Author Interviews, Leukemia, NEJM, Transplantation / 08.09.2016

MedicalResearch.com Interview with: [caption id="attachment_27654" align="alignleft" width="133"]Dr. Filippo Milano, MD, PhD Assistant Member, Clinical Research Division Associate Director Cord Blood Transplantation Cord Blood Program Assistant Professor, University of Washington Fred Hutchinson Cancer Research Center Dr. Filippo Milano[/caption] Dr. Filippo Milano, MD, PhD Assistant Member, Clinical Research Division Associate Director Cord Blood Transplantation Cord Blood Program Assistant Professor, University of Washington Fred Hutchinson Cancer Research Center MedicalResearch.com: What is the background for this study? Response: When first introduced, cord blood (CB) graft was used only as a last resort when no suitable conventional donor could be identified, largely due to the limiting cell doses available in a cord blood graft. A CB graft, however, is attractive due to the increased level of HLA disparity that can be tolerated, without increased risk of graft versus host disease, allowing nearly all patients to find such a donor. The main intent of the study was to evaluate whether or not, at our Institution, cord blood SHOULD STILL BE considered only AS an alternative DONOR or IF instead outcomes were comparable to those obtained with more “conventional” types of transplants from matched and mismatched unrelated donors.
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JACC, Transplantation / 30.08.2016

MedicalResearch.com Interview with: [caption id="attachment_27286" align="alignleft" width="125"]Dr. Laith Alshawabkeh MD ‎Senior Fellow Brigham & Women's and Boston Childrens Hospitals / Harvard Medical School Dr. Laith Alshawabkeh[/caption] Dr. Laith Alshawabkeh MD ‎Senior Fellow Brigham & Women's and Boston Childrens Hospitals / Harvard Medical School MedicalResearch.com: What is the background for this study? Response: As the number of adults living with congenital heart disease continues to increase, there is paucity of evidence on the trajectories and patterns of their comorbidities. In all, heart failure is the leading cause of death in this group of patients. Unfortunately, landmark trials and advances in medical therapy which promoted increase survival in patients with the usual heart failure (non-congenital) has not been translated into those with congenital heart disease. Heart transplantation remains one of the (if not the only) sustainable option for many patients with congenital heart disease at the end stage of heart failure. Recent studies have shown that adults with congenital heart disease who underwent transplantation experienced higher risk of postoperative mortality compared to their non-congenital counterparts; however, patients with congenital heart disease who survived the first year post-transplantation enjoyed significantly better long-term survival, indicating that with careful selection those patients might benefit tremendously from transplantation. Much less is known about the outcome of these patients while they are waiting for an organ. As such, this study sought to examine the outcomes of patients with congenital heart disease while listed for heart transplantation and to investigate correlates of adverse outcomes (mortality and delisting due to clinical worsening).
Author Interviews, Transplantation / 16.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26937" align="alignleft" width="142"]Guo-fu Hu, PhD Investigator in the Molecular Oncology Research Institute Tufts Medical Center Dr. Guo-fu Hu[/caption] Guo-fu Hu, PhD Investigator in the Molecular Oncology Research Institute Tufts Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Angiogenin (ANG) is a ribonuclease that is known to promote cell growth and survival by differential processing of cellular RNAs. This paper reports three main findings.
  • 1) ANG has a cell type-specific role in regulating cell proliferation of the hematopoietic system: it promotes quiescence of the primitive hematopoietic stem/progenitor (HSPC) cells while simultaneously stimulating proliferation of more differentiated myeloid progenitor (MyePro) cells.
  • 2) ANG regulatesquiescence and proliferation of HSPC and MyePro through a novel mechanism: it induces tRNA-derived stress-induced small RNA (tiRNA) generation in HSPC and ribosomal RNA (rRNA) induction in MyePro, leading to respective reduction and increase in protein synthesis. To our knowledge, this is the first report of cell type specificity in RNA processing that leads to or originates from a different cellular state.
  • 3) Recombinant ANG protein is able to improve survival of irradiated animals and enhances hematopoietic regeneration of mouse and human HSPC in transplantation, which have significant implication in a number of clinical situations including bone marrow failure and stem cell transplantations.
Author Interviews, Immunotherapy, Leukemia, Stem Cells, Transplantation / 12.08.2016

MedicalResearch.com Interview with: [caption id="attachment_26960" align="alignleft" width="200"]Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016 Felix Garzon[/caption] Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016 MedicalResearch.com: What is the background for this study? What is goal of this Study? Response: Iomab-B (“Iomab”) was developed at the Fred Hutchinson Cancer Research Center (“the Hutch”) in Seattle, Washington. The Hutch is a pioneer in the field of bone marrow transplantation (BMT) having 3 Nobel Prizes and doctors there performed some of the first transplants for leukemia patients. Iomab-B is intended to be an induction and conditioning agent prior to a BMT for patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are over the age of 55. BMT is the only potentially curative option for AML i.e. for this patient population that currently has a survival prognosis of 2-6 months which means that if Iomab-B is successful it would create a new market segment and offer patients a great clinical benefit and a hope for a cure. Actinium Pharmaceuticals licensed Iomab from the Hutch in 2012 and prior to us licensing Iomab, it had been studied in almost 300 patients in several phase 1 and phase 2 clinical trials in an array of blood cancers, both leukemias and lymphomas. Actinium is now the sponsor of a pivotal phase 3 trial for Iomab-B to study its use as an induction and conditioning agent prior to a bone marrow transplantation in patients with relapsed or refractory AML who are over the age of 55. This trial, which we have named the SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial, started at the end of June 2016 and we expect to enroll 150 patients by the end of 2017. The primary endpoint of the SIERRA trial is durable complete remissions (dCR) of 6 months. The study arm will consist of Iomab-B administration followed by a  bone marrow transplantation, patients will be evaluated for dCR at 6 months after engraftment, which will be assessed at day 28 or day 56. The control arm of the study will be physician’s choice of chemotherapy and if the patient is able to achieve a complete remission (CR) they may receive a BMT or some other form of treatment with curative intent. The study is designed to evaluate if the study arm of Iomab-B and a BMT can double the dCR rate of the control arm, which is designed to replicate the current treatment regimen prior to a bone marrow transplantation .
Author Interviews, Microbiome, Transplantation / 23.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25456" align="alignleft" width="150"]Maria-Luisa Alegre, MD, PhD Professor of medicine University of Chicago Dr. Maria Luisa Alegre[/caption] Maria-Luisa Alegre, MD, PhD Professor of medicine University of Chicago MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most of the research that investigates why/how transplanted organs are rejected has focused on the genetic disparities between the donor and the recipient. Foreign proteins in the donor organ are recognized by the immune system of the host, which becomes activated to reject the transplanted organ. This is why transplant recipients need to take immunosuppressive medications for the rest of their lives. Whether environmental factors, in addition to genetic factors, can also affect how the immune system is activated by the transplanted organ is much less understood. In particular, the microbiota, the communities of microbes that live on and in our body, is distinct in each individual and is known to affect the function of the immune system in diseases ranging from autoimmunity to cancer. Using mouse models of skin and heart transplantation, we investigated if the microbiota was an environmental factor that could affect the speed at which the immune system rejects a transplanted organ. We found that the microbial communities that colonize the donor and the host fine-tune the function of the immune system and control the strength with which the immune system reacts to a transplanted organ.
Author Interviews, Hematology, HIV, Stem Cells, Transplantation / 15.06.2016

MedicalResearch.com Interview with: [caption id="attachment_25218" align="alignleft" width="120"]Joseph Alvarnas, MD Associate clinical professor Department of hematology and Director of value-based analytics City of Hope National Medical Center Duarte, CA Dr. Joseph Alvarnas[/caption] Joseph Alvarnas, MD Associate clinical professor Department of hematology and Director of value-based analytics City of Hope National Medical Center Duarte, CA MedicalResearch.com: What is the background for this study? Dr. Alvarnas: Patients with HIV infection have a significantly increased risk of non-Hodgkin lymphoma and Hodgkin lymphoma. Prior to the availability of effective anti-retroviral therapy, HIV-infected patients with lymphoma had very poor treatment outcomes. Following the availability of effective anti-HIV therapy, patient outcomes for HIV-infected patients now parallel those of non-infected patients. Historically, however, HIV infection has been used as a criterion for not offering patients autologous blood stem cell transplantation outside of centers with unique expertise. The purpose of this trial was to evaluate outcomes, complication rates, and immunological reconstitution of HIV-infected patients following autologous blood stem cell transplantation.
Author Interviews, Gastrointestinal Disease, Microbiome, Transplantation / 16.05.2016

MedicalResearch.com Interview with: Dr. Sudarshan Paramsothy University of New South Wales Australia MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Paramsothy: This study was conducted as there is strong evidence that the gastrointestinal microbiota play a critical role in the underlying pathogenesis of inflammatory bowel disease (IBD), but treatments to date primarily are focused on controlling the associated immune response. Attempts at therapeutic microbial manipulation in ulcerative colitis (UC) to date (antibiotics, probiotics, prebiotics) have not been as impressive as one might expect. We felt intensive fecal microbiota transplantation (FMT) may be more successful than these other methods, as it involves transplanting the entire gastrointestinal microbiota from a health individual, and thus more likely to correct any underlying microbial disturbance or dysbiosis in the recipient UC patient. Our study found that significantly more active ulcerative colitis patients treated with intensive FMT than placebo (27% vs 8%) achieved the trial primary composite endpoint of both
  • clinical remission induction (ie resolution of symptoms) and
  • endoscopic remission or response (ie either healing or significant improvement of the bowel lining)
Author Interviews, Heart Disease, Transplantation / 12.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24272" align="alignleft" width="200"]Jaimin Trivedi, MD, MPH Instructor Department of Cardiovascular and Thoracic Surgery University of Louisville Louisville, KY 40202 Dr. Jaimin Trivedi[/caption] Jaimin Trivedi, MD, MPH Instructor Department of Cardiovascular and Thoracic Surgery University of Louisville Louisville, KY 40202 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Trivedi: There is a donor heart shortage in United States and certain donor hearts are likely to be turned down because the donors required cardiopulmonary resuscitation (CPR) prior to procurement. The rationale behind conducting the study was to identify impact of donor CPR and its duration on recipient survival after transplantation. Our findings show that presence of CPR and duration of CPR does not adversely impact the post heart transplant survival. The study also shows that ejection fraction and peak cardiac troponins between the CPR and non-CPR donors were comparable at time of transplant suggesting recovery of cardiac function.
Author Interviews, Gender Differences, Kidney Disease, Transplantation, University of Pennsylvania / 22.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23696" align="alignleft" width="180"]Matthew Levine, MD, PhD Associate professor of Transplant Surgery Perelman School of Medicine University of Pennsylvania Dr. Mathew Levine[/caption] Matthew Levine, MD, PhD Assistant Professor of Transplant Surgery Perelman School of Medicine University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Levine: This work stemmed from a known finding that female mice tolerate kidney injury better than males and this is true of mice that share exactly the same genes.  Therefore, the gender difference was the driving factor.  My basic science laboratory works at the intersection between scientific discovery and clinical application and this led us to question whether the same phenomenon was true in humans and whether we could identify a way in which this could be used to improve injury tolerance above what is seen in untreated subjects.  What we found was that the hormonal environment seems to impact ischemia tolerance, with female environment being protective and the male environment worsening injury tolerance in ischemia models where blood flow is interrupted and then restored.  The kidneys seemed to adapt to take on the injury response of the host after transplantation, indicating that the differences were not forged into the kidney itself and therefore could be altered.  We then found that estrogen therapy improved kidney injury tolerance when given to female mice in advance of injury, but no effect was seen in male mice.  And most importantly, we found that in a large cohort of transplant recipients that female recipients had better injury tolerance after transplant than male recipients, as shown by ability to avoid dialysis in the first week after transplant, otherwise known as delayed graft function (DGF). This is a fairly major finding since it has not been observed in the literature despite several decades of transplant data being carefully studied.
Author Interviews, HPV, Kidney Disease, Transplantation, Vaccine Studies / 15.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23501" align="alignleft" width="135"]Dr. Delphine Robotham MD Division of Pediatric Nephrology Johns Hopkins University School of Medicine Baltimore, Maryland Dr. Robotham[/caption] Dr. Delphine Robotham MD Division of Pediatric Nephrology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Response: Cervical cancer is the second most common cancer in women worldwide and is almost entirely caused by high risk HPV genotypes.  Vaccines to high risk HPV genotypes have shown great success in protecting healthy women from the sequelae of infection, including cervical cancer and genital warts. Young women with a kidney transplant as well as those with chronic kidney disease have abnormal immune systems and as a result have a significantly increased burden of HPV-related disease making the potential health benefits of the HPV vaccine substantial in this particularly vulnerable population.  This study examined the immune response to the HPV vaccine among girls and young women with kidney disease. The goal of this research was to determine if girls and young women with chronic kidney disease (abnormal kidney function, on dialysis, or post kidney transplant) showed evidence of immune response to the quadrivalent HPV vaccine.  Immune response was determined by measuring the amount of antibody made by the patients against each of the 4 HPV genotypes included in the vaccine.  There are established thresholds of antibody above which patients are believed to have protection from infection.  We found that study participants with chronic kidney disease and those on dialysis had antibody levels above the threshold, indicating the vaccine should be effective in protecting them from HPV related disease.  A significant proportion of patients with kidney transplants showed evidence of inadequate antibody response.  This is important information as it means patients with a kidney transplant, whom we know are at increased risk of developing cervical cancer from HPV infection, may not be protected from HPV infections from the HPV genotypes included in the vaccine.
Author Interviews, Nature, Transplantation / 07.04.2016

MedicalResearch.com Interview with: Muhammad M. Mohiuddin, MD Cardiothoracic Surgery Research Program National Heart, Lung, and Blood Institute MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Mohiuddin: There are around 150,000 patients waiting for organ transplants. Unfortunately, the supply of human donor organs will never be able to meet this demand. We are trying to explore if animal (pig) organs can be used for these patients. Pig organs are rejected within a few minutes by humans or baboons. Therefore, we along with our industrial partner Revivicor Inc. have modified the pig genetics to knock out molecules harmful to humans and have also expressed some human genes in these pigs. Through these modifications, along with the use of novel target-specific immunosuppressive drugs, we have extended pig heart survival in the abdomen for almost 3 years. In this experimental model, the heart is transplanted in the abdomen while the original heart stays in the chest cavity. The major advantage of this model is that the baboon is kept alive, despite the rejection of the transplanted organ in the abdomen.
Author Interviews, Johns Hopkins, Kidney Disease, Race/Ethnic Diversity, Transplantation / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22072" align="alignleft" width="140"]Tanjala S. Purnell, PhD MPH Assistant Professor, Transplant Surgery and Epidemiology Johns Hopkins University School of Medicine Dr. Tanjala Purnell[/caption] Tanjala S. Purnell, PhD MPH Assistant Professor, Transplant Surgery and Epidemiology Johns Hopkins University School of Medicine  Medical Research: What is the background for this study? Dr. Purnell:  Kidney transplantation (KT) is the best treatment for most patients with end stage renal disease (ESRD), offering longer life expectancy and improved quality of life than dialysis treatment. Despite these benefits, previous reports suggest that black KT recipients experience poorer outcomes, such as higher kidney rejection and patient death, than white KT recipients. Our team wanted to examine whether this disparity has improved in recent decades. We hypothesized that advances in immunosuppression and post- kidney transplantation  management might differentially benefit black KT recipients, who were disproportionately burdened by immunological barriers, and contribute to reduced racial disparities in kidney transplantation outcomes. Medical Research: What are the main findings? Dr. Purnell: 
  1. From 1990 to 2012, 5-year failure rates of the transplanted kidney after Deceased Donor Kidney Transplantation (DDKT) decreased from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year failure after Living Donor Kidney Transplantation (LDKT) decreased from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites.
  2. Among DDKT recipients in the earliest group of patients, blacks were 39% more likely than whites to experience 5-year failure, but this disparity narrowed to 10% in the most recent group.
  3. Among LDKT recipients in the earliest group, blacks were 53% more likely than whites to experience 5-year failure, but this disparity narrowed to 37% in the most recent group.
  4. There were no statistically significant differences in 1-year or 3-year failure rates of transplanted kidneys after LDKT or DDKT in the most recent groups.
Author Interviews, Orthopedics, Transplantation / 25.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22054" align="alignleft" width="87"]Dr. Brett Crist MD FACS Associate Professor of Orthopaedic Surgery Co-Chief, Orthopaedic Trauma Division Associate Director, Joint Preservation Surgery Director, Trauma Orthopaedic Fellowship School of Medicine University of Missouri Health Dr. Brett Crist[/caption] Dr. Brett Crist MD FACS Associate Professor of Orthopaedic Surgery Co-Chief, Orthopaedic Trauma Division Associate Director, Joint Preservation Surgery Director, Trauma Orthopaedic Fellowship School of Medicine University of Missouri Health  Medical Research: What is the background for this study? What are the main findings? Dr. Crist: Some young patients have bone and/or cartilage problems on the femoral head due to disease or injury.  Resurfacing the femoral head with donated bone and cartilage tissue is often a better option for these young patients with active lifestyles, who would otherwise require an artificial joint that would limit their activities and eventually wear out. However, there is no standard method for implantation. Our study provides initial clinical evidence that larger, size-matched grafts have the potential to improve outcomes when resurfacing cartilage defects of the femoral head in the hip joint.
Author Interviews, Cancer Research, Dermatology, Transplantation / 09.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21418" align="alignleft" width="180"]Claire M. Vajdic, PhD Center for Big Data Research in Health University of New South Wales Australian Graduate School of Management Bldg, Sydney Australia. Dr. Claire Vajdic[/caption] Claire M. Vajdic, PhD Center for Big Data Research in Health University of New South Wales Australian Graduate School of Management Bldg, Sydney Australia on behalf of the authors. Medical Research: What is the background for this study? Dr. Vajdic: Lip cancer is one of the most common cancers in solid organ transplant recipients. Iatrogenic immunosuppression is a strong risk factor for lip cancer but the dose-related association between individual immunosuppressive agents and risk of lip cancer has not been examined. Therefore, we investigated the association between the type, dose and duration of immunosuppressive therapy and lip cancer risk in Australian liver, heart and lung transplant recipients.
Author Interviews, Immunotherapy, NEJM, Transplantation, UCSF / 29.01.2016

MedicalResearch.com Interview with: [caption id="attachment_21074" align="alignleft" width="144"]Dr. Flavio Vincenti Dr. Flavio Vincenti[/caption] Dr. Flavio Vincenti, M.D Clinical Professor of Medicine and Surgery Departments of Medicine and Surgery Endowed Chair in Kidney Transplantation University of California, San Francisco San Francisco, CA 94143 Medical Research: What is the background for this study? What are the main findings? Dr. Vincenti: This is a phase 3 study of belacept immunosuppression as compared to cyclosporine based immunosuppression in renal transplant recipients randomly assigned to 2 treatments arms of belatacept and a controlled arm consisting of cyclosporine. The main finding of this study is that Belatacept, a fusion receptor protein that blocks co-stimulation and is administered intravenously on the maintenance of a 4 weekly maintenance therapy, had superior outcomes at 5 and 7 years as compared to patients on a CsA-based regimen. The 7 year data show that patients on either arm of belatacept had a 43 percent risk reduction of deaths or grafts loss as compared to patients treated with cyclosporine. In addition, belatcept patients had significantly better preservation of renal function throughout the 7 years of follow up and had lower incidence of donor specific antibodies. Nephrotoxicity from cyclosporine and donor specific antibodies are important causes of late graft loss.
Author Interviews, Brigham & Women's - Harvard, Dermatology, JAMA, Melanoma, Transplantation / 20.01.2016

More on Dermatology from MedicalResearch.com  [caption id="attachment_20781" align="alignleft" width="115"]Pritesh S. Karia, MPH Manager-Dermatologic Oncology Research Program Mohs and Dermatologic Surgery Center Brigham and Women's Hospital Boston, MA 02130 Pritesh Karia[/caption] MedicalResearch.com Interview with: Pritesh S. Karia, MPH Manager-Dermatologic Oncology Research Program Mohs and Dermatologic Surgery Center Brigham and Women's Hospital Boston, MA 02130  Medical Research: What is the background for this study? Response: Several recent studies have shown a reduced incidence of skin cancer in organ transplant recipients (OTR) treated with sirolimus as first-time therapy and those converted from calcineurin inhibitors to sirolimus. Although cancer formation is one of the main reasons for conversion to sirolimus, studies examining the effect of sirolimus on the risk of subsequent cancer formation in organ transplant recipients who have already been diagnosed with a post-transplant cancer are limited.
Author Interviews, Cancer Research, JAMA, Transplantation / 11.01.2016

[caption id="attachment_20526" align="alignleft" width="180"]Sergio A. Acuna, MD Graduate Student at St. Michael's Hospital and IHPME University of Toronto Dr.  Sergio Acuna[/caption] MedicalResearch.com Interview with: Sergio A. Acuna, MD Graduate Student at St. Michael's Hospital and IHPME University of Toronto Medical Research: What is the background for this study? Dr. Acuna: Solid organ transplant recipients are known to be at greater risk of developing cancers compared to the general population; however, because they are also at high increased risk of mortality from non-cancer causes, the risk of cancer morality in this population is unclear. As previous studies on this topic have reported disparate findings, the cancer mortality risk in this population remained uncertain. Medical Research: What are the main findings? Dr. Acuna: Our study provides conclusive evidence that solid organ transplant recipients are at increased risk of cancer mortality. Our findings demonstrate that solid organ transplant recipients are at increased risk of cancer death compared to the general population regardless of age, transplanted organ, and year of transplantation, and indicate cancer is a substantial cause of death in this population.
Author Interviews, Frailty, Mayo Clinic, Pulmonary Disease, Transplantation / 23.12.2015

[caption id="attachment_20197" align="alignleft" width="125"]Cassie Kennedy, M.D. Pulmonology and Critical Care Medicine Mayo Clinic Dr. Cassie Kennedy[/caption] MedicalResearch.com Interview with: Cassie Kennedy, M.D. Pulmonology and Critical Care Medicine Mayo Clinic  Medical Research: What is the background for this study? Dr. Kennedy: Lung transplant is a surgical procedure that can offer extended life expectancy and improved quality of life to selected patients with end-stage lung disease. However there are about 1700 patients awaiting lung transplant at any given time in the United States because transplant recipients far exceed potential donors.  In addition, even with carefully chosen candidates, lung transplant recipients live on average about 5.5 years.  It is therefore very important for transplant physicians to choose patients who will receive the most benefit from their lung transplant. Frailty (defined as an increased vulnerability to adverse health outcomes) has typically been a subjective consideration by transplant physicians when choosing lung transplant candidates.  The emergence of more objective and reproducible frailty measures from the geriatric literature present an opportunity to study the prevalence of frailty in lung transplant (despite that subjective screening) and to determine whether the presence of frailty has any impact on patient outcomes. Medical Research: What are the main findings? Dr. Kennedy: Frailty is quite common --46 percent of our patient cohort was frail by the Frailty Deficit Index. We also saw a significant association between frailty and worsened survival following lung transplantation: one-year survival rate for frail patients was 71.7 percent, compared to 92.9 percent for patients who were not frail. At three years this difference in survival persisted--the survival rate for frail patients was 41.3 percent, compared to 66.1 percent for patients who were not frail.
Author Interviews, Cancer Research, Prostate Cancer, Surgical Research, Transplantation / 23.12.2015

[caption id="attachment_20256" align="alignleft" width="150"]Gerardo Vitiello Dr. Vitiello[/caption] MedicalResearch.com Interview with: Gerardo Vitiello, MD Emory University School of Medicine Emory Transplant Center NYU Langone Medical Center Department of Surgery  Medical Research: What is the background for this study? What are the main findings? Dr. Vitiello:   Screening for prostate cancer with prostate specific antigen (PSA) levels is highly controversial, as it is a non-specific marker for prostate cancer. A PSA level may be elevated in a variety of disease processes (not only prostate cancer), and even in the general population, the benefit of early intervention for prostate cancer is unclear. In contrast, end stage renal disease (ESRD), where patients no longer have renal function and require dialysis, is a major health problem with a huge impact on a patient’s quality of life. The only cure for ESRD is kidney transplantation, which has been shown to have an enormous health and quality of life benefit for transplant recipients. Transplant centers have rigorously screened candidates for potential malignancy prior to transplantation to ensure that there are no contraindications to receiving a transplant. For the first time, we demonstrate that screening for prostate cancer in kidney transplant candidates is not beneficial, and may actually be harmful, since it delays time to transplant and reduces a patient’s chance of receiving a transplant without an apparent benefit on patient survival.
Author Interviews, Endocrinology, Kidney Disease, Transplantation, Vitamin K / 21.12.2015

MedicalResearch.com Interview with: Josep M Cruzado, MD Head, Nephrology Department Hospital Universitari de Bellvitge  Medical Research: What is the background for this study? What are the main findings? Dr. Cruzado: Tertiary hyperparathyroidism is frequent after renal transplantation. Inappropriately high parathyroid hormone levels are associated with hypercalcemia, hyperphosphatemia, both allograft and vascular calcification and bone mineral density loss. Cinacalcet is highly effective to control hypercalcemia in this setting although there were no studies comparing cinacalcet with subtotal parathyroidectomy. Main findings are that subtotal parathyroidectomy is superior to cinacalcet in normalizing hypercalcemia amb iPTH, increased bone mineral density at femoral neck and is more cost effective (the cost of subtotal parathyroidectomy is equal to 14 months of cinacalcet and this drug should be maintained overtime).
Author Interviews, Hepatitis - Liver Disease, Surgical Research, Transplantation, Weight Research / 17.11.2015

[caption id="attachment_19426" align="alignleft" width="97"]Barry Schlansky, M.D., M.P.H Assistant Professor of Medicine Oregon Health & Science University Dr. Schlansky[/caption] MedicalResearch.com Interview with: Barry Schlansky, M.D., M.P.H Assistant Professor of Medicine Oregon Health & Science University Medical Research: What are the main findings and significance of this study? Dr. Schlansky: This study examines how obese patients fare before and after liver transplantation. Similar to other researchers, we found that obese patients do just as well as normal weight patients after liver transplantation. We were surprised, however, to find that very obese patients died more often while on the wait list before liver transplant.
Author Interviews, NYU, Surgical Research, Transplantation / 16.11.2015

Patrick Hardison was severely injured in September 2001 in Mississippi, while attempting to rescue a woman in a burning home. He had dozens of surgeries as he continued to try to work and care for his five children. These surgeries grafted skin from his legs onto his entire scalp and face. [caption id="attachment_19420" align="alignleft" width="300"]Patrick Hardison before surgery (left) and in November 2015, nearly three months after the surgery Patrick Hardison before surgery (left) and in November 2015, nearly three months after the surgery.[/caption] Mr. Hardison was referred to Dr. Eduardo D. Rodriguez, of NYU Langone Medical Center for consideration of facial transplantation. Three months August 14, 2015 ago Dr. Rodriguez were able to give Patrick a new face, scalp, ears and ear canals, new eyelids and the muscles that control blinking.  
Author Interviews, Columbia, Heart Disease, JACC, Transplantation / 14.11.2015

[caption id="attachment_19394" align="alignleft" width="149"]Raymond Givens MD PhD Columbia University Medical Center Dr. Givens
(photo Seth Wenig)[/caption] MedicalResearch.com Interview with: Raymond Givens MD PhD  Columbia University Medical Center  Medical Research: What is the background for this study? What are the main findings? Dr. Givens: Multiple listing- i.e., simultaneous placement on multiple organ transplant waiting lists- is allowed by the United Network for Organ Sharing (UNOS). Because insurance generally does not pay for the costs of transportation between multiple centers or of temporary housing, there has been concern that the multiple-listing policy gives an unfair advantage to wealthier patients. We examined the UNOS database from 2000-2013 and identified 33,928 patients who were listed for a first-time single-organ heart transplant, 2% of whom met our definition of multiple-listing. Compared to single-listed patients, multiple-listed patients lived in ZIP codes with significantly higher median incomes, and were more likely to have private insurance and less likely to be supported by Medicaid. They were also significantly more likely to have blood type O and to live in areas with higher predicted waiting times. Despite having lower listing priority at the start of the primary listing and lower predicted mortality, the multiple-listed patients were often upgraded at secondary listing and had a higher eventual transplant rate (74.4% vs 70.2%) and lower mortality rate while listed (8.1% vs 12.2%). When the multiple-listed cohort was compared against a propensity-score-matched single-listed subset the relative rare of transplant was 3.02. There were no differences in post-transplant survival.
Author Interviews, Kidney Disease, Transplantation / 10.11.2015

MedicalResearch.com Interview with: Sumit Mohan, MD, MPH Assistant Professor of Medicine & Epidemiology Director, Transplant Outcomes Research at CUMC Division of Nephrology, Department of Medicine Columbia University Medical Center   Medical Research: What is the background for this study? What are the main findings? Dr. Mohan: Kidney transplantation is the preferred treatment for End Stage Renal Disease but transplantation access is limited in part to the scarcity of organs in the United States. Despite this, currently 17% of all kidneys that are procured in the United States for transplant are discarded - a number that has been steadily increasing. The reasons for the discard of these kidneys is poorly understood and urgently needs to be studied.
Author Interviews, C. difficile, Gastrointestinal Disease, Transplantation / 22.10.2015

[caption id="attachment_18592" align="alignleft" width="214"]Monika Fischer, MD, MSCR Assistant Professor of Clinical Medicine Division of Gastroenterology and Hepatology Indiana University Indianapolis, IN 46202 Dr. Monika Fischer[/caption] MedicalResearch.com Interview with: Monika Fischer, MD, MSCR Assistant Professor of Clinical Medicine Division of Gastroenterology and Hepatology Indiana University Indianapolis, IN 46202  Medical Research: What is the background for this study? What are the main findings? Dr. Fischer: Cumulative evidence based upon case series and randomized trials suggest high success rate with 10-20 % failing a single FMT (fecal microbiota transplant). Predictors of failures are not known. In a collaborative study between Indiana and Brown Universities we aimed to identify clinical predictors of FMT failure. Results were the following:
  • N= 345 patients
    • Brown: N=166
    • IU: N=179
  • Average age: 62 years
  • Females: 72%
  • IBD: 18%
  • Immunosuppression: 24%
  • Indication for FMT
    • Recurrent CDI: 74%
    • Refractory CDI: 26%
    • Severe/complicated CDI: 13%
  • Inpatient FMT: 17%
  • Patient directed donor: 40%
Overall failure rate was 23.7%. Broken down by fecal microbiota transplant indication, while only 18% of patients failed and  needed further therapy in the non-severe category, 1 in 2 (50%) severe C. difficile infection (CDI) patients failed a single fecal microbiota transplant and needed further therapy for cure.
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015

[caption id="attachment_18565" align="alignleft" width="125"]Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Dr. Sahil Khanna[/caption] MedicalResearch.com Interview with: Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83..
Author Interviews, Cleveland Clinic, Heart Disease, JACC, Kidney Disease, Transplantation / 13.10.2015

W.H. Wilson Tang, MD, FACC Assistant Professor in Medicine, Cleveland Clinic Lerner College of Medicine Staff, Section of Heart Failure & Cardiac Transplant Medicine Assistant Program Director, General Clinical Research Center (GCRC) The Cleveland Clinic Cleveland, OHMedicalResearch.com Interview with: W.H. Wilson Tang, MD, FACC  Assistant Professor in Medicine, Cleveland Clinic Lerner College of Medicine Staff, Section of Heart Failure & Cardiac Transplant Medicine Assistant Program Director, General Clinical Research Center The Cleveland Clinic  Cleveland, OH Medical Research: What is the background for this study? What are the main findings? Dr. Tang: Cardiac function is a key determinant of outcomes after surgery, especially transplantation. End-stage renal disease (ESRD) poses a unique scenario, as the metabolic and uremic derangements that result from this condition lead to adverse cardiac remodeling, and kidney transplantation offers a potential for reverse remodeling. We studied patients who underwent kidney transplantation and found that echocardiogram following transplantation demonstrated consistent and significant improvement in cardiac structure and function. Post-transplant improvement in anemia was a vital factor that independently predicted such positive changes, whereas post-transplant changes in blood pressure, renal function at 12 months, and dialysis duration duration did not. Moreover, patients that demonstrated reverse remodeling had outcomes comparable to those with normal baseline cardiac function.
Author Interviews, Personalized Medicine, Transplantation, University of Pennsylvania / 05.10.2015

MedicalResearch.com Interview with: Brendan J. Keating, DPhil Assistant professor of Transplant Surgery Penn Medicine Medical Research: What is the background for this study? What are the main findings? Response: Genetic studies in transplantation have been plagued by small samples and very complex phenotypes/outcomes of patients. Transplanted individuals are typically on potent immunosuppression drugs for the rest of their lives, as they have 3.5 million to 10 million variants difference from an unrelated transplanted donor organ. Such populations would certainly benefit from large well-powered genetic studies but only 3 transplant genome-wide genotyping studies comprising a few hundred individuals have been published. The papers outline the resources in hand for the International Genetics & Translational Research in Transplantation Network, comprising 22 studies to date (since the publication it has now expanded to 25 studies and > 32,000 subjects with genome-wide genotyping data). We show significant statistical power in iGeneTRAiN to detect main effect association signals across regions such as the MHC region (which harbors the HLA Class I/II regions which are well established to associate with transplantation outcomes). We also show strong genome-wide power to detect transplant outcomes that span all solid organs including graft survival, acute rejection, new onset of diabetes after transplantation (fast becoming the most common comorbidity post-transplantation), and delayed graft function (to date we have looked at this in kidney transplant patients only). We show that iGeneTRAiN is statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The transplant specific GWAS array that we designed (described in depth in the Genome Medicine paper) show that the coverage in key transplant associated regions is much higher than conventional arrays, and we describe the ‘imputation’ pipeline to expand the 780,000 or so variants examined in any given individual to > 15 millions of variants using whole genome sequencing reference datasets.
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.
Author Interviews, Brigham & Women's - Harvard, JAMA, Transplantation / 03.06.2015

Paula Chatterjee, MD, MPH Department of Medicine, Brigham and Women’s Hospital Harvard Medical School Boston, MassachusettsMedicalResearch.com Interview with: Paula Chatterjee, MD, MPH Department of Medicine, Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Chatterjee: Thousands of patients die every year due to organ shortages. Finding ways to address this public health issue is critical. States have designed a variety of strategies to promote organ donation and transplantation, however we don’t know if any of these strategies have been successful. The goal of our study was to try to figure out which strategies have been most successful in terms of increasing organ donation and transplantation. We found that states have implemented a wide and creative set of strategies, but unfortunately, it seems that these strategies have had almost no effect on increasing organ donation and transplantation. In states that adopted these strategies compared to those that did not, the rates of donation and transplantation increased at nearly the same rate over the past two decades. The only strategy that seemed to have a small effect was when states created revenue pools dedicated toward organ donation activities.