Letermovir (Prevymis) Prevents CMV Infection in Stem Cell Transplant

MedicalResearch.com Interview with:

Francisco M. Marty, M.D Associate Professor, Harvard Medical School Dana–Farber Cancer Institute and Brigham and Women’s Hospital

Dr. Marty

Francisco M. Marty, M.D
Associate Professor, Harvard Medical School
Dana–Farber Cancer Institute and
Brigham and Women’s Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cytomegalovirus (CMV) is the most common infection in patients who undergo allogeneic hematopoietic-cell transplantation (bone marrow transplantation with cells from donors different than the patient). Up until now, we had no antiviral agent that could be used for prophylaxis (prevention) of CMV post-transplant because of the side effects of drugs available to date (ganciclovir, valganciclovir, foscarnet, cidofovir).

This trial confirmed that letermovir was highly effective in preventing CMV infection when used in the first 100 days after allogeneic HCT, was associated with minimal side effects of concern and was also associated with lower all-cause mortality by Week 24 post-HCT.

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CMV Infections Increase Complications and Costs After Stem Cell Transplantation

MedicalResearch.com Interview with:

Dr. Jonathan Schelfhout, PhD Director, Outcomes Research Merck & Co. Inc. North Wales, PA

Dr. Schelfhout

Dr. Jonathan Schelfhout, PhD
Director, Outcomes Research
Merck & Co. Inc.
North Wales, PA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The cost of hematopoietic stem cell transplantation has received increased attention after it was identified as a top 10 contributor to increasing healthcare costs in an AHRQ 2016 report. Many recent studies have explored the cost of HSCT but additional research is needed on the costly complications that can follow the transplant procedure. This research is particularly relevant for inpatient decision makers, as most transplant centers receive one bundled payment for the transplant and the treatment of any complications over the first 100 days.

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Deceased Donor Kidneys Offered Median of 7 Times Before Acceptance For Transplant

MedicalResearch.com Interview with:

Dr. Anne Huml MD Center for Reducing Health Disparities Case Western Reserve University MetroHealth Medical Center Cleveland, Ohio

Dr. Huml

Dr. Anne Huml MD
Center for Reducing Health Disparities
Case Western Reserve University
MetroHealth Medical Center
Cleveland, Ohio 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Overall, about 600,000 Americans have end stage renal disease and require chronic dialysis treatment or a kidney transplant to survive. Compared to chronic dialysis, kidney transplantation results in better survival and quality of life and lower health care costs. Approximately 100,000 patients are listed for a kidney transplant. However, only 17,000 transplants occur per year with two-thirds of these coming from deceased donor organs. Annually, over 8,000 patients either die waiting for a kidney transplant or are removed from the waiting list for being too ill. Waiting times vary based on geography, but it is not unusual for patients to wait upwards of 5 years for a kidney transplant. There are sizeable race, gender, and socioeconomic disparities in access to kidney transplantation.

In this study, we evaluated the outcomes of deceased donor kidney offers and their association with donor and waitlisted patient characteristics. Differences in kidney offer outcomes to patients at the top of the waiting list may contribute to disparities in transplantation.

When a deceased donor organ becomes available, a match run list is created that ranks potential recipients in priority order based upon several characteristics, including waiting time and immunologic criteria. At the discretion of the transplant center, organ offers to patients on their waiting list can be accepted for transplant, or refused for a particular patient. The offers continue down the match run list in sequential order. For each potential recipient in whom the organ is not transplanted, a refusal code is generated and catalogued with the United Network of Organ Sharing, or UNOS. UNOS identifies 37 unique refusal codes and categorizes them into donor-related, transplant center bypassed for pre-specified criteria, recipient-related, histocompatibility-related, program-related, or other reasons for refusal.

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Factors Affecting Interest in Transplant Among ESRD Patients Receiving Dialysis

MedicalResearch.com Interview with:

Deborah Evans, MA, MSW, LCSW Manager, Social Work Services DaVita Kidney Care

Deborah Evans

Deborah Evans, MA, MSW, LCSW
Manager, Social Work Services
DaVita Kidney Care

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: For patients with end-stage renal disease (ESRD) receiving dialysis, receipt of a transplant offers the best possible long-term treatment option. However, the process of becoming qualified to receive a transplant involves many steps, beginning with the patient’s statement of interest.

In this study, we sought to characterize transplant interest among patients in a large dialysis organization in the U.S. and to explore reasons identified by the patients for lack of interest in transplant when applicable.

As of November 2016, of the 182,906 patients with available transplant status information in the LDO database, 58,057 (31.7%) expressed that they were not interested in transplant. Among patients not interested in transplant, the most frequently identified reasons for lack of interest were:

  • Advanced age (25.7%)
  • Perceived poor health (12.0%)
  • Comfortable with current modality (12.0%)
  • Uninterested in further surgeries (11.9%)
  • 13.2% of patients not interested in transplant indicated that “other” factors were responsible for their lack of interest. At the time of the study, we didn’t have any further insight into what might account for these “other” factors.

Compared to patients with transplant status listed as active, those not interested in transplant were:

  • Older (21.4% < 60 years vs 64.6%)
  • More likely to be female (47.7% vs 36.6%)
  • More likely to be white (43.9% vs 30.4%) and less likely to be Hispanic (14.7% vs 22.2%)
  • More likely to be receiving in-center hemodialysis (92.0% vs 73.7%)
  • More likely to have Medicare/Medicaid as primary insurance (91.3% vs. 77.3%)

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Donor Sex and Size Important to Kidney Transplant Success

MedicalResearch.com Interview with:
Amanda Miller, MD, FRCPC

Dalhousie University
Transplant Nephrology

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Earlier studies have shown that there may be a higher risk of kidney transplant failure if a kidney donor is smaller than their recipient. This may be due to increased strain on the relatively smaller transplanted kidney. Very few studies have investigated outcomes associated with donor and recipient weight mismatch measured directly by differences in body weight however. There is also a suggestion that sex mismatch between kidney donor and recipient may lead to worse outcomes post-transplant, however results from earlier studies have been controversial and conflicting. The combined effect of weight and sex matching/mismatching between kidney donor and recipient (two very important and physiologically relevant factors) has not been rigorously studied previously.

Thus, the aim of this study was to determine if receiving a kidney transplant from a smaller donor of the opposite sex would impact transplant outcomes. Accounting for other transplant variables, we demonstrated that if a kidney transplant recipient is more than 30 kg (66 pounds) heavier than the donor there is a 28% increased risk of the transplant failing compared to equally weighted donors and recipients. If the kidney is from a smaller donor of the opposite sex, the risk of transplant failure is further increased to 35% for a male receiving a kidney from a female donor, and 50% for a female receiving a kidney from a male donor. This risk is high and is similar to that when a recipient receives a kidney transplant from a donor who has diabetes; a known risk factor for kidney failure in the non-transplant population.

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Frozen Fecal Transplant in Pill Form Found To Reverse C. Diff Infection

MedicalResearch.com Interview with:

Dr. H. L. DuPont MD Director, Center for Infectious Diseases, UTHealth School of Public Health Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth Professor, Department of Epidemiology, Human Genetics and Environmental Sciences UTHealth School of Public Health Houston, TX 77030

Dr. DuPont

Dr. H. L. DuPont MD
Director, Center for Infectious Diseases, UTHealth School of Public Health
Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth
Professor, Department of Epidemiology, Human Genetics and Environmental Sciences
UTHealth School of Public Health
Houston, TX 77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many diseases and disorders are associated with “dysbiosis,” where the intestinal microbiota diversity is reduced. This contributes to disease and to the acquisition of antibiotic resistance. Fecal microbiota transplantation (FMT) is successful in conditions with pure dysbiosis (e.g. C diff infection) and a single dose of FMT is curative in most cases.

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Two Polyomaviruses Linked To Dermatoses in Immunocompromised Patients

MedicalResearch.com Interview with:

Richard Wang, M.D., Ph.D. Assistant Professor UT Southwestern Medical Center

Dr. Wang

Richard Wang, M.D., Ph.D.
Assistant Professor
UT Southwestern Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:

Currently, there are 13 polyomaviruses known to infect humans. Several members of this family of double-stranded DNA viruses—including Merkel Cell Polyomavirus, Trichodysplasia Spinulosa Polyomavirus, Human Polyomavirus 6 (HPyV6), and Human Polyomavirus 7 (HPyV7)—can be shed from skin of healthy individuals. While most polyomavirus infections are common and subclinical, several polyomaviruses have been associated with debilitating diseases in immunocompromised individuals. Most recently, HPyV7 was discovered in a pruritic and dyskeratotic eruption in two immunosuppressed transplant patients. A closely related polyomavirus, Human Polyomavirus 6, has not yet been strongly linked to any infectious diseases. Using the previously described, characteristic histologic pattern, we identify 3 additional cases of skin eruptions associated with infections of HPyV6 and HPyV7. The association of the dermatoses with highly active infections were confirmed through electron microscopy, immunohistochemistry, quantitative PCR, and complete sequencing. HPyV7 infects keratinocytes and affects their normal differentiation. In addition, next generation sequencing revealed that HPyV6 could persist in a latent state in the skin of a previously infected patient.

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Current Allocation System for Heart Transplantation Might Disfavor Adults with Congenital Heart Disease.

MedicalResearch.com Interview with:

Dr. Laith Alshawabkeh MD ‎Senior Fellow Brigham & Women's and Boston Childrens Hospitals / Harvard Medical School

Dr. Laith Alshawabkeh

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).

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HIV Lymphoma Patients Now Candidates For Stem Cell Transplants

MedicalResearch.com Interview with:

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

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.
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Fecal Microbiota Transplantation is Promising Option for Ulcerative Colitis Treatment

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)

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Three Factors Identify Risk of Fecal Transplant Failure for C. Diff Infections

Monika Fischer, MD, MSCR Assistant Professor of Clinical Medicine Division of Gastroenterology and Hepatology Indiana University Indianapolis, IN 46202

Dr. Monika Fischer

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.

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ESRD Patients May Experience Cardiac Improvement After Transplant

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.

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Study Does Not Support Significant Role of CMV Virus In Transplant Outcomes

MedicalResearch.com Interview with:
Dr. Wilfried Gwinner Div. of Nephrology and Hypertension University of Hanover Medical School Hannover
Dr. 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.
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Why Does Georgia Have the Lowest Rate of Kidney Transplantation?

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. Continue reading

Validation of Noninvasive Tests for Post-Transplant Management of Kidney Graft Recipients

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.

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Wide US Regional Variation In Organ Donation Rates

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.

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Scientists Hope To Use Donor Organs To Engineer Replacement Kidneys

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.
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Active Critical Care Can Increase Number Of Transplant Organs Per Donor

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.
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More Children With SCID Are Now Transplant Candidates

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.
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