| 1. |
- Alves, Fabio de Abreu, et al.
(author)
-
Immunohistopathology of the Newly Discovered Giant Papillae Tongue Disorder in Organ-Transplanted Children
- 2017
-
In: Transplantation. - : Lippincott Williams & Wilkins. - 0041-1337 .- 1534-6080. ; 101:6, s. 1441-1448
-
Journal article (peer-reviewed)abstract
- Background. Giant papillae tongue disorder (GRID) is a newly discovered, long-lasting clinical disorder that may develop in organ-transplanted pediatric recipients. The key feature of this disorder is the unique tongue lesion, which comprises swollen fungiform papillae. The aim of this study was to characterize the immunohistopathology of this novel inflammatory condition. Methods. Six organ transplanted children with GRID were included in the study. Routine histopathology and immunohistochemical stainings for CD3, CD4, CD8, CD25, FOXP3, CD20, CD138, CD68, CD1a, CD15, CD23, and mast cell tryptase were performed. Results. Immunohistochemical analyses of the oral lesions revealed a subepithelial infiltrate that was primarily composed of CD3- and CD4-positive T cells, CD20-expressing B cells, macrophages, and CD138-positive plasma cells. The CD20-positive cells did not display the typical B cell morphology, having in general a more dendritic cell-like appearance. The CD138-expressing plasma cells were distinctly localized as a dense infiltrate beneath the accumulation of T cells and B cells. Increased numbers of CD1a-expressing Langerhans cells were detected both in the epithelium and connective tissue. Because no granulomas were observed and only single lesional eosinophils were detected, GPTD does not resemble a granulomatous or eosinophilic condition. Conclusions. We describe for the first time the immunopathological characteristics of a novel inflammatory disorder of the oral cavity, which may develop after solid organ transplantation in children.
|
|
| 2. |
|
|
| 3. |
- Berglund, David, et al.
(author)
-
Expression of Intratumoral Forkhead Box Protein 3 in Posttransplant Lymphoproliferative Disorders : Clinical Features and Survival Outcomes
- 2015
-
In: Transplantation. - : Lippincott Williams & Wilkins. - 0041-1337 .- 1534-6080. ; 99:5, s. 1036-1042
-
Journal article (peer-reviewed)abstract
- Background. The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.Methods. Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records.Results. Based on a cutoff level of 29 FoxP3+ cells per mm2, most (80%) of the PTLDs were FoxP3-. Forty-seven of 74 PTLDs displayed no FoxP3+ cells at all. The frequency of FoxP3+ cells did not influence median overall survival. The FoxP3- PTLDs were more frequently of T-cell phenotype (P=0.04), located at the graft (P=0.03), occurred earlier after transplantation (P=0.04), were more likely to develop in lung recipients (P=0.04), and in patients that had received anti T-cell globulin as induction therapy (P=0.02). The FoxP3+ PTLDs were associated with hepatitis C seropositivity (P=0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity.Conclusion. Our findings suggest that intratumoral FoxP3+ Tregs do not influence survival in patients with PTLD. FoxP3+ Tregs are rare in PTLD, possibly because of heavy immunosuppression.
|
|
| 4. |
- Berglund, Erik, et al.
(author)
-
Clinical Significance of Alloantibodies in Hand Transplantation : A Multicenter Study
- 2019
-
In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 103:10, s. 2173-2182
-
Journal article (peer-reviewed)abstract
- Background. Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. Methods. We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. Results. Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. Conclusions. While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.
|
|
| 5. |
|
|
| 6. |
- Brännström, Mats, 1958, et al.
(author)
-
Uterus transplantation: A Rapidly Expanding Field
- 2018
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 102:4, s. 569-577
-
Research review (peer-reviewed)abstract
- Uterus transplantation (UTx) has been successfully introduced as a treatment option for women with absolute uterine factor infertility (AUFI). AUFI representing approximately 3% to 5% of the female general population is linked to either congenital uterine agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome), major congenital uterine malformation (hypoplastic uterus, fraction of bicornuate/unicornuate uterus), a surgically absent uterus, or an acquired condition (intrauterine adhesions, leiomyoma) linked to uterine malfunction that causes implantation failure or defect placentation. The world's first clinical uterus transplant was performed in 2000. However, a hysterectomy became necessary shortly after the surgery due to uterine necrosis. In 2011, a group in Turkey reported on a surgically successful deceased donor transplant; however, this procedure has, to date, not resulted in a healthy live birth, the ultimate goal of UTx. Building on an extensive experimental background in various animal models, including primates, the Gothenburg group led by Brannstrom reported on the first delivery of a healthy baby in a recipient of a live donor UTx in 2014. This event did not only show the feasibility of UTx, it also helped defining relevant areas of clinical and basic research. Use of a gestational surrogate carrier, is, at least in theory, an alternative for a woman with AUFI seeking genetic motherhood. However, in the clear majority of countries worldwide, gestational surrogacy is not practiced based on legal, ethical, or religious concerns. Of note, the overwhelming majority of surveyed women in the United Kingdom, a country which permits surrogacy, preferred UTx over gestational surrogacy and adoption. Moreover, randomly selected women of fertile age in Sweden preferred UTx over gestational surrogacy. A recent large survey in Japan with more than 3000 participants revealed that UTx had a twofold higher acceptance rate compared with gestational surrogacy. In a recent US survey exploring the potential of donating vascularized composite allografts, uterus donation achieved the highest priority. Thus, the acceptance of UTx as infertility treatment for women with AUFI is high, although the procedure remains in its infancy. Here, we provide an update of clinical activities, summarize achievements and challenges, and submit areas of research interests.
|
|
| 7. |
- Drechsler, Christiane, et al.
(author)
-
Homoarginine and Clinical Outcomes in Renal Transplant Recipients : Results From the Assessment of Lescol in Renal Transplantation Study
- 2015
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 99:7, s. 1470-1476
-
Journal article (peer-reviewed)abstract
- Background: Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study.Methods: Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107).Results: Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 µmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 µmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 µmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13–5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36–4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63–10.69) and 2.50 (95% CI, 1.38–4.55), respectively.Conclusions: Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.
|
|
| 8. |
- Ericzon, Bo-Göran, et al.
(author)
-
Liver transplantation for hereditary transthyretin amyloidosis : after 20 years still the best therapeutic alternative?
- 2015
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 99:9, s. 1847-1854
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTR patients to serve as a base for comparison.METHODS: Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry.RESULTS: From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was markedly more common than that observed in patients undergoing Ltx for end-stage liver disease.CONCLUSIONS: Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in early-onset TTR Val30Met patients, requires consideration.
|
|
| 9. |
|
|
| 10. |
- Espes, Daniel, et al.
(author)
-
Cotransplantation of Polymerized Hemoglobin Reduces β-Cell Hypoxia and Improves β-Cell Function in Intramuscular Islet Grafts
- 2015
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 99:10, s. 2077-2082
-
Journal article (peer-reviewed)abstract
- Background. Muscle is a promising alternative site for islet transplantation that facilitates rapid restoration of islet vascularization. However, the development of fibrosis suggests massive cellular death after transplantation. This study tested the hypothesis that islet graft function is limited by hypoxia-related death early after intramuscular transplantation, but that this can be overcome by cotransplantation of an oxygen carrier, that is, polymerized bovine hemoglobin (PolyHb). Methods. Two hundred islets were transplanted with or without different doses of PolyHb intramuscularly to nondiabetic C57BL/6 and diabetic C57BL/6 nu/nu mice. beta-cell hypoxia and apoptosis were evaluated by immunohistochemistry after injection of the biochemical marker pimonidazole or by staining for caspase-3, respectively. Blood glucose concentrations were monitored for 30 days after islet transplantation and animals were then subjected to an intravenous glucose tolerance test. Results. Substantial hypoxia was observed in control islet grafts during the first 4 days after transplantation. Cotransplantation of PolyHb resulted in a dose-dependent reduction of beta-cell hypoxia, but beta-cell apoptosis was only reduced by cotransplantation of low-dose PolyHb (0.03 mg/g body weight) due to the inflammatory effects of higher PolyHb concentrations. Cotransplantation of low-dose PolyHb resulted in improved islet graft function 30 days after transplantation in diabetic mice, with a glucose tolerance comparable to transplantation of 50% more islets. Conclusion. We conclude that cotransplantation of islets with PolyHb can be used to effectively bridge the critical hypoxic phase immediately after transplantation, improve islet graft function, and reduce the number of islets needed for successful intramuscular transplantation.
|
|
| 11. |
- Frunza, Mihaela, et al.
(author)
-
Dealing With Public Solicitation of Organs From Living Donors-An ELPAT View
- 2015
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 99:10, s. 2210-4
-
Journal article (peer-reviewed)abstract
- Although transplant professionals have initially been reluctant to perform transplants after public solicitation of organs from living donors, nowadays these transplants are increasingly being performed and reported. After clarifying the existing terminology, we elaborate an operational definition of public solicitation that is consistent with the Ethical, Legal, and Psychosocial Aspects of Transplantation classification for living organ donation. Our aim is to critically assess this phenomenon, from a legal, moral, and practical perspective, and to offer some recommendations. From a legal point of view, we analyze the current situation in the Europe and the United States. From a moral perspective, we evaluate the various arguments used in the literature, both in favor and against. Finally, we offer a set of recommendations aimed at maximizing the organ donor pool while safeguarding the interests of potential living donors.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Gustafson, Elisabet K., et al.
(author)
-
Exposure of von Willebrand Factor on Isolated Hepatocytes Promotes Tethering of Platelets to the Cell Surface
- 2019
-
In: Transplantation. - : Wolters Kluwer. - 0041-1337 .- 1534-6080. ; 103:8, s. 1630-1638
-
Journal article (peer-reviewed)abstract
- Background. Hepatocyte transplantation (Hctx) is a potentially attractive method for the treatment of acute liver failure and liver-based metabolic disorders. Unfortunately, the procedure is hampered by the instant blood-mediated inflammatory reaction (IBMIR), a thromboinflammatory response elicited by the vascular innate immune system, causing activation of the coagulation and complement systems and clearance of transplanted cells. Observations have also revealed platelets adhered to the surface of the hepatocytes (Hc). To establish Hctx as a clinical treatment, all factors that trigger IBMIR need to be identified and controlled. This work explores the expression of von Willebrand factor (VWF) on isolated Hc resulting in tethering of platelets. Methods. VWF on Hc was studied by flow cytometry, confocal microscopy, immunoblot, and real-time polymerase chain reaction. Interaction between Hc and platelets was studied in a Chandler loop model. Adhesion of platelets to the hepatocyte surface was demonstrated by flow cytometry and confocal microscopy. Results. Isolated Hc constitutively express VWF on their cell surface and mRNA for VWF was found in the cells. Hc and platelets, independently of coagulation formed complexes, were shown by antibody blocking studies to be dependent on hepatocyte-associated VWF and platelet-bound glycoprotein Ib alpha. Conclusions. VWF on isolated Hc causes, in contact with blood, adhesion of platelets, which thereby forms an ideal surface for coagulation. This phenomenon needs to be considered in hepatocyte-based reconstitution therapy and possibly even in other settings of cell transplantation.
|
|
| 15. |
- Hellström, Vivan, et al.
(author)
-
High posttransplant cancer incidence in renal transplanted patients with pretransplant cancer
- 2017
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 101:6, s. 1295-1302
-
Journal article (peer-reviewed)abstract
- Background. Patients with previous cancer have increasingly been accepted for renal transplantation. Posttransplant cancer risk and survival rates of these patients are unknown. Our objective was to assess the risk of posttransplant cancer in this patient group. Methods. In this retrospective, nested case-control study, we assessed the outcome of all (n = 95) renal transplanted patients with pretransplant cancer diagnoses in the Uppsala-Orebro region, Sweden. The control group was obtained from the Collaborative Transplant Study registry and included European patients without pretransplant cancer. The other control group comprised the entire renal transplanted population in Uppsala. Development of recurrent cancer, de novo cancer, and patient survival were determined. Results. Patients with pretransplant cancer showed higher incidence of posttransplant cancers and shorter survival compared with the control groups (P < 0.001). No obvious pattern in malignant diagnoses was observed. Death-censored graft survival was unaffected. Conclusions. Despite previously adequate cancer treatments and favorable prognoses, almost half of the patients experienced a posttransplant cancer. These observations do not justify abstaining from transplanting all patients with previous malignancies, because more than 50% of the patients survive 10 years posttransplantation. A careful oncological surveillance pretransplant as well as posttransplant is recommended.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Kisch, Annika M., et al.
(author)
-
The Meaning of Being a Living Kidney, Liver or Stem Cell Donor : A Meta-Ethnography
- 2018
-
In: Transplantation. - : Wolters Kluwer. - 0041-1337 .- 1534-6080. ; 102:5, s. 744-756
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Studies on living donors from the donors' perspective show that the donation process involves both positive and negative feelings involving vulnerability. Qualitative studies of living kidney, liver, and allogeneic hematopoietic stem cell donors have not previously been merged in the same analysis. Therefore, our aim was to synthesize current knowledge of these donors' experiences in order to deepen understanding of the meaning of being a living donor for the purpose of saving or extending someone's life.METHODS: The meta-ethnography steps presented by Noblit & Hare in 1988 were used.RESULTS: Forty-one qualitative studies from 1968 to 2016 that fulfilled the inclusion criteria were analyzed. The studies comprised experiences of over 670 donors. The time since donation varied from 2 days to 29 years. A majority of the studies, 25 out of 41, were on living kidney donors. The synthesis revealed that the essential meaning of being a donor is doing what one feels one has to do, involving 6 themes; A sense of responsibility, Loneliness and abandonment, Suffering, Pride and gratitude, A sense of togetherness, and A life changing event.CONCLUSION: The main issue is that one donates irrespective of what one donates. The relationship to the recipient determines the motives for donation. The deeper insight into the donors' experiences provides implications for their psychological care.
|
|
| 19. |
- Kisch, Annika M., et al.
(author)
-
The Meaning of Being a Living Kidney, Liver, or Stem Cell Donor—A Meta-Ethnography
- 2018
-
In: Transplantation. - : Wolters Kluwer. - 0041-1337 .- 1534-6080. ; 102:5, s. 744-756
-
Research review (peer-reviewed)abstract
- Background: Studies on living donors from the donors’ perspective show that the donation process involves both positive and negative feelings involving vulnerability. Qualitative studies of living kidney, liver, and allogeneic hematopoietic stem cell donors have not previously been merged in the same analysis. Therefore, our aim was to synthesize current knowledge of these donors’ experiences to deepen understanding of the meaning of being a living donor for the purpose of saving or extending someone's life.Methods: The meta-ethnography steps presented by Noblit and Hare in 1988 were used.Results: Forty-one qualitative studies from 1968 to 2016 that fulfilled the inclusion criteria were analyzed. The studies comprised experiences of over 670 donors. The time since donation varied from 2 days to 29 years. A majority of the studies, 25 of 41, were on living kidney donors. The synthesis revealed that the essential meaning of being a donor is doing what one feels one has to do, involving 6 themes; A sense of responsibility, loneliness and abandonment, suffering, pride and gratitude, a sense of togetherness, and a life changing event.Conclusions: The main issue is that one donates irrespective of what one donates. The relationship to the recipient determines the motives for donation. The deeper insight into the donors’ experiences provides implications for their psychological care.
|
|
| 20. |
- Korsgren, Erik, et al.
(author)
-
Glucose Effectiveness : The Mouse Trap in the Development of Novel beta-Cell Replacement Therapies
- 2016
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 100:1, s. 111-115
-
Journal article (peer-reviewed)abstract
- Background Cure of diabetes and normalization of glucose disposal during intravenous glucose tolerance tests (IVGTT) remains critical for stringent evaluation of novel replacement therapies in type 1 diabetes. Glucose disposal during an IVGTT depends on a complex interaction of both insulin-dependent and -independent mechanisms. Glucose effectiveness, that is, the function of glucose per se, independent of insulin, to stimulate its uptake and suppress endogenous glucose production is less recognized. Methods To unravel the relative importance of these pathways, rats were injected with streptozotocin to induce diabetes and implanted subcutaneously with slow-release devices of insulin. Results These animals demonstrated rapid normalization of blood glucose and perfectly normal glucose disposal during an IVGTT with no differences when compared with nondiabetic controls even though no active c-peptide secretion was detected in plasma and almost no remaining insulin-producing cells were present in the pancreas. Conclusions The present study highlights that glucose is the predominant mediator of its own disposal in rodents having only basal and nonglucose-regulated plasma insulin levels. The herein presented results calls for a reassessment how results obtained in the most commonly used experimental models should be interpreted in the development of future replacement therapies in type 1 diabetes.
|
|
| 21. |
- Markmann, James F., et al.
(author)
-
Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of beta-Cell Replacement
- 2016
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 100:7, s. E25-E31
-
Research review (peer-reviewed)abstract
- The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
|
|
| 22. |
|
|
| 23. |
- Olsson, Richard F., et al.
(author)
-
Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency : The Karolinska Experience
- 2016
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 100:6, s. 1356-1362
-
Journal article (peer-reviewed)abstract
- Background. Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder. Methods. We have so far treated 5 patients with C1q deficiency. In 3 cases, SLE symptoms remained relatively mild after the start of medical therapy, but 2 patients developed treatment-resistant SLE, and we decided to pursue treatment with allo-HSCT. For this purpose, we chose a conditioning regimen composed of treosulfan (14 g/m(2)) and fludarabine (30 mg/m(2)) started on day -6 and given for 3 and 5 consecutive days, respectively. Thymoglobulin was given at a cumulative dose of 8 mg/ kg, and graft-versus-host disease prophylaxis was composed of cyclosporine and methotrexate. Results. A 9-year-old boy and a 12-year-old girl with refractory SLE restored C1q production after allo-HSCT. This resulted in normal functional properties of the classical complement pathway followed by reduced severity of SLE symptoms. The boy developed posttransplant lymphoproliferative disease, which resolved after treatment with rituximab and donor lymphocyte infusion. Unfortunately, donor lymphocyte infusion induced severe cortisone-resistant gastrointestinal graft-versus-host disease, and the patient died from multiple organ failure 4 months after transplantation. The girl is doing well 33 months after transplantation, and clinically, all signs of SLE have resolved. Conclusions. Allo-HSCT can cure SLE in human C1q deficiency and should be considered early in subjects resistant to medical therapy.
|
|
| 24. |
- Pihlstrom, Hege, et al.
(author)
-
Increased Risk of All-Cause Mortality and Renal Graft Loss in Stable Renal Transplant Recipients With Hyperparathyroidism
- 2015
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 99:2, s. 351-359
-
Journal article (peer-reviewed)abstract
- Background. Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study. Methods. We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years. Results. Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P = 0.004), and with graft loss (6% increased risk per 10 units; P < 0.001), but not with major cardiovascular events. Parathyroid hormone above the upper limit of normal (65 pg/mL) indicated a 46% (P = 0.006) higher risk of death and an 85% higher risk of graft loss (P < 0.001) compared with low/normal values. Conclusions. Hyperparathyroidismis an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.
|
|
| 25. |
- Pippias, Maria, et al.
(author)
-
Long-term Kidney Transplant Outcomes in Primary Glomerulonephritis: Analysis From the ERA-EDTA Registry
- 2016
-
In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 100:9, s. 1955-1962
-
Journal article (peer-reviewed)abstract
- Background We evaluated the 15-year kidney allograft survival in patients with primary glomerulonephritis and determined if the risk of graft loss varied with donor source within each glomerulonephritis group. Methods Using data from the European Renal Association-European Dialysis and Transplant Association Registry, Kaplan-Meier, competing risk, and Cox regression analyses were performed on adult, first kidney transplant recipients during 1991 to 2010 (n = 14 383). Follow-up was set to December 31, 2011. Adjustments for pretransplant dialysis duration, sex, country, and transplant era were made. Death-adjusted graft survival was assessed in patients with glomerulonephritis and compared with those with autosomal dominant polycystic kidney disease (ADPKD), in which the native kidney disease cannot recur. Additionally, death-adjusted graft survival was compared between living and deceased donor transplants within each glomerulonephritis group. Results All glomerulonephritides had a 15-year death-adjusted graft survival probability above 55%. The 15-year risk of death-adjusted graft failure compared to ADPKD ranged from 1.17 (95% confidence interval [95% CI], 1.05-1.31) for immunoglobulin A nephropathy to 2.09 (95% CI, 1.56-2.78) for membranoproliferative glomerulonephritis type II. The expected survival benefits of living over deceased donor transplants were not present in membranoproliferative glomerulonephritis type I (adjusted hazard ratios [HRa], 1.08; 95% CI, 0.73-1.60) or type II (HRa, 0.90; 95% CI, 0.32-2.52) but present in immunoglobulin A nephropathy (HRa, 0.74; 95% CI, 0.59-0.92), membranous nephropathy (HRa, 0.47; 95% CI, 0.29-0.75), and focal segmental glomerulosclerosis (HRa, 0.69; 95% CI, 0.45-1.06). Conclusions This large European study shows favorable long-term kidney graft survival in all primary glomerulonephritides, although this remains lower than graft survival in ADPKD, and confirms that the reluctance to use living donors in some primary glomerulonephritides remains unfounded. These data will further inform prospective renal transplant recipients and donors during pretransplant counselling.
|
|
| 26. |
- Ringden, Olle, et al.
(author)
-
The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Inherited Diseases Is Influenced by HLA Match, Year of Transplantation, and Immunized Female Donor
- 2019
-
In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 103:6, s. 1247-1252
-
Journal article (peer-reviewed)abstract
- Background For many inborn errors of metabolism (IEM), allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure.Methods We report the outcome in 160 patients with inherited diseases, who were treated with HSCT in 3 decades. Median age was 3 years (range 0.1-63). Grafts were from matched related donors (MRDs, 56), matched unrelated donors (MUDs, 66), or HLA-mismatched donors (38).Results Graft failure (GF) occurred in 26 patients (16%), severe acute graft-versus-host disease (GVHD) in 9 (6%), and chronic GVHD in 23 (12%). Ten-year survival was 64% before the year 2000 and 86% after that (P = 0.01). Ten-year survival for MRD grafts was 90%, as opposed to 79% for MUD grafts and 56% for HLA-mismatched grafts (P = 0.03). In multivariate analysis, GF was associated with having an HLA-mismatched donor (P < 0.05) or MUD (P = 0.015) and with reduced-intensity conditioning (P < 0.01). Death was associated with year of transplant (P = 0.015), having an HLA-mismatched donor (P < 0.001), and being a male recipient from an immune female donor (P = 0.05).Conclusions The outcome after HSCT for IEM depends on HLA match, year and immune female donor.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Sedigh, Amir, et al.
(author)
-
Perfusion of Porcine Kidneys With Macromolecular Heparin Reduces Early Ischemia Reperfusion Injury
- 2019
-
In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 103:2, s. 420-427
-
Journal article (peer-reviewed)abstract
- Background: Previously, we have been able to demonstrate the possibility of coating the inner surface of the renal arteries in porcine kidneys with a heparin conjugate during hypothermic machine perfusion (HMP). The purpose of this study was to assess the efficacy of this treatment in reducing early ischemia-reperfusion injury.Method: Brain death was induced in male landrace pigs by stepwise volume expansion of an epidural balloon catheter until negative cerebral perfusion pressure (CPP) was obtained. Both kidneys (matched pairs; n = 6 + 6) were preserved for 20 hours byHMP during which 50mg heparin conjugate was added to one of the HMP systems (treated group). A customized ex vivo normothermic oxygenated perfusion (NP) system with added exogenous creatinine was used to evaluate early kidney function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP.Results: Kidney weight was lower at the end of NP (P = 0.017) in the treated group compared with control kidneys. The rate of decline in creatinine level was faster (P = 0.024), total urinary volume was higher (P = 0.031), and the level of urine neutrophil gelatinase-associated lipocalin (NGAL) was lower (P = 0.031) in the treated group. Histologically, less tubular changes were seen (P = 0.046). During NP intrarenal resistance remained lower (P < 0.0001) in the treated group.Conclusions: Perfusion of porcine kidneys with heparin conjugate during HMP reduces preservation injury and improves organ function shortly after reperfusion. No increased risk of bleeding was seen in this setup. This protective strategy may potentially improve the quality of transplanted kidneys in the clinical setting.
|
|
| 30. |
- Suhr, Ole B, et al.
(author)
-
Survival After Transplantation in Patients With Mutations Other Than Val30Met : Extracts From the FAP World Transplant Registry
- 2016
-
In: Transplantation. - : Lippincott Williams & Wilkins. - 0041-1337 .- 1534-6080. ; 100:2, s. 373-381
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Liver transplantation (LTx) has been performed for hereditary transthyretin amyloidosis (ATTR) since 1990. Outcomes for a relatively large series of LTx ATTR patients with the Val30Met (mutation are available, but for non-Val30Met patients, only a few reports with a small number of patients exist. Here, we present outcomes for non-Val30Met ATTR patients after LTx, as reported to the Familial Amyloid Polyneuropathy World Transplant Registry (FAPWTR).METHODS: Data regarding outcome were extracted for all non-Val30Met patients reported to the registry. Survival rates were analyzed by the Kaplan-Meier method and log-rank test.RESULTS: The total number of patients with a non-Val30Met mutation in the registry was 264 (174 men and 90 women), representing 57 mutations. The 10-year survival varied markedly for the 9 most common mutations, ranging from 21% for Ser50Arg to 85% for Val71Ala. Poor survival was noted for all mutations with leptomeningeal complications except for those with the Tyr114Cys mutation.CONCLUSIONS: Large differences in survival were observed relative to different mutations and between mutations with similar phenotypes. Excellent survival was noted for mutations, such as Leu111Met, Val71Ala, and Leu58His. Patients with mutations other than Val30Met are not a homogeneous group, and the term non-Val30Met should be used with caution or avoided. Moreover, for several mutations, data are too limited to allow evaluation of the efficacy of LTx, and continuous international collaboration is important for obtaining treatment guidance.
|
|
| 31. |
- Tedesco-Silva, Helio, et al.
(author)
-
Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants : An Analysis From the Randomized TRANSFORM Study
- 2019
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 103:9, s. 1953-1963
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail.METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids.RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA.CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.
|
|
| 32. |
- Thorsen, Trygve, et al.
(author)
-
Transplantation With Livers From Deceased Donors Older Than 75 Years
- 2015
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 99:12, s. 2534-2542
-
Journal article (peer-reviewed)abstract
- Background. The availability of donor organs limits the number of patients in need who are offered liver transplantation. Measures to expand the donor pool are crucial to prevent on-list mortality. The aim of this study was to evaluate the use of livers from deceased donors who were older than 75 years. Methods. Fifty-four patients who received a first liver transplant (D75 group) from 2001 to 2011 were included. Donor and recipient data were collected from the Nordic Liver Transplant Registry and medical records. The outcome was compared with a control group of 54 patients who received a liver graft from donors aged 20 to 49 years (D20-49 group). Median donor age was 77 years (range, 75-86 years) in the D75 group and 41 years (range, 20-49 years) in the D20-49 group. Median recipient age was 59 years (range, 31-73 years) in the D75 group and 58 years (range, 31-74 years) in the D20-49 group. Results. The 1-, 3-, and 5-year patient/graft survival values were 87/87%, 81/81%, and 71/67% for the D75 group and 88/87%, 75/73%, and 75/73% for the D20-49 group, respectively. Patient (P = 0.89) and graft (P = 0.79) survival did not differ between groups. The frequency of biliary complications was higher in the D75 group (29.6/13%, P = 0.03). Conclusions. Selected livers from donors over age 75 years should not be excluded based on age, which does not compromise patient or graft survival despite a higher frequency of biliary complications.
|
|
| 33. |
|
|
| 34. |
- Van Assche, Kristof, et al.
(author)
-
The Relevance of Directive 2010/53/EU for Living Organ Donation Practice: An ELPAT View
- 2015
-
In: Transplantation. - 0041-1337 .- 1534-6080. ; 99:10, s. 2215-22
-
Journal article (peer-reviewed)abstract
- With the recent transposition of Directive 2010/53/EU into the transplant regulation of EU Member States, the time is right to have a closer look at its implications for living organ donation practice. We first discuss the relevance of the Action Plan which forms the basis for the policy of the European Commission in the field of organ donation and transplantation. We then analyze the impact of Directive 2010/53/EU which was adopted to support the implementation of the Priority Actions set out in the Action Plan. We more specifically focus on the obligations of transplant centers engaged in living organ donation and highlight their significance for clinical practice. Finally, we point out some strengths and weaknesses of the Directive in addressing living organ donation.
|
|
| 35. |
- von Zur-Mühlen, Bengt, Docent, 1966-, et al.
(author)
-
Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation
- 2019
-
In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 103:3, s. 630-637
-
Journal article (peer-reviewed)abstract
- Background. When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR. Methods. The Clinical Islet Transplantation consortium 01 study was a phase II, multicenter, open label, active control, randomized study. Twenty-four subjects were randomized to peritransplant intraportal and systemic treatment with either LMW-DS or heparin, targeting an activated partial thromboplastin time of 150 +/- 10 seconds and 50 +/- 5 seconds, respectively. C-peptide response was measured with a mixed meal tolerance test at 75 and 365 days after transplant. Results. Low molecular dextran sulfate was safe and well tolerated with similar observed adverse events (mostly attributed to immunosuppression) as in the heparin arm. There was no difference in the primary endpoint (stimulated C-peptide 75 +/- 5 days after the first transplant) between the 2 arms (1.33 +/- 1.10 versus 1.56 +/- 1.36 ng/mL, P = 0.66). Insulin requirement, metabolic parameters, Clarke and HYPO score, quality of life, and safety were similar between the 2 treatments groups. Conclusions. Even with low dosing, LMW-DS showed similar efficacy in preventing IBMIR to promote islet engraftment when compared to "state-of-the art" treatment with heparin. Furthermore, no substantial differences in the efficacy and safety endpoints were detected, providing important information for future studies with more optimal dosing of LMW-DS for the prevention of IBMIR in islet transplantation.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Wange, Niklas, et al.
(author)
-
Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients
- 2018
-
In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 102:2, s. e59-e66
-
Journal article (peer-reviewed)abstract
- Background. Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesized mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients. Methods. The medical records of all LTx ATTRm amyloidosis patients in the county of Vasterbotten, Sweden, were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status. Results. Sixty-three patients that had survived for 3 years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P < 0.002). AC therapy significantly reduced CVEs, including bleeding in patients with AF (P = 0.04). Multivariate analysis identified AF as the only remaining regressor with a significant impact on CVE (hazard ratio, 3.8; 95% confidence interval 1.1-9.5; P = 0.029). Conclusions. AF is an important risk factor for CVE in LTx ATTRm amyloidosis patients, and AC therapy should be considered. However, the increased bleeding risk with AC therapy in patients with intracranial amyloidosis should be acknowledged.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Auråen, Henrik, et al.
(author)
-
Effect of Donor Age on Outcome of Lung Transplantation Stratified by Recipient Diagnosis : A Nordic Multicenter Study
- 2019
-
In: Transplantation. - 1534-6080. ; 103:4, s. 807-814
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Organs from older donors are increasingly used in lung transplantation, and studies have demonstrated that this could be safe in selected recipients. However, which recipient groups that have the largest benefit of older organs are unclear. This multicenter study reviews all bilateral lung transplantations (BLTx) from donors 55 years or older stratified by recipient diagnosis and compares outcomes with transplantations from younger donors. METHODS: All BLTx recipients (excluding retransplantation) at 5 Scandiatransplant centers between 2000 and 2013 were included (n = 913). Recipients were stratified to diagnosis groups including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and "other." Intensive care unit (ICU) length of stay (LOS) and survival were assessed. RESULTS: Overall, there was no difference in survival among patients transplanted from donors 55 years or older compared with younger donors. However, in CF recipients, donor age 55 years or older was associated with inferior survival (P = 0.014), and this remained significant in a multivariate model (hazard ratio, 5.0; 95% confidence interval, 1.8-14.1; P = 0.002). There was no significant effect of donor age on survival in recipients with COPD, ILD, or in the "other" group in multivariate models. Utilization of older donors was associated with increased ICU LOS for recipients with CF and ILD, but not in the COPD or "other" group. CONCLUSIONS: The BLTx recipients with CF had inferior survival and longer ICU LOS when receiving organs from donors 55 years or older. Recipients with COPD, ILD, or in the "other" group did not have inferior survival in multivariate models.
|
|
| 43. |
- Biró, Péter, et al.
(author)
-
Building Kindey Exchange Programmes in Europe - An Overview of Exchange Practice and Activities
- 2019
-
In: Transplantation. - 1534-6080. ; 103:7, s. 1514-1522
-
Journal article (peer-reviewed)abstract
- Bakgrund: Considerable differences exist among the living donor Kidney Exchange Programmes (KEPs) that are in use and being built in Europe, contributing to a variation in the number of living donor transplants [6]. Efforts of European KEPs to exchange (best) practices and share approaches to address challenges have, however, been limited.Methods: Experts from 23 European countries, collaborating on the ENCKEP COST Action, developed a questionnaire to collect detailed information on the functioning of all existing KEPs in Europe, as well as their opportunities and challenges. Following a comparative analysis, results were synthesised and interpreted by the same experts.Results: The practices, opportunities and challenges reported by 17 European countries reveal that some of the 10 operating programmes are mature, while others are in earlier stages of development. Over 1300 transplants were performed through existing KEPs up to the end of 2016, providing approximately 8% of their countries’ living kidney donations in 2015. All countries report challenges to either initiating KEPs or increasing volumes. Some challenges are shared, whilst others differ because of differences in context (eg, country size, effectiveness of deceased donor programme) and ethical and legal considerations (eg, regarding living donation as such, nonrelated donors, and altruistic donation). Transnational initiatives have started in Central Europe, Scandinavia, and Southern Europe.Conclusions: Exchange of best practices and shared advancement of national programmes to address existing challenges, aided by transnational exchanges, may substantially improve access to the most (cost) effective treatment for the increasing number of patients suffering from kidney disease.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
