham and Women's Hospital Associate Professor, Harvard Medical School Boston, MAMedicalResearch.com Interview with Frank J. Rybicki, MD PhD Director, Applied Imaging Science Laboratory Director, Cardiac CT and Vascular CT / MRI Brigham and Women's Hospital Associate Professor, Harvard Medical School Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Rybicki: Face transplantation restores form and function to patients with catastrophic facial injuries. To date, surgical planning a vascular anastamoses have been well described. While all 7 patients at BWH have had 3d printed models from their CT scans, to date the findings and impact of 3D printing has not been described. Also, the role of printing the soft tissues of the face has not been described. (more…)
Kidney Disease, Transplantation / 15.11.2014

Anthony Bleyer, Jr. Wake Forest University Class of 2015, Economics President, Club Sports Union Senior Captain, Wake Forest Men's Ultimate MedicalResearch.com Interview with: Anthony Bleyer, Jr.  Wake Forest University Class of 2015, Economics President, Club Sports Union Senior Captain, Wake Forest Men's Ultimate Medical Research: What is the background for this study? What are the main findings? Response: There are over 100,000 individuals waiting for a kidney transplant, but each year only approximately 6,000 individuals have living donors who donate them a kidney; the rest of the individuals must remain on dialysis until they receive a kidney from an individual who has died and is a kidney donor.  A major limiting factor for kidney donation is that many individuals are not healthy enough to donate a kidney because they have  excessive obesity, diabetes mellitus, blood pressure that is too high, or they have other health conditions.  While it was known that obesity, hypertension, and other health conditions are contraindications to kidney transplant, there was no data about what percentage of the US population would be able to donate a kidney.  To study this, we (a team of kidney doctors and researchers at Wake Forest School of Medicine, Winston-Salem, NC) analyzed data from the National Health and Nutrition Survey. This study is a population-based sample that is representative of the US population. Based on data from this study, we determined that 55.2% of the U.S. population would not have met eligibility criteria for kidney donation, often due to preventable health conditions.  19.2% of the population would have been unable to donate due to hypertension, 15% due to obesity, 11.6% due to excessive alcohol intake, and 11.5% due to diabetes.  60.1% of individuals with an adjusted family household income (AFHI) <$35,000 did not meet eligibility criteria vs. 49.3% for an AFHI > $100,000.   If one considers non-US citizenship and a family income below the poverty threshold as exclusion criteria, 68.5% of the US population would be unable to donate. (more…)
Author Interviews, General Medicine, Leukemia, NEJM, Transplantation / 03.11.2014

John E. Wagner, M.D. Principal Investigator Professor Director, Division of Blood and Marrow Transplantation Department of Pediatrics McKnight Presidential Endowed Chair Hageboeck Family / Children's Cancer Research Fund Endowed Chair University of Minnesota Minneapolis, MN 55455MedicalResearch.com Interview with: John E. Wagner, M.D. Principal Investigator Professor Director, Division of Blood and Marrow Transplantation Department of Pediatrics McKnight Presidential Endowed Chair Hageboeck Family / Children's Cancer Research Fund Endowed Chair University of Minnesota Minneapolis, MN 55455 Medical Research: What is the background for this study? What are the main findings? Dr. Wagner: Earlier studies of umbilical cord blood transplantation (UCB) in children with hematological malignancies demonstrated a survival rate of approximately 50%.  While single UCB transplant was very effective despite HLA mismatch, few adults had access to umbilical cord blood as a treatment option due to the cell dose requirement of 2. 5 x 10^6 nucleated cells per kilogram recipient body weight.  For this reason, at the University of Minnesota we explored the co-transplantation of two partially HLA matched umbilical cord blood units in adults as a straightforward strategy to achieving the cell dose requirement.  Early results were remarkable with survival rates higher than that observed in children.  This in turn led to the design of the BMT CTN 0501 study, a randomized trial comparing single versus double umbilical cord blood transplantation in children aged 2-21 years with hematological malignancies.  All patients received a uniform conditioning regimen of fludarabine, cyclophosphamide and total body irradiation and GVHD prophylaxis of cyclosporine A and mycophenylate mofetil.  224 patients were randomized. There were four major findings:
  • 1) survival results overall, regardless of treatment arm, have improved,
  • 2) for children, an adequately dosed single umbilical cord blood unit is sufficient, giving a survival result of 72% at one year,
  • 3) double umbilical cord blood transplant is associated with more GVHD and poorer platelet recovery but survival is comparable to an adequately dosed single unit, and
  • 4) HLA mismatch is well tolerated with potentially better disease free survival in patients transplanted with HLA mismatched umbilical cord blood , a provocative finding that requires further investigation.
(more…)
Author Interviews, Exercise - Fitness, Transplantation / 15.10.2014

MedicalResearch.com Interview with: Elvira Cicognani PhD Department of Psychology School of Psychology and Education, University of Bologna Piazza Aldo Moro, 90 - Cesena, Italy - Viale Berti Pichat, 5 - Bologna, Italy Medical Research: What are the main findings of the study? Dr. Cicognani: The study is part of a larger project of the Italian National Transplant Center (Centro Nazionale Trapianti, CNT), started in 2008, in collaboration with Istituto Superiore di Sanità, Centro Studi Isokinetic, University of Bologna, Cimurri Impresa e Sport and Patients’ associations. The general aim is to encourage transplant patients to practice physical activity and even sport activity, in view of its benefits in enhancing recovery and quality of life after transplantation. In this study we assessed Health-related quality of life on 118 active kidney transplant patients practicing different sports at low to moderate intensity and compared them with those of 79 sedentary kidney transplant patients and with 120 active healthy control subjects. Active transplant patients reported higher levels of quality of life than sedentary patients on most dimensions of quality of life and similar to active healthy controls. In brief, practicing sports may allow patients to achieve a level of quality of life similar to the general population of active individuals. (more…)
Author Interviews, Transplantation / 09.10.2014

Stan Rose, PhD President & CEO of Transplant Genomics Dr. Rose is also a kidney transplant recipientMedicalResearch.com Interview with: Stan Rose, PhD President & CEO of Transplant Genomics Dr. Rose is also a kidney transplant recipient MedicalResearch: What is the background for these studies?  Dr. Rose: The studies by the founding scientists of Transplant Genomics (TGI) presented at the World Transplant Congress (WTC) 2014 represent years of work by our scientific founders and their collaborators at leading institutions in their search for  minimally invasive diagnostic and monitoring tools enabling earlier and more accurate detection and characterization of graft injury in organ transplant recipients. In kidney transplant recipients, for example, current methods consist of tracking creatinine levels and periodic direct assessment of grafts through biopsies. But by the time creatinine levels are elevated, more than 50% of kidney function may be lost. Biopsies, considered the gold standard for assessing graft status, are invasive, risky, unsuited for serial monitoring, and yield inconclusive results as often as 30% of the time. Transplant Genomics is addressing the need for better monitoring by developing a peripheral blood test for genomic biomarkers of transplant graft status to detect early signs of graft injury, differentiate between actionable causes and enable optimization of immunosuppressive therapy. (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, Dermatology, JAMA, NIH, Transplantation / 11.09.2014

MedicalResearch.com Interview with: Rena Zuo, BA MD Candidate at Duke University School of Medicine and Edward W. Cowen, MD, MHSc Senior Clinician Head, Dermatology Consultation Service Dermatology Branch Center for Cancer Research National Cancer Institute National Institutes of Health MedicalResearch: What are the main findings of the study?
 Answer: Chronic graft-vs-host disease (cGVHD) is a debilitating multisystem disease that occurs in patients receiving allogeneic hematopoietic stem cell transplantations as treatment for hematologic disorders. Although the diverse clinical presentations of cGVHD frequently mimic other autoimmune diseases such as Sjögren syndrome and systemic sclerosis, and low-titer antibodies are commonly found in patients with cGVHD, the exact pathogenesis and role of autoimmunity in cGVHD are incompletely understood. Our study is the first to characterize and identify risk factors associated with the development of two uncommon autoimmune phenomena, specifically alopecia areata and vitiligo, in the setting of cGVHD. Laboratory markers, including 11 antibodies, transplant-related factors, and other cGVHD systemic manifestations were analyzed. Several particularly interesting results were found:
  1. Among 282 patients with cGVHD, 15 demonstrated vitiligo (14 of 282; 4.9%) and/or alopecia areata (2 of 282; 0.7%).
  2. Female donor and female donor to male recipient sex mismatch, in particular, are significantly associated with the development of vitiligo and/or alopecia areata.
  3. Positive anti-cardiolipin (ACA) IgG was also significantly associated with development of vitiligo and/or alopecia areata.
(more…)
Author Interviews, Transplantation / 22.08.2014

Alvaro Rojas-Pena, MD Research Investigator, Laboratory Coordinator Robert H. Bartlett – Extracorporeal Life Support Laboratory Department of Surgery, Section of Transplantation Surgery Ann Arbor, MI 48109MedicalResearch.com Interview with:  Alvaro Rojas-Pena, MD Research Investigator, Laboratory Coordinator Robert H. Bartlett – Extracorporeal Life Support Laboratory Department of Surgery, Section of Transplantation Surgery Ann Arbor, MI 48109 Medical Research: What are the main findings of the study? Dr. Rojas-Pena: During the first 10 years’ experience of the University of Michigan using Extracorporeal Support (ECS) for organ donation in controlled donors after circulatory determination of death (cDCDD) we were able to increase the pool of organs suitable for transplantation by 20%. A total of 48 renal grafts, 13 livers and 1 pancreas were successfully transplanted from 37 cDCDD. Kidneys transplanted after extracorporeal support assisted donation had a delayed graft function (DGF) rate of 31%, compared to the rate of renal grafts procured without extracorporeal support (64%).  DGF was defined as the need of hemodialysis within the first 7 days post transplantation Finally, the 3-year survival rate of the renal transplant recipients is within the national standard for all renal recipients of cDCD at our institution. (more…)
Author Interviews, Colon Cancer, JAMA, Transplantation / 15.08.2014

MedicalResearch.com Interview with: Øyvind Holme, MD Department of Medicine, Sorlandet Hospital Kristiansand, Kristiansand, Norway Institute of Health and Society, University of Oslo, Oslo, Norway Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Harvard-MIT Division of Health Sciences and Technology Boston, Massachusetts Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway Medical Research: What are the main findings of the study? Dr. Holme: In this population-based trial, we found that once-only flexible sigmoidoscopy screening in asymptomatic 50-64 year old individuals reduces colorectal cancer mortality by 27% and colorectal cancer incidence by 20% after 11 years of follow-up. We found that the incidence reduction is as great in 50-54 year old individuals as in 55-64 old individuals. Addition of a once-only fecal occult blood test to flexible sigmoidoscopy did not lead to a larger reduction in colorectal cancer incidence or mortality compared to flexible sigmoidoscopy screening alone. (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…)
Author Interviews, Kidney Disease, Lancet, Transplantation / 28.07.2014

MedicalResearch.com Interview with Dr. Richard Haynes Clinical Trial Service Unit and Epidemiological Studies Unit Roosevelt Drive, Headington Oxford OX3 Medical Research: What are the main findings of the study? Dr. Haynes: The main result from this analysis is that alemtuzumab-based induction therapy (ie, alemtuzumab followed by low-dose mycophenolate and tacrolimus with steroid avoidance) reduced biopsy-proven acute rejection by about half during the first 6 months after transplantation among a wide variety of different types of participant, compared to standard basiliximab-based induction therapy (basiliximab followed by standard dose mycophenolate, tacrolimus and steroids). This reduction was achieved despite the lower doses of tacrolimus used and there was no excess of infection observed. (more…)
Author Interviews, Gender Differences, Heart Disease, JACC, Transplantation / 25.07.2014

Dr. Eileen Hsich MD Director of the Women’s Heart Failure Clinic Associate Medical Director for the Heart Transplant Program Cleveland Clinic, Cleveland, OhioMedicalResearch.com Interview Invitation  Dr. Eileen Hsich MD Director of the Women’s Heart Failure Clinic Associate Medical Director for the Heart Transplant Program Cleveland Clinic, Cleveland, Ohio Medical Research: What are the main findings of the study? Dr. Hsich: Women are dying on the heart transplant waiting list at a faster rate than men for almost a decade (see Figure 1) and few studies have even addressed this problem. The occurrence is largely driven by gender differences in survival at the most urgent status (UNOS Status 1A) but the cause remains unclear. Although data is limited our findings raise concern that women are not successfully bridged to transplantation while they remain at high status and are inactivated due to worsening condition. Figure 1. Scientific Registry of Transplant Recipients: Mortality on Waiting List For Heart Transplantation Heart waiting list by gender 2000-2009   Figure derived from table in Scientific registry of transplant recipients: Heart waiting list by gender 2000-2009. Available at: Http://srtr.Transplant.Hrsa.Gov/annual_reports/2010/1103_can-gender_hr.Htm accessed january 9, 2014. (more…)
Author Interviews, Ophthalmology, Stem Cells, Transplantation / 17.07.2014

Ben Mead Molecular Neuroscience Group Neurotrauma and Neurodegeneration Section School of Clinical and Experimental Medicine University of Birmingham, BirminghamMedicalResearch.com Interview with: Ben Mead Molecular Neuroscience Group Neurotrauma and Neurodegeneration Section School of Clinical and Experimental Medicine University of Birmingham, Birmingham Medical Research: What are the main findings of the study? Answer: Traumatic and neurodegenerative disease of the retina lead to an irreversible loss of retinal ganglion cells (RGC) which are the neuronal cells located in the inner retina that transmit visual signals to the brain. Thus RGC injury results in visual defects which can ultimately progress into permanent blindness. One promising therapeutic approach is the use of stem cells as a source of replacement for lost retinal cells. However a theory has emerged suggesting that stem cells can act through the secretion of signalling molecules (growth factors). One stem cell that has recently shown great promise for neuronal repair are dental pulp stem cells (DPSC), which are multipotent stem cells easily isolated from adult teeth, including third molars (Mead et al 2013, 2014). In our research, we transplanted either dental pulp stem cells or the more widely studied bone marrow-derived mesenchymal stem cell (BMSC) into the vitreous chamber of the eye after optic nerve crush (Mead et al 2013). The main finding of this study was that DPSC, to a significantly greater degree than BMSC, promoted the survival of injured RGC and the regeneration of their axons. We also showed that the mechanism of action was not through differentiation and replacement of cells but was actually paracrine mediated, i.e. through DPSC-derived growth factors (Mead et al, 2013, 2014). (more…)
Author Interviews, Kidney Disease, Transplantation / 15.07.2014

Dr Hallvard Holdaas Consultant in Nephrology National Hospital of Oslo, NorwayMedicalResearch.com Interview with: Dr Hallvard Holdaas Consultant in Nephrology Department of Transplant Medicine Oslo University Hospital Rikshospitalet, Oslo Norway. Medical Research: What are the main findings of the study? Dr. Holdaas: Most studies examining long-term risk for living kidney donors have included  comparators from the background population with hypertension, diabetes mellitus, reduced renal function, cancer and other concomitant diseases; or for the few studies with more “healthy” comparators the follow-up time have been restricted. In our study we compared living donors to a healthy non-donor population which would have qualified as donors themselves, with median follow-up of 15.1 years for the donors. The relative risk for the living donors compared to a healthy control was 11.38 for endstage renal disease (ESRD), 1.4 for cardiovascular death and 1.3 for all-cause mortality (Mjoen et al., 2014). (more…)
Author Interviews, Kidney Disease, NEJM, Transplantation / 15.07.2014

Paul Kimmel, M.D. Division of Kidney, Urologic and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health Professor Division of Renal Diseases and Hypertension The George Washington UniversityMedicalResearch.com Interview with: Paul Kimmel, M.D. Division of Kidney, Urologic and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health Professor Division of Renal Diseases and Hypertension The George Washington University Medical Research:   What are the main findings of the review? Dr. Kimmel: AKI (Acute Kidney Injury) and CKD (Chronic Kidney Disease), two syndromes approached separately in medical school  curricula  as well as in the clinical arena are inextricably intertwined.  They should be taught as a combined entity, culminating in progressive loss of renal function necessitating renal replacement therapy (dialysis or transplantation). The two syndromes increase risk for cardiovascular disease and diminished quality of life as well.  Preventive and therapeutic strategies should be directed at the combined entity. (more…)
Author Interviews, Hematology, JAMA, Stem Cells, Transplantation / 03.07.2014

John F. Tisdale, MDMedicalResearch.com Interview with: Dr. John Tisdale MD Molecular and Clinical Hematology Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland MedicalResearch: What are the main findings of the study? Dr. Tisdale: Using a nonmyeloablative allogeneic HLA-match peripheral blood stem cell transplantation strategy aimed at tolerance induction, we were able to revert the phenotype in 26 of 30 adult patients with severe sickle cell disease ranging in age from 16 to 65 years. In contrast to standard transplantation strategies which rely on high doses of chemo and/or radiotherapy after which the entire bone marrow and blood system is replaced by that of the donor, our patients had a mixture of their own and that of their donor. This procedure was well tolerated, with no non-relapse mortality, and led to complete replacement of red blood cells by that of the donor in successfully engrafted patients. This replacement resulted in decreases in pain, pain medication usage, hospitalizations, and improvements in organ function. (more…)
Author Interviews, Connective Tissue Disease, Transplantation / 03.07.2014

MedicalResearch.com Interview with: ProfProf. Dr. Jacob M. van Laar Professor and Chair Dept of Rheumatology & Clinical Immunology University Medical Center Utrecht . Dr. Jacob M. van Laar Professor and Chair Dept of Rheumatology & Clinical Immunology University Medical Center Utrecht MedicalResearch: What are the main findings of the study? Prof. van Laar: The results of the ASTIS-trial demonstrate that stem cell transplantation in selected patients with early, diffuse cutaneous systemic sclerosis, a rare, autoimmune connective tissue disease, prolongs long-term survival and improves clinical manifestations (skin, lung) and quality of life, when compared to monthly infusions with cyclophosphamide. The benefits must be weighed against the risks which include early  treatment-related mortality (10% in the ASTIS-trial) and viral infections. (more…)
Diabetes, Transplantation, Weight Research / 03.07.2014

Yalcin Basaran, MD Gulhane Military Medical Academy School of Medicine Ankara, Turkey.MedicalResearch.com Interview with: Yalcin Basaran, MD Gulhane Military Medical Academy School of Medicine Ankara, Turkey. MedicalResearch: What are the main findings of the study? Dr. Basaran: We designed a cross-sectional study to identify the relation between the gut microbiota composition and obesity and diabetes. 27 severely obese individuals (20 men and 7 women with mean BMI: 39.98±5.56 kg/m2), 26 patients with newly diagnosed type 2 diabetes (18 men and 8 women with mean BMI: 28.63±5.08 kg/m2) and 28 healthy control subjects (22 men and 6 women with mean BMI: 23.02±1.70 kg/m2), between 18-65 years of age, were included in the present study. None of the participants was undergoing chronic treatment and no antibiotics, probiotics or prebiotics were taken within 3 months before collecting fecal material. Fecal samples were self-collected in sterile boxes, stored at -80o until analysis, and analyzed by quantitative real-time PCR for the presence of the most common types of intestinal bacteria. Although tended to increase, we observed no significant difference between the three groups in regards to fecal concentrations of Bacteroidetes. There was also no considerable difference in the fecal Bifidobacteria, Firmicutes and Clostridium Leptum levels among the obesity and diabetes groups. However, Bifidobacteria, Firmicutes and Clostridium Leptum counts were all significantly lower in obese and diabetic patients compared with healthy control individuals. Additionally, logistic regression analysis showed that parameters of adiposity (weight, BMI and waist circumference) and those of glucose control (FBG and HbA1c) were related to the altered gut microbiota composition. This suggests that alterations in the gut microbiota composition may influence metabolic profile in humans. (more…)
Author Interviews, Kidney Disease, Transplantation / 01.07.2014

Daniela P Ladner, MD, MPH, FACS Assistant Professor Transplant Surgery Department of Surgery, Division of Organ Transplantation Director Northwestern University Transplant Outcomes Research Collaborative (NUTORC) Comprehensive Transplant Center Feinberg School of Medicine, Northwestern UniversityMedicalResearch.com Interview with Daniela P Ladner, MD, MPH, FACS Assistant Professor Transplant Surgery Department of Surgery, Division of Organ Transplantation Director Northwestern University Transplant Outcomes Research Collaborative (NUTORC) Comprehensive Transplant Center Feinberg School of Medicine, Northwestern University MedicalResearch: What are the main findings of the study? Dr. Ladner: With the current kidney organ allocation system, there exists significant geographic disparity between the 58 Donor Services Areas (DSAs) in the US, which are distributed among 11 regions. This means that depending on where a patient lives it might take shorter or longer to receive a kidney organ for transplantation. Despite efforts, this has not improved over the course of 20 years and in most regions this has worsened. In 1991 and 1992 respectively, two states changed their kidney allocation system, such that kidneys would first be allocated with the DSA of procurement, then statewide, then regionally (which may include several states) and then nationally. Usually kidneys don’t get allocated statewide before regionally. The main finding of this study is that in those two states (FL, TN), where a minor change to the kidney allocation was put into place, there was significant reduction in the geographic disparity between their Donor Services Areas. In other comparable states (equal numbers of DSAs within the state) the geographic disparity did not improve and in many the geographic disparity worsened. (more…)
Author Interviews, BMJ, Cancer Research, Surgical Research, Transplantation / 02.05.2014

MedicalResearch.com Interview with: Rajeev Desai SpR Gastroenterology, City Hospital Birmingham Honorary Clinical Research Fellow University Hospital Birmingham / NHS Blood and Transplant, Bristol MedicalResearch: What are the main findings of the study? Dr. Desai: This study of a large national cohort of organ donors shows that, following careful assessment and selection, organs from some donors with a previous history of cancer can be used safely for transplantation. The risks of accepting such organs for transplantation should be balanced with risks of non-acceptance and its consequences including delayed transplantation or non-transplantation. (more…)
Author Interviews, BMJ, Gastrointestinal Disease, Transplantation / 29.04.2014

Mr. Thamara Perera FRCS Consultant Surgeon - Multi Organ Retrieval and Liver Transplant Liver Transplant - University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham, UKMedicalResearch.com Interview with: Mr. Thamara Perera FRCS Consultant Surgeon - Multi Organ Retrieval and Liver Transplant Liver Transplant - University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham, UK MedicalResearch.com: What are the main findings of the study? Answer: In this study we compared the basic energy metabolism of liver grafts obtained from conventional and widely practiced form of organ donation, the donation after brain death (DBD) donors, and recently revived form of organ donation called donation after circulatory death (DCD) donors. To introduce a background to this study - DCD liver grafts are perceived as marginal liver grafts, owing to the basic differences surrounding the organ donation. DCD organs suffer a period of warm ischemia from the time of treatment withdrawal in a potential donor up until the organs are actually recovered and preservation is initiated. Although the DCD liver grafts have supplemented the donor organ pool, the initial and short-term results following liver transplantation are comparatively poor and these differences are attributable to the donor warm ischemia. However there were no studies in the literature examining the energy status of DCD liver grafts and our study is the first such study. (more…)
Annals Internal Medicine, Author Interviews, Infections, Transplantation / 01.03.2014

MedicalResearch.com Interview with: Dr. Susan N. Hocevar MD Centers for Disease Control and Prevention Atlanta, GA 30333; MedicalResearch.com:  What are the main findings of the study? Dr. Hocevar: This public health investigation uncovered microsporidiosis transmitted to 3 organ recipients who received organs from a common donor. This illness cluster was the first recognized occurrence of donor-derived microsporidiosis. (more…)
Author Interviews, Ophthalmology, Transplantation, UT Southwestern / 31.12.2013

Dr. Jerry Y. Niederkorn, Ph.D. George A. and Nancy P. Shutt Professorship in Medical Sciences Royal C. Miller Chair in Age-Related Macular Degeneration Research Professor of Ophthalmology and Microbiology Vice Chair, Research (Department of Ophthalmology) Department of Ophthalmology, University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with: Dr. Jerry Y. Niederkorn, Ph.D. George A. and Nancy P. Shutt Professorship in Medical Sciences Royal C. Miller Chair in Age-Related Macular Degeneration Research Professor of Ophthalmology and Microbiology Vice Chair, Research (Department of Ophthalmology) Department of Ophthalmology, University of Texas Southwestern Medical Center Dallas, TX FN-γ Blocks CD4+CD25+ Tregs and Abolishes Immune Privilege of Minor Histocompatibility Mismatched Corneal Allografts MedicalResearch.com: What are the main findings of the study? Dr. Niederkorn: These findings indicate that a combination of two simple maneuvers increases the acceptance of corneal transplants. In the past, there was no clear benefit in performing tissue matching of the cornea donor’s major histocompatibility complex (MHC) with the recipient of the corneal transplant. However, our study in experimental animals revealed that blocking a single immune system molecule called interferon-gamma (IFN-γ) combined with matching the corneal transplant donor with the transplant recipient’s MHC gene complex reduced the risk of rejection to less than 10% in the total absence of anti-rejection drugs. This study revealed that blocking this single immune system molecule promoted the development of immune system cells called T regulatory cells (Tregs) that suppressed the lymphocytes that are responsible for attacking organ transplants. (more…)
Author Interviews, Gastrointestinal Disease, Pediatrics, Race/Ethnic Diversity, Transplantation / 10.12.2013

Rachel Patzer, PhD, MPH Assistant Professor Emory University School of Medicine Department of Surgery, Division of TransplantationMedicalResearch.com Interview with: Rachel Patzer, PhD, MPH Assistant Professor Emory University School of Medicine Department of Surgery, Division of Transplantation MedicalResearch.com: What are the main findings of the study? Dr. Patzer: We found significant racial/ethnic differences in important health outcomes among pediatric and adolescent patients who received a liver transplantation at a large transplant center in the Southeastern U.S., where rates of mortality and graft failure were higher among minorities compared to white patients. (more…)
Annals Thoracic Surgery, Author Interviews, Heart Disease, Transplantation, Vanderbilt / 12.08.2013

Simon Maltais MD PhD Vanderbilt University Medical Center Division of Cardiovascular Surgery 1215 21st Ave S, MCE 5th Flr Nashville, TN 37232-8808.MedicalResearch.com Interview with: Simon Maltais MD PhD Vanderbilt University Medical Center Division of Cardiovascular Surgery 1215 21st Ave S, MCE 5th Flr Nashville, TN 37232-8808. MedicalResearch.com: What did your study evaluate and why is this important? Answer: We performed a rigorous, retrospective review of the Scientific Registry of Transplant Recipients (SRTR) data base to evaluate donor, recipient, and technical characteristics associated with graft survival in patients undergoing mechanical circulatory support (MCS) device explantation at the time of heart transplantation surgery. Donor and recipient characteristics has been well described in the medical literature for routine heart transplantation, however these characteristics in patients who were supported with a long term MCS device at the time of heart transplant was not known.  Additionally, due to chronic donor heart shortages, an increasing number of patients with advanced heart failure are being bridged with MSC devices until a suitable donor heart can be obtained. (more…)