Kidney Transplant Patients at Increased Risk of Skin Cancer, Even After Graft Stops Working

MedicalResearch.com Interview with
"Kidney Model 9" by GreenFlames09 is licensed under CC BY 2.0. To view a copy of this license, visit: https://creativecommons.org/licenses/by/2.0Donal JSextonMD, PhD
Department of Nephrology and Kidney Transplantation
Beaumont Hospital
Royal College of Surgeons in Ireland
Dublin, Ireland

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

Response: Patients who receive a kidney transplant as treatment for end stage kidney disease are at risk of malignancy due to immunosuppression. In contrast to

other solid organ transplant types, when kidney transplants fail it is possible for recipients to return to dialysis. Immunosuppression is usually reduced or completely stopped when  the allograft fails due to the risk of infection on dialysis.

We decided to investigate what the trajectory of risk for non-melanoma skin cancer and invasive cancers overall (composite group) looked like for patients who have received multiple consecutive kidney transplants with intervening periods of graft failure. We compared cancer risk during periods of allograft failure and periods of functioning kidney transplants.   Continue reading

First Blood Test To Predict Lung Transplant Rejection

MedicalResearch.com Interview with:

Sean Agbor-Enoh, M.D., Ph.D. Co-Director/Staff Clinician Laboratory of Transplantation Genomics National Heart, Lung, and Blood Institute National Institutes of Health

Dr. Agbor-Enoh

Sean Agbor-Enoh, M.D., Ph.D.
Co-Director/Staff Clinician
Laboratory of Transplantation Genomics
National Heart, Lung, and Blood Institute
National Institutes of Health

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

Response: People who receive organ transplants may develop acute or chronic rejection, in which the body’s immune system attacks the transplanted organ. While acute rejection is treatable and reversible, chronic rejection is not and remains the most common cause for organ transplant loss. Lung transplant recipients have the shortest survival rates among patients who get solid organ transplantation of any kind—only about half live past five years. This poor survival rate among lung transplant recipients is due in part to a high incidence of chronic rejection. Existing tools for detecting signs of rejection, such as biopsy, either require the removal of small amounts of lung tissue or are not sensitive enough to discern the severity of the rejection.

Building upon earlier work, our research team developed a simple blood test that can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of the rejection are evident.  The test could make it possible for doctors to intervene faster to prevent or slow down so-called chronic rejection—which is severe, irreversible, and often deadly—in those first critical months after lung transplantation. This same test might also be useful for monitoring rejection in other types of organ transplants.

Called the donor-derived cell-free DNA test, the experimental test begins with obtaining a few blood droplets taken from the arm of the transplant recipient. A special set of machines then sorts the DNA fragments in the blood sample, and in combination with computer analysis, determines whether the fragments are from the recipient or the donor and how many of each type are present.  Because injured or dying cells from the donor release lots of donor DNA fragments into the bloodstream compared to normal donor cells, higher amounts of donor DNA indicate a higher risk for transplant rejection in the recipient.

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Vaccine Preventable Infections Common After Pediatric Organ Transplantation

MedicalResearch.com Interview with:

Amy G. Feldman, MD, MSCS Assistant Professor, Pediatrics-Gastroenterology, Hepatology and Nutrition Program Director, Liver Transplant Fellowship Children's Hospital Colorado  University of Colorado Medicine

Dr. Feldman

Amy G. Feldman, MD, MSCS
Assistant Professor, Pediatrics-Gastroenterology, Hepatology and Nutrition
Program Director, Liver Transplant Fellowship
Children’s Hospital Colorado
University of Colorado Medicine

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

Response: Pediatric solid organ transplant recipients are at increased risk for vaccine preventable infections due to life-long immunosuppressive medications.  The objectives of this study were to 1) evaluate in pediatric    solid organ transplant recipients the number of hospitalizations for vaccine-preventable infections in the first five years post-transplantation and 2) determine the associated morbidity, mortality and costs.

In this multicenter cohort study of 6980 children who underwent solid organ transplantation from January 1, 2004, to December 31, 2011, at a center participating in Pediatric Health Information System (PHIS), 15% of individuals had at least 1 hospitalization for a vaccine-preventable infection in the first 5 years after transplant.  Children who received transplants when they were younger than 2 years and recipients of lung, intestine, heart, and multi-visceral organs were at increased risk for hospitalization with a vaccine-preventable infection.  Transplant hospitalizations complicated by a vaccine-preventable infection were $120,498 more expensive (median cost) and were on average 39 days longer than transplant hospitalizations not complicated by vaccine-preventable infections Continue reading

Children Undergoing Bone Marrow Transplant Remain At Risk For Premature Death

MedicalResearch.com Interview with:

Smita Bhatia, MD, MPH Gay and Bew White Endowed Chair in Pediatric Oncology Professor, Pediatric Oncology Vice Chair for Outcomes Research, Dept of Pediatrics Director, Institute for Cancer Outcomes and Survivorship School of Medicine University of Alabama at Birmingham Associate Director for Outcomes Research UAB Comprehensive Cancer Center 

Dr. Bhatia

Smita Bhatia, MD, MPH
Gay and Bew White Endowed Chair in Pediatric Oncology
Professor, Pediatric Oncology
Vice Chair for Outcomes Research, Dept of Pediatrics
Director, Institute for Cancer Outcomes and Survivorship
School of Medicine
University of Alabama at Birmingham
Associate Director for Outcomes Research
UAB Comprehensive Cancer Center 

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

Response: Allogeneic bone marrow transplantation BMT is used with a curative intent for life-threatening malignant and non-malignant diseases of childhood.

In this observational study, we describe the late mortality experienced by children undergoing BMT over the past 3 decades. Our cohort included 1388 BMT recipients who had undergone allogeneic BMT between 1974 and 2010 and survived 2 or more years.

We found that, conditional on surviving the first 2 years after bone marrow transplantation, the probability of surviving an additional 20 years approached 80%. Risk of dying from non-relapse-related causes exceeded the risk of dying from relapse-related causes.

The leading non-relapse-related causes of death were infection (with or without graft vs. host disease) and new cancers. Overall, the cohort was at a 14-fold greater risk of dying as compared with the general population (of similar age and sex). Further, this excess risk remained elevated even among those who had survived 25 years.

On a positive note, the risk of late mortality has continued to decline over the past 3 decades. 

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Organ Transplant Recipients Require Vigilant Sun Protection

MedicalResearch.com Interview with:
“Sunscreen” by Tom Newby is licensed under CC BY 2.0Rebecca Ivy Hartman, M.D
Instructor in Dermatology
Brigham and Women’s Hospital
Boston MA 02115

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

Response: Organ transplant recipients (OTR) are at 100-fold higher risk to develop certain skin cancers compared to the general population due to immunosuppression, and thus preventing skin cancer in this population is critical.

Our study found that in a high-risk Australian OTR population, only half of patients practiced multiple measures of sun protection regularly.

However, after participating in a research study that required dermatology visits, patients were over 4-times more likely to report using multiple measures of sun protection regularly. Patients were more likely to have a positive behavioral change if they did not already undergo annual skin cancer screening prior to study participation.

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Early Study Demonstrates Airways Can Be Transplanted from Aortic Templates

MedicalResearch.com Interview with:
Emmanuel Martinod MD PhD
Assistance Publique–Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Hôpital Avicenne, Chirurgie Thoracique et Vasculaire, Université Paris 13, Sorbonne Paris Cité, UFR Santé, Médecine et Biologie Humaine, Bobigny,
Université Paris Descartes, Fondation Alain Carpentier, Laboratoire de Recherche Bio-chirurgicale, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou
Paris, France 

MedicalResearch.com: What is the background for this exciting new technology and study? What are the main findings? 

Response: What is the background for this exciting new technology and study? What are the main findings?

Response:  The background is 10 years of research at laboratory followed by 10 years of academic clinical research.

We demonstrated the feasability of airway bioengeenring using stented aortic matrices for complex tracheal or bronchial reconstruction.  Continue reading

Pre-Emptive Therapy of CMV in Allogeneic Hematopoietic Cell Transplant

MedicalResearch.com Interview with:

 Dr-Roy F. Chemaly

Dr. Chemaly

Roy F. Chemaly, MD, MPH F.A.C.P., F.I.D.S.A.
Department of Infectious Diseases
Infection Control and Employee Health
Division of Internal Medicine
MD Anderson Center

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

Response: CytomegalovirusCMV infection is a common cause of morbidity and mortality in allo-HCT recipients. Evidence suggests that CMV infection has not only an enormous clinical burden, but a substantial economic burden as well.

We conducted this study at MD Anderson to determine the economic and clinical burden of preemptive therapy (PET) for CMV infection. Between 2012 and 2015, 100 consecutive patients hospitalized at our institution for allo-HCT who experienced reactivation of CMV and were treated pre-emptively, were enrolled.

The majority of patients were men (55%), who had underlying leukemia (73%), and underwent matched unrelated donor transplant (59%). At the time of hospitalization, most patients had acute GvHD (62%), and were on steroids (58%) within 30 days of CMV reactivation which occurred at a median of 32 days post-HCT (2 -174). A total of 192 episodes of PET occurred in the 100 allo-HCT recipients within 1 year post-HCT. PET consisted of ganciclovir (41%), foscarnet (40%), and valganciclovir (38%). IVIG was also used as adjunct therapy in 20% of episodes.

Progression to Cytomegalovirus disease occurred in 4 patients (4%) and mainly affected the GI tract. Mean length of stay for patients treated with ganciclovir or foscarnet was 32 days (2-141) and 41 days (1-177), respectively. The average direct cost per patient admitted for PET was $126,038 ($7,866-$641,841) and the mean cost of CMV antiviral drug per hospitalization was $6,096 for IVIG, $2,410 for foscarnet, $836 for ganciclovir, and $780 for valganciclovir.

Serious side effects from PET were observed in 35% of patients on ganciclovir and 12% of patients on foscarnet. Total direct cost per encounter was significantly higher in patients who had serious side effects from foscarnet. All-cause mortality was 59% at 1 year post-transplant.

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Double-Edge Sword of Drug Epidemic

MedicalResearch.com Interview with:
Christine Marie Durand, M.D
.
Assistant Professor of Medicine
Johns Hopkins Medicine 

MedicalResearch.com: What is the background for this study

Response: Most Americans know that the United States faces an epidemic of deaths due to drug overdose.  And many are also aware that there is a critical shortage of organs available for transplant.  Perhaps less widely known is that today, more than 1 in every 8 deceased organ donors died from a drug overdose.  The objective of our study was to look at the outcomes of patients who received transplants with organs donated after an overdose.

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Electronic Pillbox May Improve Adherence To Complicated Medication Regime

MedicalResearch.com Interview with:

Bethany J. Foster, MD MSCE Montreal Children’s Hospital Department of Pediatrics,  Department of Epidemiology, Biostatistics, and Occupational Health McGill University, Montreal, QC, Canada

Dr. Foster

Bethany J. Foster, MD MSCE
Montreal Children’s Hospital
Department of Pediatrics,
Department of Epidemiology, Biostatistics, and Occupational Health
McGill University, Montreal, QC, Canada

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

Response: Adolescent and young adult kidney transplant recipients have the highest risk of graft loss of any age group. One of the main reasons for this is not taking their anti-rejection medications as prescribed. Our study had the goal of testing an intervention to try to improve young patients’ adherence to their strict medication schedule. The intervention included feedback of how well they were taking their medications (which was monitored electronically), text message reminders for medication doses, and individualized coaching to address their personal barriers to taking their medications.

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Umbilical Cord Blood Stem Cells May Improve Symptoms in Children with Autism

MedicalResearch.com Interview with:

Michael G. Chez, M.D. Director of Pediatric Neurology Sutter Memorial Hospital Director of the Pediatric Epilepsy and Autism Programs Sutter Neuroscience Group 

Dr. Michael Chez

Michael G. Chez, M.D.
Director of Pediatric Neurology Sutter Memorial Hospital
Director of the Pediatric Epilepsy and Autism Programs
Sutter Neuroscience Group 

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

Response: The study looked at possible use of autologous cord blood as a source of stem cells in patients with autism. The patients had to have fairly good genetic screening per protocol and had confirmation of autism to participate.

The use of cord blood was a pilot cross over double blind study with hypothesis that a post natal factor or immune dysregulation may add to the autism clinical phenotype.

Cord blood ( the baby’s own from birth) is a safe source of mixed stem cell types and should be safe from rejection or autoimmune reaction in theory.

Infusion /placebo or placebo/infusion was randomized and observed and tested every 3 months with switch to other wing of treatment at 0 and 6 months. Total observation was over 1 year.

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Potentially Cancerous Genital Lesions Common in Transplant Population

MedicalResearch.com Interview with:

Dr. Christina Lee Chung, MD Associate Professor Department of Dermatology Drexel University

Dr. Chung

Dr. Christina Lee Chung, MD
Associate Professor
Department of Dermatology
Drexel University

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

Response: In early 2016, five years after the inception of our specialty medical-surgical transplant dermatology center, we realized our nonwhite transplant patients were developing skin cancer at higher rates and found interesting trends. These data were published in a previous manuscript. One of the more striking findings was that these patients were developing a high proportion of skin cancer in non-sun-exposed areas such as the genital region. There are no standard guidelines regarding genital skin evaluation and it is unclear how often it is performed in any capacity amongst dermatologists, including practitioners in our center, quite frankly. Our group was concerned that we could be missing skin cancers in this “hidden” area in our high-risk organ transplant population so we launched a quality improvement initiative that incorporated thorough genital skin evaluation as a standard part of post-transplant skin cancer screening.   

Fifteen months after we started this modified screening process, we decided to evaluate the results. To account for any variation in examination, we looked at the findings of a single practitioner.

We found that genital lesions are common in the transplant population and include high rates of genital warts and skin cancer. However, patient awareness of the presence of genital lesions was alarmingly low. Nonwhite transplant patients, Black transplant recipients in particular, were disproportionately affected by both genital warts and genital skin cancer in our cohort. Similar to cervical cancer, high-risk HPV types were closely associated with genital squamous cell carcinoma development in our transplant population. Continue reading

What Are The Health Risks To Living Kidney Donors?

Emanuele Di Angelantonio MPhl Department of Public Health and Primary Care School of Clinical Medicine University of Cambridge 

Emanuele Di Angelantonio

MedicalResearch.com Interview with:
Emanuele Di Angelantonio MPhl

Department of Public Health and Primary Care
School of Clinical Medicine
University of Cambridge 

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

Response: This systematic review supports and expands previous research suggesting that living kidney donors have no increased risk for several major chronic diseases, with the exception of end stage renal disease. Female donors seem to be at increased risk for preeclampsia. Furthermore, there was no evidence that living kidney donors had higher risk for mortality, cardiovascular disease, or type 2 diabetes, or reduced quality of life. –

MedicalResearch.com: What should readers take away from your report?

Response: This study highlights the low but real risks of living kidney donation and emphasise the importance of careful assessment and counseling for all living kidney donors. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: While this systematic review and meta-analysis provide some important answers, the field is still a long way from offering precise risk estimates to prospective donors.  

No disclosures 

Citations:

O’Keeffe LM, Ramond A, Oliver-Williams C, Willeit P, Paige E, Trotter P, et al. Mid- and Long-Term Health Risks in Living Kidney DonorsA Systematic Review and Meta-analysis. Ann Intern Med. [Epub ahead of print 30 January 2018] doi: 10.7326/M17-1235

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Despite 20 Years of Programs and Policies, Racial Disparities in Kidney Transplants Widen

MedicalResearch.com Interview with:

Tanjala S. Purnell, PhD MPH Assistant Professor of Surgery, Epidemiology, and Health Behavior and Society Core Faculty, Epidemiology Research Group in Organ Transplantation Johns Hopkins University Associate Director for Education and Training, Johns Hopkins Center for Health Equity Member, OPTN/UNOS Minority Affairs Committee

Dr. Purnell

Tanjala S. Purnell, PhD MPH
Assistant Professor of Surgery, Epidemiology, and Health Behavior and Society
Core Faculty, Epidemiology Research Group in Organ Transplantation
Johns Hopkins University
Associate Director for Education and Training, Johns Hopkins Center for Health Equity
Member, OPTN/UNOS Minority Affairs Committee 

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

  • Our study was motivated by the fact that we know live donor kidney transplants are associated with longer life expectancy and higher quality of life than deceased donor kidney transplants or long-term dialysis treatment. We also know that Black and Hispanic adults are more likely than White adults to have end-stage kidney disease but are less likely than White patients to receive live donor kidney transplants.
  • Over the last 2 decades, there have been several transplant education programs implemented within transplant centers and dialysis centers, and legislative policies enacted to improve overall access to live donor kidney transplants for patients. We wanted to see whether these programs and policies resulted in narrowed racial and ethnic disparities in access to live donor kidney transplants in the United States. 

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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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