Category: Transplants

Categories : Respiratory Diseases TransplantsTags :

Better Transplant Outcomes from Slightly Warmer Donor Lungs

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Storing donor lungs for transplant at 10°C markedly increases the length of time the organ can live outside the body, according to results of a trial were published in the New England​ Journal of Medicine Evidence. These findings will help reduce the strain on hospitals, reduce waitlists and possibly eliminate the need to bump other surgeries for a lung transplant.

The multicentre, non-randomised clinical trial study of 70 patients demonstrated that donor lungs remained healthy and viable for transplant up to four times longer compared to storage at the current standard of ice cooler preservation of around 4°C. The study was led by a team of scientists at the Toronto Lung Transplant Program in UHN’s Ajmera Transplant Centre.

“The clinical impact of this study is huge,” says lead author Dr Marcelo Cypel, Surgical Director of the Ajmera Transplant Centre and a surgeon within UHN’s Sprott Department of Surgery.

“It’s a paradigm shift for the practice of lung transplant.​ I have no doubt that this will become the gold standard practice of lung preservation for the foreseeable future.”

Lungs available for transplant are currently limited by the length of time a donor organ can be kept viable. Increasing storage time allows for viable donor lungs to come from greater distances, increasing the potential for greater numbers of lungs becoming available for transplant and overcoming many of the hurdles around transplant logistics.

“In transplant, we still see a critical shortage of organs and people dying on the waitlist because there are not enough lungs to be transplanted,” says Dr Cypel, who is also a professor in the Division of Thoracic Surgery, Department of Surgery at the University of Toronto.

“It’s a great accomplishment to see that our research is now having an impact, and that we can actually have more cases done at our centre, with continued outstanding clinical results.

“Better organ preservation also means better outcomes for patients.”

Transplant surgeries could become planned procedures

The trial took place over 18 months at UHN’s Toronto General Hospital, the Medical University of Vienna, and Hospital Universitario Puerta de Hierro-Majadahonda in Madrid.

“The ability to extend the lifespan of the donor organ poses several advantages,” says study first author Dr Aadil Ali, adjunct scientist at the Toronto General Hospital Research Institute.

“Ultimately, these advantages will allow for more lungs to be utilised across farther geographies and the ability to improve recipient outcomes by converting lung transplantation into a planned rather than urgent procedure.”

Some advantages of this new 10°C standard for lung storage include the potential to reduce or eliminate the 24/7 schedule and urgency of lung transplant procedures. By increasing the length of time donor lungs are viable, transplant surgeries could become planned procedures, which avoids bumping scheduled surgeries and overnight transplantation.

The study also suggests the new preservation temperature will allow more time to optimise immunologic matching between donor and recipients, and the possibility of performing lung transplantation in a semi-elective rather than urgent fashion.

For more on the study, watch Dr Marcelo Cypel’s presentation of findings at a recent American Association for Thoracic Surgery event.

Also, watch a video with Drs Cypel and Ali discussing the foundational work leading to this breakthrough.

Source: University Health Network

Categories : TransplantsTags :

Groote Schuur Performs Africa’s First ABO-incompatible Kidney Transplant

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Anatomic model of a kidney
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Eyewitness News reports that doctors at Groote Schuur Hospital have successfully performed Africa’s first incompatible kidney transplant. Known as ABO-incompatible (ABOi) transplants, these procedures are done when the donor’s blood type does not match the recipient’s – once a major contraindication.

The patient, a 35 year old woman named Chervon Meyer, received a kidney donation from her brother. She had been on dialysis for 10 years,

Over half a century ago, Groote Schuur had its mark on history with the world’s first human heart transplant led by Dr Christiaan Barnard.

Incompatible living kidney transplants have long been contraindicated because of the presence of isohaemagglutinins, natural antibodies reacting with non-self ABO antigens. Due to the growing demand for transplant organs, incompatible donations were investigated in order to expand the pool of possible donors. This has changed with the development of new desensitisation regimens over the past decades. These include immunoadsorption and plasmapheresis and the immunosuppressive protocol.

The improvements have been so great that, despite a lack of randomised trials, recent meta analysis found that there is no difference in terms of graft and patient’s survival between ABOi and ABO compatible kidney transplant, even in the long term.

As nephrologist Dr Zunaid Barday explains, this procedure made use of a Glycosorb filter which reduced many of the risks associated with desensitisation, such as plasma exchange weakening the immune system. It works by binding anti-A and anti-B antibodies, reducing their levels in blood plasma. While expensive, the filter is a much cheaper alternative in the long run compared to years of dialysis.

Source: Eyewitness News

Categories : Diet and Nutrition TransplantsTags :

Is Protein Restriction the Best Option after Kidney Transplant?

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Anatomic model of a kidney
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Scientists at Osaka Metropolitan University have challenged the conventional wisdom that low protein intake is essential for kidney disease patients with their recent study on the relationship between protein intake and skeletal muscle mass in kidney transplant recipients. Their findings were published in Clinical Nutrition.

Chronic kidney disease patients are known to have induced sarcopenia due to chronic inflammation, hypercatabolism, decreased nutrient intake, and decreased physical activity associated with impaired kidney function. A successful kidney transplantation is able to correct or improve many of those physiological and metabolic abnormalities, with the transplant recipients increasing skeletal muscle mass after receiving their new kidney. Since excessive protein intake worsens kidney function, it is commonly believed that patients with chronic kidney disease, including kidney transplant recipients, should limit protein intake to protect their kidneys. On the other hand, it has been suggested that severe protein restriction may worsen sarcopenia and adversely affect prognosis.

Since nutrition and exercise therapy are recommended to improve sarcopenia, protein intake is suspected to relate to recovery of skeletal muscle mass after kidney transplantation. However, few studies have examined the relationship between skeletal muscle mass and protein intake in kidney transplant recipients.

In order to fill this knowledge gap, a research group led by Drs Akihiro Kosoku and Tomoaki Iwai, and Professor Junji Uchida at Osaka Metropolitan University followed 64 kidney transplant recipients for 12 months after their procedure. They investigated the relationship between changes in skeletal muscle mass, as measured by bioelectrical impedance analysis, and protein intake from urine sample. The results showed that changes in skeletal muscle mass during this period were positively correlated with protein intake, and that insufficient protein intake resulted in decreased muscle mass.

Drs Iwai and Kosoku commented, “To improve the life expectancy of kidney transplant recipients, further research is needed to clarify the optimal protein intake to prevent either deterioration in kidney function or sarcopenia. We hope that nutritional guidance, including protein intake, will lead to improved life expectancy and prognosis.”

Source: Osaka Metropolitan University

Categories : Cancer TransplantsTags :

Excellent Outcomes for Shrinking Liver Cancer Tumours Before Transplant

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Shrinking liver cancer tumours in order to allow the patient to qualify for a liver transplant leads to excellent 10-year post-transplant outcomes, according to the findings of a new study published in JAMA Surgery. The results validate current US policies around transplant eligibility.

Selection of patients with hepatocellular carcinoma (HCC), the most common form of liver cancer, for transplant has been guided for more than two decades by standards known as the Milan criteria. The Milan criteria state that transplantation should be performed in those with a single tumour of 5cm or less in diameter or three tumours that are each 3cm or less in diameter, have no macrovascular invasion, and no metastasis. Over time, the rising incidence of HCC and mortality rates in the United States have led to refinements to the selection policy, shifting the focus to guidelines that also incorporate tumour biology, response to bridging therapies, and waiting times for patients within and beyond the Milan criteria.

One aspect of the current criteria is known as downstaging: the process of applying liver directed therapy to tumours too big for the Milan criteria with the hope of reducing them to the suggested size. Downstaging is now an option in selecting suitable liver transplant candidates with initial tumors that exceed the criteria. However, liver cancer can recur after transplantation, either within or outside the liver. The treatment options of patients who have recurrence post transplantation is limited and prognosis is poor.

In this cohort study, a retrospective multicentre analysis of prospectively collected data was conducted for 2645 adults who had undergone liver transplant for HCC at five centres between January 2001 and December 2015. The outcomes of 341 patients whose disease was downstaged to fit within the Milan criteria were compared with those in 2122 patients whose disease always fit within the criteria and 182 patients whose disease was not downstaged.

The 10-year post-transplant survival and recurrence rates were, respectively, 52.1% and 20.6% among those whose disease was downstaged; 61.5% and 13.3% in those always within the criteria; and 43.3% and 41.1% in those whose disease was not downstaged.

“Our study validates national policy on downstaging prior to transplantation and shows the clear utility benefit for transplantation prioritisation decision-making,” said Parissa Tabrizian, MD, co-lead author on the study. “These results can increase the level of recommendations for the downstaging policy on a global basis. It also demonstrates that surgical management of HCC recurrence after transplantation is associated with improved survival in well-selected patients and should be pursued. The study also supports expanding the policy of downstaging applied to guidelines in Europe and Asia.”

“Our study represents a solid confirmation that HCC patients effectively downstaged to Milan criteria have an outstanding median survival of 10 years, thus providing the rationale to adopt this policy on a global basis,” said Josep Llovet, MD, PhD, co-lead author on the study. “With this study clinical practice guidelines of management of HCC can recommend our approach with an acceptable level of evidence.”

Source: The Mount Sinai Hospital

Categories : Paediatrics TransplantsTags :

Paediatric Kidney Transplants without Immunosuppressive Drugs

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Anatomic model of a kidney
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Stanford Medicine physicians have developed a way to provide paediatric kidney transplants without immunosuppressive drugs. Their key innovation is a safe method to transplant the donor’s immune system to the patient before surgeons implant the kidney.

The medical team has dubbed the two-transplant combination a “dual immune/solid organ transplant,” or DISOT. The first three DISOT cases, all performed at Lucile Packard Children’s Hospital Stanford were described in the New England Journal of Medicine, accompanied by an an editorial about the research.

The Stanford innovation removes the possibility that the recipient will experience immune rejection of their transplanted organ, the most common reason for a second organ transplant The new procedure also rids recipients of the substantial side effects of a lifetime of immune-suppressing medications, including increased risks for cancer, diabetes, infections and hypertension.

“Safely freeing patients from lifelong immunosuppression after a kidney transplant is possible.”

Alice Bertaina, MD, PhD, report’s lead author, associate professor of paediatrics, Stanford University

The first three DISOT patients were children with a rare immune disease, but the team is expanding the types of patients who could benefit. The protocol received FDA approval on May 27, 2022, for treating patients with a variety of conditions that affect the kidneys. Dr Bertaina anticipates that the protocol will eventually be available to many people needing kidney transplants, starting with children and young adults, and later expanding to older adults. The researchers also plan to investigate DISOT’s utility for other types of solid-organ transplants.

The scientific innovation from Dr Bertaina’s team has another important benefit: It enables safe transplantation between a donor and recipient whose immune systems are genetically half-matched, meaning children can receive stem cell and kidney donations from a parent.

The advance is especially meaningful for Jessica and Kyle Davenport of Muscle Shoals, Alabama. Their two children, both born with a rare and potentially deadly immune disease, are among the first recipients of DISOT: 8-year-old Kruz received transplants from Jessica, while his 7-year-old sister, Paizlee, received transplants from Kyle.

“They’ve healed and recovered, and are doing things we never thought would be possible,” said Jessica Davenport. After years of helping Kruz and Paizlee cope with severe immune deficiency and its attendant infection riskk as well as kidney dialysis, she and her husband are thrilled that their children have more normal lives.

The idea of transplanting a patient with their organ donor’s immune system has been around for decades, but it has been difficult to implement. Transplants of stem cells from bone marrow provide the patient with a genetically new immune system, as some of the bone marrow stem cells mature into immune cells in the blood. First developed for people with blood cancers, stem cell transplants carry the risk of the new immune cells attacking the recipient’s body, a potentially lethal complication called graft-versus-host disease.

Source: Stanford Medicine

Categories : Obstetrics & Gynaecology TransplantsTags :

Uterus Transplants are Safe and Effective, Study Finds

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The world’s first complete study of living donor uterine transplantation, published in the journal Fertility and Sterility, has found that it is an effective, safe method to remedy infertility when a functioning uterus is lacking.

After seven of the study’s nine transplants, in vitro fertilisation (IVF) treatment ensued. In this group of seven women, six (86%) became pregnant and gave birth. Three had two children each, making the total number of babies nine.

In terms of what is known as the ‘clinical pregnancy rate’, the study also showed good IVF results. The probability of pregnancy per individual embryo returned to a transplanted uterus was 33%, about the same as for typical IVF.

Participants followed up

Few cases were studied, the researchers observed, but the material is the world best and included extensive, long-term follow-ups of participants’ physical and mental health.

None of the donors had pelvic symptoms but, in a few, the study describes mild, partially transient symptoms in the form of discomfort or minor swelling in the legs.

After four years, health-related quality of life in the recipient group as a whole was higher than in the general population. Neither members of the recipient group nor the donors had levels of anxiety or depression that required treatment.

Growth and development of the children were monitored as well, up to age two and is, accordingly, the longest child follow-up study conducted to date in this context. Further monitoring is planned to adulthood.

Good health in the long term

“This is the first complete study that’s been done, and the results exceed expectations in terms both of clinical pregnancy rate and of the cumulative live birth rate,” said study leader Mats Brännström, professor of obstetrics and gynaecology at Sahlgrenska Academy, University of Gothenburg.

“The study also shows positive health outcomes: The children born to date remain healthy and the long-term health of donors and recipients is generally good too.”

The first birth after uterine transplantation took place in Gothenburg in 2014. Another seven births followed, within the framework of the same research project, before anyone outside Sweden gave birth following uterine transplantation.

The research group has since passed on its methods and techniques through direct knowledge transfer to several research centres outside Sweden. By the end of 2021, there were an estimated 90 uterine transplants worldwide, of which 20 had been done in Sweden. Worldwide, some 50 children have been born after uterine transplantation.

Source: University of Gothenburg

Categories : Ethics and Law TransplantsTags :

Experimental Surgeon Convicted for Tracheal Implant Death

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A Swedish court has convicted Paolo Macchiarini, a formerly lauded trachea surgeon, of causing bodily harm to a patient through negligence during a highly experimental stem-cell trachea transplant. For this, the court handed down a two-year probational sentence. He was acquitted of assault charges on two other patients; all three died in the months and years after the surgeries.

In 2010, Macchiarini was hired by the Karolinska Institute (KI) and the Karolinska University Hospital to support Sweden’s regenerative medicine innovation. His specialty was replacing damaged tracheae with artificial ones that combined stem cells with polymer scaffolds or decellularised donor tracheae. Starting in 2011, he began operating on patients as an experimental life-saving measure but his work at at KI was suspended in 2013 after the second of his three patients died. However, he continued performing surgeries in Russia.

Yet there were already hints that something was amiss even before the first surgeries. In 2011, another academic, Pierre Delaere of UZ Leuven in Belgium accused Macchiarini of misrepresenting research findings in published articles. In 2012, Macchiarini was arrested in Italy and charged with fraud and attempted extortion. 

By 2014, after the death of his first patient, three separate allegations were raised of scientific misconduct in reporting the cases. He would later be cleared of these, but in 2016 a TV documentary called ‘The Experiment’ described the suffering and deaths patients of failed artificial tracheas transplants, and raised many issues concerning care and research ethics. The severe public backlash caused KI to launch another investigation into Macchiarini, amid an upheaval which saw a string of resignations and an overhaul of hiring and ethics. He was found to have falsified his CV, and published papers with false or misleading data that were subsequently retracted. By March, he had been fired and criminal charges filed against him.

BBC News reported that at least seven people had died following the surgeries. In 2018, KI found seven researchers guilty of academic misconduct. Swedish authorities decided to reopen investigations into the three deaths.

Matthias Corbascio, a cardiac surgeon at KI who testified in the trial, told SVT Nyheter that he doesn’t believe justice has been done. “My reaction is that it is very meager. It is a terrible scandal and terrible for the patients’ families that he could get away so easily,” he said.

Chief judge Bjoern Skaensberg said the court had agreed with prosecutors that the surgery had not been consistent with “science and proven experience”. However, he told public broadcaster SVT that it had concluded that “two of the interventions were justifiable, but not the third”.

The court had found that all three patients had suffered serious bodily injury, Judge Skaensberg said. But Macchiarini was cleared of assault as no intent to harm had been proven.

Macchiarini had always denied any wrongdoing, arguing that the transplants were aimed at saving the patients’ lives.

However, whistleblower Dr Matthias Corbascio told SVT that the verdict was a scandal and there had never been any chance of the operations succeeding.

The suspended sentence means he will be on probation for the next two years.

Source: BBC News

Categories : Cancer TransplantsTags :

Living Donors Liver Transplant a Viable Option in Colorectal Cancer

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A recent study published in JAMA Surgery has demonstrated the viability of living-donor liver transplant for patients who have systemically controlled colorectal cancer and liver tumours that cannot be surgically removed.

“This study proves that transplant is an effective treatment to improve quality of life and survival for patients with colorectal cancer that metastasised to the liver,” said senior study author Dr Gonzalo Sapisochin.

The study focused on colorectal cancer partly for its tendency to spread to the liver. Nearly half of all patients with colorectal cancer develop liver metastases within a few years of diagnosis and 70% of liver tumours in these patients cannot be removed without removing the entire liver.

Unfortunately, most of these patients cannot get deceased-donor liver transplants because their liver function is fairly normal in spite of their tumours. This puts them near the bottom of the national organ transplant waiting list.

Thanks to recent advances in cancer treatments, many of these patients are able to get their cancer under systemic control, which means only their liver tumours prevent them getting a ‘cancer free’ label. It also increases the odds that these patients – and their new livers – will remain cancer free, which is crucial when balancing the benefit to the patient with the risk to a living donor.

“I’ve seen so many cancer patients, whose cancers were not spreading, but we couldn’t remove the tumours from their livers and we knew they would die,” said first study author Dr Roberto Hernandez-Alejandro. “We hoped living-donor liver transplant could give them another chance.”

Because it offered a last resort, the study attracted patients from near and far. All patients and donors went through a rigorous screening process to ensure they were good candidates for the procedure, and they were educated about the risks of the surgery and the possibility of cancer recurrence.

Patients and donors underwent staggered surgeries to fully remove patients’ diseased livers and replace them with half of their donors’ livers. Over time, both patients’ and donors’ livers regenerated and regain normal function.

Patient imaging and blood analysis was closely monitored for any signs of cancer recurrence and will continue to be followed for up to five years after their surgery. At the time of study publication, two patients had follow-up of two or more years and both remained alive and well, cancer-free.

“We have seen very good outcomes with this protocol, with 100 percent survival and 62 percent of patients remaining cancer free one year and a half after surgery,” said study author Dr Mark Cattral. “It is very strong data to support that we can offer this treatment safely and make appropriate use of scarce life-saving organs.”

Source: University Health Network

Categories : TransplantsTags :

Two Pig Kidneys Transplanted into Human

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In a new study published in the American Journal of Transplantation, researchers report that they successfully transplanted two kidneys from a genetically modified pig into a human recipient who had suffered brain death.

The use of pig organs, genetically modified to enable transplantation into humans, could ease the shortage of available donor organs for transplantation and prevent thousands of deaths that result each year due to a shortage of organs. Recently, a US man became the first human recipient of a genetically modified pig heart.

This study used a novel preclinical human model to answer numerous critical safety questions. No hyperacute rejection was seen for the 74 hours until termination. No chimerism or transmission of porcine retroviruses was detected. Longitudinal biopsies revealed thrombotic microangiopathy that did not progress in severity, without evidence of cellular rejection or deposition of antibody or complement proteins. Although the xenografts produced variable amounts of urine, creatinine clearance did not recover. Whether renal recovery was impacted by the milieu of brain death and/or microvascular injury remains unknown.

The study provides important insights and identifies several areas where additional research is needed before xenotransplantation can be used to help address the current organ shortage.

“This study provides knowledge that could not be generated in animal models and moves us closer to a future where organ supply meets the tremendous need,” said senior author Jayme E. Locke, MD, MPH, of the University of Alabama at Birmingham.

Source: Wiley

Categories : TransplantsTags :

Lifestyle Changes Key for Older Kidney Transplant Recipients

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Researchers discovered that deaths among kidney transplant recipients due to factors other than organ rejection is the leading cause for transplanted kidney loss. Their findings, published in Transplantation Direct, revealed that only one in four transplanted kidney losses were caused by organ rejection.

“Immunosuppression medication to prevent rejection is often the focus when caring for patients post transplant. But this study highlights the increased risk of death from cancer and infection for transplant patients, especially those who are older and have diabetes,” said Andrew Bentall, MB, ChB, MD, the study’s co-first author.

The study involved 5752 patients who underwent a kidney transplant between 2006 and 2018. Of those, 691 died with a functioning kidney. Researchers found that 20% of these patients died from cancer; 19.7%, infection; and 12.6%, cardiac disease.

Another 553 patients lost their transplant due to the failure of a transplanted kidney. Of these patients, 38.7% of the patients’ kidneys failed due to rejection; 18.6%, glomerular diseases; and 13.9%, tubular injury.

Two types of recipients were found to be most vulnerable after transplant. The first are younger, nondiabetic patients who develop kidney failure due to organ rejection. The second group includes older, often diabetic patients who are at risk of death due to causes not associated with organ rejection, including cancer, infections and heart disease.

Care providers need to treat these two populations differently to minimise risks, according to Dr Bentall. For younger patients, that includes focusing on immunosuppression medication to prevent rejection. For older, often diabetic patients, it is critical to address chronic health issues, such as obesity, high blood pressure and diabetes. Focusing on these lifestyle changes is critical for improving long-term outcomes for kidney transplant recipients.

“It is important for these older patients that care providers emphasise the need for ongoing lifestyle changes that address obesity, high blood pressure and diabetes. Those include losing weight, exercising and new strategies for managing diabetes,” he said. “Making those changes could potentially impact the patient’s life and kidney outcomes more than immunosuppression therapies.”

Source: Mayo Clinic