Benefits of Transplanting Hepatitis C Infected Livers May Outweigh Risks

MedicalResearch.com Interview with:

Jagpreet Chhatwal, PhD Assistant Professor, Harvard Medical School MGH Institute for Technology Assessment Boston, MA

Dr. Chhatwal

Jagpreet Chhatwal, PhD
Assistant Professor, Harvard Medical School
MGH Institute for Technology Assessment
Boston, MA and

Sumeyye Samur PhD Postdoctoral Fellow MGH-Harvard Medical School

Dr. Samur

Sumeyye Samur PhD
Postdoctoral Fellow
MGH-Harvard Medical School

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

Response: The number of patients who are in need of liver transplant continues to rise whereas the availability of organs remains limited, therefore, it becomes is important to utilize all available livers.

Under the current practices, only Hep-C infected patients are eligible to receive infected livers. However, with the advent of high efficacy drugs, number of infected recipients has decreased over the last decade. On the other hand, with the rise of opioid use, number of Hep-C infected organs increased. With this contradiction, it becomes paramount of importance to utilize the infected livers which could help save more lives on the transplant waiting list.

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Transplant Network Undercaptures Post-Transplant Skin Cancers

MedicalResearch.com Interview with:

Thuzar M.Shin MD, PhD Assistant Professor of Dermatology Hospital of the University of Pennsylvania

Dr. Shin

Thuzar M.Shin MD, PhD
Assistant Professor of Dermatology
Hospital of the University of Pennsylvania

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

Response: The Organ Procurement Transplant Network (OPTN) collects data on cancers that develop after organ transplantation. Previous studies have shown incomplete reporting to the OPTN for many cancers (including melanoma). Skin cancer is the most common malignancy in solid organ transplant recipients and the most common post-transplant skin cancer, cutaneous squamous cell carcinoma (cSCC), is not captured in standard cancer registries. We hypothesized that cSCC and melanoma are underreported to the OPTN. When compared to detailed medical record review obtained from the Transplant Skin Cancer Network database (JAMA Dermatol. 2017 Mar 1;153(3):296-303), we found that the sensitivity of reporting to the OPTN was only 41% for cSCC and 22% for melanoma. The specificity (99% for cSCC and 100% for melanoma) and negative predictive values (93% for cSCC and 99% for melanoma) were high. As a result, the OPTN database is unable to robustly and reliably distinguish between organ transplant recipients with and without these two skin malignancies.

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Microtransplantation Can Be Safe and Effective For Older AML Patients

MedicalResearch.com Interview with:
Huisheng Ai, MD, Director

Department of Hematology and Transplantation,
Affiliated Hospital of the Academy  of Military Medical Sciences,
Beijing, China 

MedicalResearch.com: Which of these results did you find most interesting or surprising?

Response: First, we must stress that microtransplant dramatically improved the outcome of older patients with AML.

As we know, older AML patients often possess unfavorable prognostic factors, organ dysfunction, and slow post-chemotherapy hematopoietic recovery. Therefore, the general treatment outcome is unsatisfactory even though the incidence is increasing by age with low complete remission (CR) rates (34% to 65%) and poor short-term survival (Two years overall survival was about 11% to 25%).

This study involved cases from multiple centers of China, USA and Spain, and found that microtransplant could not only significantly improve complete remission rate in older AML patients among all age groups from 60 to 85, but also improve 1-year and 2-year overall survival and disease free survival especially in patients aged 60 to 75. Second, microtransplant completely overcomes the restriction of HLA typing. The donor could be the patient’s haploidentical family member, or unrelated and fully mismatched one. The incidence of graft-versus-host disease (GVHD) was only 1.1%, even if no any GVHD prevention was given. Other treatment related complications and mortality were also decreased.

These results are much better than those of traditional chemotherapy, myeloablative and non-myeloablative transplant, which provides a more safe and effective treatment choice. We are looking forward to seeing the revision of NCCN guideline for older AML to make microtransplant benefit more older patients.

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IgG Endopeptidase Has Potential To Reduce Kidney Transplant Rejection

MedicalResearch.com Interview with:

Stanley C. Jordan, M.D Director, Division of Nephrology Medical Director, Kidney Transplant Program Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory Cedars-Sinai, Los Angeles, CA

Dr. Jordan

Stanley C. Jordan, M.D
DirectorDivision of Nephrology
Medical DirectorKidney Transplant Program
Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory
Cedars-Sinai, Los Angeles, CA 

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

Response: The background for this study is as follows: Patients who are highly HLA sensitized have antibodies to transplant targets create an immunologic barrier to transplant. Currently, there are no approved therapies for elimination of these antibodies. Desensitization is available but is not always successful and most desensitized patients are still transplanted with a positive crossmatch. Thus, many patients are not able to receive life-saving kidney transplants unless newer therapies to remove antibodies are found.

The findings of our study published in the New England Journal of Medicine revealed that the use of the enzyme from streptococcal pyogenes called IdeS® (IgG endopeptidase) is very effective in eliminating donor specific antibodies and allowing transplantation to occur. Antibodies were eliminated from one week up to two months after one treatment with Ides® allowing a safe environment for the transplant to occur. Rejections episodes did occur in some of the patients but were generally mild and easily treatable. Only one patient of 25 lost his allograft during the study. Thus, the study shows promising results for a new approach for elimination of pathogenic antibodies that did not exist before.

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High Hepatitis C Cure Rate Using Elbasvir plus Grazoprevir In Chronic Kidney Disease

MedicalResearch.com Interview with:

Annette Bruchfeld MD, PhD Senior Consultant Associate Professor Karolinska Institute Dept of Renal Medicine, M99 Karolinska University Hospital Huddinge Stockholm, Sweden

Dr. Bruchfeld

Annette Bruchfeld MD, PhD Senior Consultant
Associate Professor
Karolinska Institute
Dept of Renal Medicine, M99
Karolinska University Hospital Huddinge
Stockholm, Sweden

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

Response: In patients with stage 4–5 chronic kidney disease(CKD), hepatitis C virus (HCV) infection can accelerate the decline in kidney function, impair health-related quality of life (HRQOL), and decrease survival chances of both patients and grafts in transplantation recipients.

In this study additional data from patients with stage 4–5 chronic kidney disease undergoing treatment for HCV infection in the C-SURFER study, including HRQOL and resistance analyses was presented not previously reported for this patient population with gwnotype 1 infection.

The final virological analysis of this study indicated a high cure rate with sustained virological response at 12 weeks after the end of treatment (SVR12) in more than 98% of all treated patients. Even in patients with resistance-associated substitutions (RASs) the SVR was high in 11 (84·6%) of 13 patients genotype 1a infection.

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Food Costs Can Lead To Less Protein and Phosphorous in Indigent Kidney Transplant Patients

MedicalResearch.com Interview with:

Ms. Shifra Mincer Medical Student in the class of 2019 SUNY Downstate Medical School

Shifra Mincer

Ms. Shifra Mincer
Medical Student in the class of 2019
SUNY Downstate Medical School

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

Response: Hypophosphatemia is commonly encountered in the post-transplant setting. Early post-transplant hypophosphatemia has been ascribed to excess FGF23 and hyperphosphaturia.

Many patients remain hypohosphatemic months or even years after their transplant and the mechanism was assumed to be the same, however, our group recently reported that patients with late post-transplant hypophosphatemia had very little phosphorous in their urine (Wu S, Brar A, Markell, MS. Am J Kidney Dis. 2016,67(5): A18). We hypothesized that they were not eating enough phosphorous to compensate for the acute phosphorous losses they experienced immediately post-transplant.

In this study, using both 3-day diet journals and 24-hour diet recall questionnaires, we found that mean intake of phosphorous and protein was barely at the Recommended Daily Allowance, and that despite 70% of the patients using EBT, 30% of those patients still reported concerns regarding food security. Patients who reported that the cost of food influenced their dietary choices ate 43% less protein (average 48,5 gms vs. 85.8 gms) and 29% less phosphorous (average 887 mg vs 1257 mg). When ability to rise from a chair over a 30 second period was evaluated, only patients who expressed food cost concerns were unable to complete the test.

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Comparison of Posttransplant Dermatologic Diseases by Race

MedicalResearch.com Interview with:
Christina Lee Chung, MD, FAAD
Associate Professor of Dermatology
Director, Center for Transplant Patients
Drexel University College of Medicine

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

Response: It’s long been recognized immunosuppressed organ transplant recipients are at significantly increased risk for skin cancer and other types of skin disease.

But despite advances to improve skin cancer prevention for these patients, little is known about how skin conditions affect African-American, Asian and Hispanic transplant recipients. This is problematic given that, according to the U.S. Department of Health and Human Services, more than half of the 120,000 Americans on the waiting list for organs identify as nonwhite.

We compared medical records of 412 organ transplant recipients — including 154 white patients and 258 nonwhite (black, Asian or Hispanic) — who were referred to the Drexel Dermatology Center for Transplant Patients between 2011 and 2016. As one of the only models of its kind in the country, the center provides post-transplant dermatological care to every patient who is transplanted by and/or followed by the Drexel University and Hahnemann University Hospital Transplant Programs. That means that every patient, regardless of race, is screened annually for skin cancer, which provided a unique dataset for us to analyze.

Two hundred eighty-nine transplant recipients exhibited malignant, infectious or inflammatory conditions during their evaluation, but their primary acute diagnoses differed greatly by race. In 82 white patients, skin cancer was the most common acute problem requiring attention at first visit. Black and Hispanic patients, by contrast, were most often diagnosed with inflammatory or infectious processes, such as fungal infections, warts, eczema, psoriasis, and rashes that required immediate medical attention.

Overall, squamous cell carcinoma in situ was the most common type of skin cancer diagnosed in each racial or ethnic group. But the location of the cancerous lesions again depended on the race of the patient. Most lesions in white and Asian patients occurred in sun-exposed areas of the body, like the scalp, neck, chest and back. For black patients, the lesions were primarily found in the groin.  Moreover, six of the nine lesions found on black patients tested positive for high-risk HPV strains, suggesting an association between the virus and skin cancer for African Americans.

We also provided questionnaires to 66 organ transplant recipients to find out more about the patients’ awareness of skin cancer prevention. Seventy-seven percent of white patients were aware their skin cancer risk was increased, compared to 68 percent of nonwhites. Only 11 percent of nonwhite patients reported having regular dermatologic examinations, compared to 36 percent of whites. Finally, 45 percent of white patients but only 25 percent of nonwhite reported knowing the signs of skin cancer.

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Tocilizumab High Active For Refractory Graft vs Host Disease

MedicalResearch.com Interview with:

Dr. Alex Ganetsky

Dr. Alex Ganetsky

Alex Ganetsky, PharmD, BCOP
Clinical Pharmacy Specialist – Hematology/BMT
Hospital of the University of Pennsylvania

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

• Allogeneic hematopoietic cell transplant (HCT) recipients with steroid-refractory gastrointestinal acute graft-versus-host disease (GI-GVHD) have poor outcomes.
• There is no consensus for optimal treatment of these patients.
• We retrospectively evaluated the efficacy of tocilizumab, an interleukin-6 receptor monoclonal antibody, for the treatment of steroid-refractory GI-GVHD.
• 10/11 (91%) patients achieved a complete response after a median time of 11 days (range, 2 – 18) from tocilizumab initiation.
• The median time to response onset, defined as improvement in GVHD stage by at least 1, was 1 day (range, 1 – 6).
• At a median follow-up of 3 months (range, 1.1 – 12.8) from tocilizumab initiation, 8 of 11 patients are alive and free of the their underlying hematologic malignancy.
• No associations between serum levels of IL-6 and tocilizumab response could be identified.
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A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults

MedicalResearch.com Interview with:
Adam Johnson, MD, PhD, MBA, FACS

Thomas Jefferson University

Dr. Cataldo Doria, senior author and designer of the study, emphasized that the work was a team effort

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

Response: The goal was to develop an algorithm to identify which donors would be most suitably transplanted as dual kidneys instead of as single kidneys.

Dual kidney transplantation is a resource intensive procedure, but may make the most out of two kidneys whose function may be too marginal to transplant independently.

Currently allocation decisions are based on individual surgeon and institutional experience and without much available outcome data. This score provide decision support for which donor grafts would have the greatest benefit if transplanted as dual kidneys.

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Three Criteria To Identify Out-of-Hospital Cardiac Arrest Patients With No Chance of Survival

MedicalResearch.com Interview with:

Prof. Xavier Jouven Service de Cardiologie Hôpital Européen Georges Pompidou Paris

Prof. Xavier Jouven

Prof. Xavier Jouven
Service de Cardiologie
Hôpital Européen Georges Pompidou
Paris

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

Response: There are many cardiac arrests (around 300 000 per year in United States). The possibility to collect organs from a certain proportion of those cardiac arrests represents an important opportunity to fill the gap of the organ shortage.

It is absolutely mandatory to identify patients with no chance of survival. This study showed 3 criteria which allow this early identification. Several thousands of patients die every year waiting for organ transplantation.

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