| 1. |
- Bergström, Marcus, et al.
(författare)
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Autologous regulatory T cells in clinical intraportal allogenic pancreatic islet transplantation
- 2021
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Ingår i: Transplant International. - : John Wiley & Sons. - 0934-0874 .- 1432-2277. ; 34:12, s. 2816-2823
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic islet transplantation in type 1 diabetes requires lifelong immunosuppression to prevent graft rejection. This medication can cause adverse effects and increases the susceptibility for infections and malignancies. Adoptive therapies with regulatory T cells (Tregs) have shown promise in reducing the need for immunosuppression in human transplantation settings but have previously not been evaluated in islet transplantation. In this study, five patients with type 1 diabetes undergoing intraportal allogeneic islet transplantation were co-infused with polyclonal autologous Tregs under a standard immunosuppressive regimen. Patients underwent leaukapheresis from which Tregs were purified by magnetic-activated cell sorting (MACS) and cryopreserved until transplantation. Dose ranges of 0.14–1.27 × 106 T cells per kilo bodyweight were transplanted. No negative effects were seen related to the Treg infusion, regardless of cell dose. Only minor complications related to the immunosuppressive drugs were reported. This first-in-man study of autologous Treg infusion in allogenic pancreatic islet transplantation shows that the treatment is safe and feasible. Based on these results, future efficacy studies will be developed under the label of advanced therapeutic medical products (ATMP), using modified or expanded Tregs with the aim of minimizing the need for chronic immunosuppressive medication in islet transplantation.
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| 2. |
- Kjellman, Christian, et al.
(författare)
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Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients
- 2021
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Ingår i: American Journal of Transplantation. - : Elsevier. - 1600-6135 .- 1600-6143. ; 21:12, s. 3907-3918
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Tidskriftsartikel (refereegranskat)abstract
- Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor-recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR-, death-censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2 , respectively. The incidence of AMR was 38% with most episodes occurring within the first month post-transplantation. Sub-analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch-positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase-enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA-incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation.
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| 3. |
- Lorant, Camilla, et al.
(författare)
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Risk Factors for Developing BK Virus-Associated Nephropathy : A Single-Center Retrospective Cohort Study of Kidney Transplant Recipients
- 2022
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Ingår i: Annals of Transplantation. - 1425-9524 .- 2329-0358. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND BK virus (BKV) infection after kidney transplantation leads to BKV-associated nephropathy (BKVAN) in up to 10% of recipients, and is associated with an increased risk of allograft dysfunction or loss. The objective of this study was to estimate the incidence of BKVAN and to analyze whether enhanced induction is associated with an increased risk of BKVAN, possibly justifying more intensive surveillance.MATERIAL AND METHODS This was a single-center retrospective cohort study. All patients who underwent kidney transplantation or simultaneous pancreas and kidney transplantation at the Uppsala University Hospital in Sweden between 2005 and 2014 were included, a period when BKV screening was not yet implemented. The effect of enhanced induction, defined as treatment with thymoglobulin, rituximab, and/or eculizumab, often in combination with IVIg and glycosorb, immunoadsorption and/or plasmapheresis/apheresis, was analyzed in a multivariable Cox proportional hazards model together with sex, age, cytomegalovirus mismatch (donor+/recipient-) and rejection treatment as co-predictors. Further, the effects of BKVAN on graft survival was analyzed in a univariable Cox proportional hazards model.RESULTS In total 44 of 928 (4.7%) patients developed a biopsy-verified BKVAN 4.8 (1.5-34.2) months after transplantation. Male sex was identified as a risk factor (HR 2.02, P=0.04) but not enhanced induction. Patients with BKVAN experienced a significantly higher risk of graft loss (HR 4.37, P<0.001).CONCLUSIONS Male sex, but not enhanced induction, was found to be a risk factor for BKVAN development after kidney transplantation. BKVAN is associated with an increased risk of graft loss.
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| 4. |
- Lorant, Camilla, et al.
(författare)
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The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia : a prospective study in kidney transplant recipients
- 2024
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Background: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-orebro region and to identify host and viral risk factors for clinically significant events.Methods This single-center prospective cohort study included kidney transplant patients aged >= 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia.Results: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)).Conclusions: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.
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| 5. |
- Pernin, Vincent, et al.
(författare)
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Long-Term Prolonged-Release Tacrolimus-Based Immunosuppression in De Novo KidneyTransplant Recipients : 5-Y Prospective Follow-Up of Patients in the ADVANCE study
- 2023
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Ingår i: Transplantation direct. - : Wolters Kluwer. - 2373-8731. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background. Although prolonged-release tacrolimus (PR-T) is widely approved for posttransplantation immunosuppres-sion in kidney recipients, large-scale studies are required to assess long-term outcomes. We present follow-up data from the ADVANCE trial, in which kidney transplant patients (KTPs) received corticosteroid minimization with PR-T.Methods. ADVANCE was a 24-wk, randomized, open-label, phase-4 study. De novo KTPs received PR-T with basiliximab and mycophe-nolate mofetil and were randomized to receive an intraoperative corticosteroid bolus plus tapered corticosteroids until day 10 (arm 1) or an intraoperative corticosteroid bolus (arm 2). In this 5-y, noninterventional follow-up, patients received maintenance immunosuppression according to standard practice. Primary endpoint included graft survival (Kaplan-Meier). Secondary end-points included patient survival, biopsy-confirmed acute rejection–free survival, and estimated glomerular filtration rate (4-vari-able modification of diet in renal disease).Results. Follow-up study included 1125 patients. Overall graft survival at 1 and 5 y posttransplant was 93.8% and 88.1%, respectively, and was similar between treatment arms. At 1 and 5 y, patient survival was 97.8% and 94.4%, respectively. Five-year graft and patient survival rates in KTPs who remained on PR-T were 91.5% and 98.2%, respectively. Cox proportional hazards analysis demonstrated similar risk of graft loss and death between treatment arms. Five-year biopsy-confirmed acute rejection–free survival was 84.1%. Mean ± standard deviation values of estimated glo-merular filtration rate were 52.7 ± 19.5 and 51.1 ± 22.4 mL/min/1.73 m2 at 1 and 5 y, respectively. Fifty adverse drug reactions were recorded, probably tacrolimus-related, in 12 patients (1.5%).Conclusions. Graft survival and patient survival—over-all and for KTPs who remained on PR-T—were numerically high and similar between treatment arms at 5 y posttransplant.
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| 6. |
- Sandvik, U., et al.
(författare)
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Does experience affect physicians’ attitude towards assisted suicide? A snapshot of Swedish doctors’ opinions
- 2022
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Ingår i: Ethics, Medicine, and Public Health. - : Elsevier. - 2352-5525 .- 2352-5533. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAssisted dying is a current and controversial topic that seems to be gaining more support among both physicians as well as the general public. This paper aims to provide a snapshot of Swedish physicians’ opinions regarding AS, including their opinion concerning experience and to evaluate whether a correlation between opinion and experience exists.Material and methodsA poll was conducted through a panel of members of the Swedish Medical Association. The panel is representative of the association's members regarding age and gender.ResultsThe response rate was 49% Of the respondents 41% stated that AS and/or euthanasia should be legalized. Doctors with great experience in working with dying patients express most strongly against AS and/or euthanasia. More than half of the respondents (54%) stated that AS if it would be legal, should be performed within specific health care units. Approximately the same proportion (48%) were willing to write a statement on health status, knowing that it would be used in decisions regarding AS. Similarly, 44% could not consider performing AS and 27% were indecisive on the question. A majority (41%) thought that a physician should be responsible for approving applications for AS.DiscussionA few more physicians express a positive attitude toward AS than against it, but many cannot express a certain opinion. In our material, no side in the “debate” for or against AS reaches the majority. The most junior physicians are the most uncertain ones.
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| 7. |
- Söfteland, John M., 1977, et al.
(författare)
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COVID-19 in solid organ transplant recipients : A national cohort study from Sweden
- 2021
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 21:8, s. 2762-2773
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Tidskriftsartikel (refereegranskat)abstract
- Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.
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