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  • 151.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Perfusion of Porcine Kidneys with Macromolecular Heparin Ameliorates Early Ischemia Reperfusion InjuryArticle in journal (Refereed)
    Abstract [en]

    Background: Ischemia-reperfusion injury (IRI) is the most significant antigen-independent nonspecific insult, inevitably linked to organ transplantation. Endothelial glycocalyx is degraded during the earliest events in I/R. Previously we have been able to demonstrate the feasibility of coating the surface of the renal artery and renal tissue during hypothermic machine perfusion preservation (HMP) in a porcine model of brain death with a macromolecular heparin conjugate (CHC; Corline Systems AB, Uppsala, Sweden). The purpose of this study was to assess protective effects of coating the renal vessel walls with a heparin conjugate during hypothermic machine perfusion (HMP) against IRI and early kidney function.

    Methods: Brain death was achieved in male landrace pigs (n=6) by raising the intracranial pressure (ICP) through stepwise increasing the volume of an epidurally placed balloon to the point of exceeding the mean arterial pressure (MAP) creating a negative cerebral perfusion pressure (CPP). Both kidneys, (n = 6 in each group) were preserved for 18 h by hypothermic machine perfusion (HMP) in Lifeport® kidney transporters (Organ Recovery Systems, Chicago, IL, USA). In total 50 mg CHC was added to one of the HMP system (experimental group). An ex vivo normothermic perfusion (NP) system was developed with the purpose of evaluating kidneys function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP, with an oxygenated autologous blood using cardiopulmonary bypass machine. The haemostatic dynamics of whole blood clotting and thrombin generation was evaluated by tromboelastography.

    Results: Serum creatinine was faster reduced in the experimental group compared to the control group (P=0.023). The total urine volume after 3h of warm perfusion was larger in the experimental group (239±71 mL) compared to the control group (172±42 mL) (Ρ=0.031). Histologically tubular changes were less frequent in the experimental group (P=0.045). No difference was seen between the groups regarding tromboelastography.

    Conclusions: Perfusion of porcine kidneys with CHC during HMP ameliorates early IRI and improves organ function close after reperfusion. No increased risk of bleed was seen with this treatment. This is a protective intervention strategy that potentially may improve the outcome of kidney transplantation in a clinical setting.

  • 152.
    Sedigh, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Brännström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Magnusson, Peetra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Modifying the vessel walls in porcine kidneys during machine perfusion 2014In: Journal of Surgical Research, ISSN 0022-4804, E-ISSN 1095-8673, Vol. 191, no 2, p. 455-462Article in journal (Refereed)
    Abstract [en]

    Background: Endothelial glycocalyx regulates the endothelial function and plays an active role in maintaining vascular homeostasis. During ischemia/reperfusion, the glycocalyx is rapidly shed into the blood stream. A heparin conjugate (CHC; Corline systems AB, Uppsala, Sweden) consists of 70 heparin molecules that have the capacity to adhere strongly to biological tissues expressing heparin affinity. We hypothesized that CHC could be used to restore disrupted glycocalyx in vivo in kidneys from brain-dead pigs.

    Materials and Methods: Brain death was induced in male landrace pigs (n=6) by inflating a balloon catheter in the epidural space until obtaining negative cerebral perfusion. The recovered kidneys (n=5+5) were perfused by hypothermic machine perfusion (HMP) using two Lifeport kidney transporters (Organ Recovery Systems, Chicago, IL, USA). 50 mg CHC (including 25 mg biotinylated CHC) or 50 mg unfractionated heparin (control) was added to the perfusion fluid in the respective machines. In one case, the kidneys were used only for dose escalation of CHC with the same procedure.

    Results: CHC was detected by immunofluorescence and confocal microscopy in the inner surface of vessel walls. The binding of CHC in the kidney was confirmed indirectly by consumption of CHC from the perfusion fluid.

    Conclusions: In this first attempt, we show that CHC may be used to coat the vessel walls of perfused kidneys during HMP, an approach that could become useful in restoring endothelial glycocalyx of kidneys recovered from deceased donors to protect vascular endothelium and possibly ameliorate ischemia/reperfusion injuries.

  • 153.
    Sedigh, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nordling, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Carlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Norlin, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lubenow, Norbert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Magnusson, Peetra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Perfusion of Porcine Kidneys With Macromolecular Heparin Reduces Early Ischemia Reperfusion Injury2019In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 103, no 2, p. 420-427Article in journal (Refereed)
    Abstract [en]

    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.

  • 154.
    Sedigh, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nordling, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Norlin, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lubenow, Norbert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Magnusson, Peetra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Perfusion Of Porcine Kidneys With Macromolecular Heparin Ameliorates Early Ischemia Reperfusion Injury2015In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, p. 94-95Article in journal (Other academic)
  • 155.
    Sedigh, Amir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Initial experience with hypothermic machine perfusion of kidneys from deceased donors in the uppsala region in Sweden2013In: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 45, no 3, p. 1168-71Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Simple cold storage (CS) is the gold standard for organ preservation. Recently, evidence has been presented suggesting compared with CS hypothermic machine perfusion (HMP) improves the quality and outcome of kidneys for transplantation. Uppsala has used the LifePort Kidney Transporter to preserve deceased donor kidneys. We evaluated our first single-center 52 cases retrospectively.

    METHODS: Deceased donor kidneys preserved with HMP between July 2010 and July 2012 (n = 52) were compared with a matched historical cohort of organs preserved by CS between January 2009 and July 2012 (n = 87). We evaluated delayed graft function (DGF), creatinine level at hospital discharge, length of hospital stay, incidence of acute rejection episodes during the first year after transplantation, and graft survival.

    RESULTS: Both groups included approximately 69% expanded criteria donors (ECD). Median cold ischemia time (CIT) was 12.8 hours in the HMP group and 11.7 hours in the CS group. The incidence of DGF was 11.5% with HMP and 20.7% with CS. Compared with CS, HMP significantly reduced the occurrence of DGF from 21.4% to 0% using standard criteria kidneys (P = .046), whereas the use of HMP did not impact the occurrence of DGF with ECD kidneys. The creatinine level at hospital discharge was lower after HMP than after CS (P = .047). No difference in graft survival was observed between the groups.

    CONCLUSIONS: Machine perfusion resulted in a lower occurrence of DGF using kidneys from standard criteria donors with a lower creatinine at hospital discharge among the cohort with reasonably low CIT. Using machine perfusion seems to be safe; no adverse surgical events occurred during the study period.

  • 156.
    Sjöberg, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Assessing the Viability of Human Pancreas Grafts using 31P MR Spectroscopy - a Pilot Study2013In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 6, p. S13-S13Article in journal (Other academic)
  • 157.
    Smerud, Hilde
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Meland, Nils
    Smerud Medical Research International AS.
    Bjørneklett, Rune
    Haukeland University Hospital.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Leivestad, Torbjørn
    Oslo University Hospital, Rikshospitalet.
    Holdaas, Hallvard
    Oslo University Hospital, Rikshospitalet.
    Hartmann, Anders
    Oslo University Hospital, Rikshospitalet.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Effect of Statins on Recurrence of IgA Nephropathy and Graft Loss in Renal Transplant RecipientsManuscript (preprint) (Other academic)
  • 158.
    Stenbäck, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Johnsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Meurling, Staffan
    The Effect of Glutamine or Phospholipid Treatment on Bacterial Translocation from Defunctionalised Small BowelManuscript (Other academic)
  • 159.
    Stenbäck, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Johnsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    T-cell inhibition does not aggravate bacterial translocation from rat small bowel2006In: Transplant Immunology, ISSN 0966-3274, E-ISSN 1878-5492, Vol. 16, no 3-4, p. 208-214Article in journal (Refereed)
    Abstract [en]

    Background: T-cell mediated immunity has been proposed to have an important function in the defence against translocating microbes from the gastrointestinal tract. After small bowel transplantation massive T-cell immunosuppression is necessary to avoid rejection. As a consequence, infections with intestinal bacteria are the main contributors to mortality in this setting. This could further imply that T cells are important in limiting bacterial translocation. In a model for bacterial translocation from small bowel in the rat we examined the outcome of T-cell inactivation. Methods: The studies were performed in a model of bacterial translocation from a Thiry-Vella loop of small bowel in the rat. The animals were treated with an anti-α/β T-cell receptor monoclonal antibody (R73). Inhibition of T-cell activation was also made using the immunosuppressive drug cyclosporin A. All animals were sacrificed on day 3 postoperatively and translocation to the mesenteric lymph nodes, liver, spleen, lung and blood was evaluated. Results: Treatment with R73 resulted in an almost complete labelling of T cells but did not result in any increased bacterial translocation compared to animals treated with saline. Neither did immunosuppression with cyclosporin A. Conclusions: In the model of bacterial translocation from a defunctionalised loop of small bowel the inhibition of T cells does not increase bacterial translocation to mesenteric lymph nodes or promote the systemic spread of the translocating bacteria. This indicates that T cells do not have any important protective function against translocating microbes from defunctionalised small bowel.

  • 160.
    Stridh, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Kerjaschki, D
    Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria.
    Chen, Y
    Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rügheimer, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Åstrand, A B M
    Department of Physiology, Institute of Physiology and Pharmacology, Gothenburg University, Gothenburg, Sweden.
    Johnsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Friberg, P
    Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olerud, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Takahashi, T
    Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
    Ikegami-Kawai, M
    Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Angiotensin converting enzyme inhibition blocks interstitial hyaluronan dissipation in the neonatal rat kidney via hyaluronan synthase 2 and hyaluronidase 12011In: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 30, no 1, p. 62-69Article in journal (Refereed)
    Abstract [en]

    A functional renin-angiotensin system (RAS) is required for normal kidney development. Neonatal inhibition of the RAS in rats results in long-term pathological renal phenotype and causes hyaluronan (HA), which is involved in morphogenesis and inflammation, to accumulate. To elucidate the mechanisms, intrarenal HA content was followed during neonatal completion of nephrogenesis with or without angiotensin converting enzyme inhibition (ACEI) together with mRNA expression of hyaluronan synthases (HAS), hyaluronidases (Hyal), urinary hyaluronidase activity and cortical lymphatic vessels, which facilitate the drainage of HA from the tissue. In 6-8days old control rats cortical HA content was high and reduced by 93% on days 10-21, reaching adult low levels. Medullary HA content was high on days 6-8 and then reduced by 85% to 12-fold above cortical levels at day 21. In neonatally ACEI-treated rats the reduction in HA was abolished. Temporal expression of HAS2 corresponded with the reduction in HA content in the normal kidney. In ACEI-treated animals cortical HAS2 remained twice the expression of controls. Medullary Hyal1 increased in controls but decreased in ACEI-treated animals. Urine hyaluronidase activity decreased with time in control animals while in ACEI-treated animals it was initially 50% lower and did not change over time. Cells expressing the lymphatic endothelial mucoprotein podoplanin in ACEI-treated animals were increased 18-fold compared to controls suggesting compensation. In conclusion, the high renal HA content is rapidly reduced due to reduced HAS2 and increased Hyal1 mRNA expressions. Normal angiotensin II function is crucial for inducing these changes. Due to the extreme water-attracting and pro-inflammatory properties of HA, accumulation in the neonatally ACEI-treated kidneys may partly explain the pathological renal phenotype of the adult kidney, which include reduced urinary concentration ability and tubulointerstitial inflammation.

  • 161.
    Ståhle, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Foss, Aksel
    Gustafsson, Bengt
    Lempinen, Marko
    Lundgren, Torbjörn
    Rafael, Ehab
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Friberg, Andrew
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Clostripain, the Missing Link in the Enzyme Blend for Efficient Human Islet Isolation2015In: Transplantation Direct, ISSN 2373-8731, Vol. 1, no 5, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Background: Effective digestive enzymes are crucial for successful islet isolation. Supplemental proteases are essential as they synergize with collagenase for effective pancreas digestion. The presence of tryptic-like activity has been implicated in efficient enzyme blends and the present study aimed to evaluate if addition of clostripain, an enzyme with tryptic-like activity, could improve efficacy of the islet isolation procedure.

    Methods: Clostripain was added to the enzyme blend just before pancreas perfusion. Islets were isolated per standard method and numerous isolation parameters, islet quality control, and the number of isolations fulfilling standard transplantation criteria were evaluated. Two control organs per clostripain organ were chosen by blindly matching against body mass index, cold ischemia time, hemoglobin A1c, donor sex, and donor age.

    Results: There were no differences in pancreas weight, dissection time, digestion time, harvest time, percent digested pancreas, or total pellet volume before islet purification between control or clostripain pancreases. Glucose-stimulated insulin release results were similar between groups. Total isolation islet equivalents, purified tissue volume and islet equivalents/g pancreas as well as fulfillment of transplantation criteria favored clostripain processed pancreases.

    Conclusions: The addition of clostripain to the enzyme blend soundly improved islet yields and transplantation rates. It gently aided pancreas digestion and maintained proper islet functionality. The addition of clostripain to the enzyme blend has now been implemented into standard isolation protocols at the isolation centers in Uppsala and in Oslo.

  • 162.
    Sund, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Döhler, Bernd
    Opelz, Gerhard
    Eriksson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Clinical outcome with low-dose valacyclovir in high-risk renal transplant recipients: a 10-year experience2013In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, no 3, p. 758-765Article in journal (Refereed)
    Abstract [en]

    Background

    Cytomegalovirus (CMV) remains an important pathogen in transplant patients, and valacyclovir (VACV) prophylaxis 8 g/day has been used in high-risk CMV-seromismatched [D+/R-] renal transplant patients to decrease CMV disease. Neurotoxic adverse effects have limited its use, and the aim of the present study was to retrospectively evaluate low-dose VACV prophylaxis, 3 g/day for 90 days after transplantation, in 102 D+/R- renal transplant patients.

    Methods

    We compared patient and graft survival rates up to 5 years after transplantation with the data from the Collaborative Transplant Study Group (CTS) database. The incidence of CMV disease, rejection and neurotoxic adverse effects was analyzed up to 1 year after transplantation.

    Results

    The patient and graft survival rates up to 5 years were comparable with those derived from the CTS. CMV disease was diagnosed in 25% of the patients and 2% developed tissue-invasive CMV disease. The rejection frequency was 22% and neurotoxic adverse effects were seen in 2% of the patients.

    Conclusions

    Low-dose VACV prophylaxis (3 g/day) for 90 days post-transplantation results in high patient and graft survival rates and reduces the incidence of CMV disease. Neurotoxic adverse effects are minimal. We believe that low-dose VACV prophylaxis should be considered to form one of the arms in future prospective comparison studies for the prevention of CMV disease in the high-risk D+/R- population of renal transplant patients.

  • 163. Taube, D.
    et al.
    Jones, G.
    O'Beirne, J.
    Wennberg, L.
    Connor, A.
    Rasmussen, A.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Generic tacrolimus in solid organ transplantation2014In: Clinical Transplantation, ISSN 0902-0063, E-ISSN 1399-0012, Vol. 28, no 5, p. 623-632Article, review/survey (Refereed)
    Abstract [en]

    The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which are similar in quality, safety, and efficacy to their approved innovator drugs. There are data available for three generic brands, tacrolimus (Intas), tacrolimus (PharOS), and tacrolimus (Sandoz). Bioequivalence has been demonstrated for generic tacrolimus (Sandoz) within a narrow therapeutic range to its innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other SOT patients, including lung and heart recipients.

  • 164.
    Tedesco-Silva, Helio
    et al.
    Division of Nephrology, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil.
    Pascual, Julio
    Viklicky, Ondrej
    Basic-Jukic, Nikolina
    Cassuto, Elisabeth
    Kim, Dean Y
    Cruzado, Josep M
    Sommerer, Claudia
    Adel Bakr, Mohamed
    Garcia, Valter D
    Uyen, Huynh-Do
    Russ, Graeme
    Soo Kim, Myoung
    Kuypers, Dirk
    Buchler, Matthias
    Citterio, Franco
    Hernandez Gutierrez, Maria Pilar
    Bernhardt, Peter
    Chadban, Steve
    Department of Renal Medicine, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia.
    Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study2019In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 103, no 9, p. 1953-1963Article in journal (Refereed)
    Abstract [en]

    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.

  • 165.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    An experience of pancreas and islet transplantation in patients with end stage renal failure due to diabetes type I2009In: Current Opinion in Organ Transplantation, ISSN 1087-2418, E-ISSN 1531-7013, Vol. 14, no 1, p. 95-102Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: The aim of this article is to describe the current decision-making in an institution with availability of a programme for simultaneous pancreas-kidney transplantation and a programme for islets after kidney transplantation. This rather subjective review is supported by a background of a description of the institutional experience of these two methods. A further aim is to give the reader the message that this not a static problem but rather an evolutional/developmental process. RECENT FINDINGS: The article is based on objective numbers and encounters and mixed with personal comments. The most important observation in whole-organ pancreas transplantation is that it works very well for selected patients. The key reflection on patients undergoing islets transplantation is that the one of the things that we have not measured in objective terms is quality of life parameters. In our centre, we regret this, as we think that best subjective achievement for the patients is just that, a better quality of life. CONCLUSION: Both procedures have their advantages and drawbacks. At the moment, they do not substantially compete for organs of deceased donors. Successful islet transplantation has a much shorter history, which may allow for future developments at a more rapid scale than whole pancreas in the near future. At the moment, I consider the two procedures as supplementary rather than competitive in the treatment of diabetes type I with a need for treatment of end-stage renal failure.

  • 166.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Immunsuppressiv behandling2001In: I: Johnsson & Tufveson (red.), Transplantation, Studentlitteratur , 2001, p. 306-Chapter in book (Other academic)
  • 167.
    Tufveson, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Johnsson, Cecilia-
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Chronic allograft dysfunction - chronic rejection revisited2000In: Transplantation, Vol. 70, p. 411-Article in journal (Refereed)
  • 168.
    Tufveson, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Njurtransplantation2014In: Njurmedicin / [ed] Mattias Laurell, Ola Samuelsson, Stockholm: Liber, 2014, 4, p. 267-278Chapter in book (Other academic)
  • 169.
    Tufveson, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Transplantationsimmunologi2015In: Njursjukdom: Teori och klinik / [ed] Naomi Clyne, Bengt Rippe, Lund: Studentlitteratur AB, 2015, 1, p. 439-446Chapter in book (Other academic)
  • 170. Tydén, G.
    et al.
    Mjornstedt, L.
    Ekberg, H.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Is Rituximab Safe to Use in Kidney Transplant Patients?2010In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 10, no 8, p. 1949-1949Article in journal (Refereed)
  • 171. Tydén, G.
    et al.
    Nordén, G.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Björk, P.
    Blodgruppsinkompatibla njurar kan transplanteras2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 39, p. 1738-Article in journal (Refereed)
  • 172. Tydén, Gunnar
    et al.
    Donauer, Johannes
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Kumlien, Gunilla
    Wilpert, Jochen
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Genberg, Helena
    Pisarski, Przemislaw
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Implementation of a Protocol for ABO-incompatible kidney transplantation--a three-center experience with 60 consecutive transplantations2007In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 83, no 9, p. 1153-1155Article in journal (Refereed)
    Abstract [en]

    Background. A new protocol for ABO-incompatible kidney transplantation has recently been introduced. We report here on the joint experience of the implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany.

    Methods. The new protocol utilizes antigen-specific immunoadsorption to remove existing ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney transplantations were included in the study. The outcome is compared with the results of 274 ABO-compatible live donor transplantations performed during the same period.

    Results. Two of the ABO-incompatible grafts have been lost (non-compliance and death with functioning graft). All the remaining 58 grafts had good renal function at a follow-up of up to 61 months. We did not observe any late rebound of antibodies and there were no humoral rejections. Graft survival was 97% for the ABO-incompatible compared with 95% for the ABO-compatible. Patient survival was 98% in both groups. There was a significant variation in preoperative A/B-antibody titer between the centers, with a median 1:8 in Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative antibody adsorptions were therefore needed in Freiburg than in Stockholm and Uppsala.

    Conclusions. The new protocol was easily implemented and there were no graft losses that could be related to ABO-incompatibility. A significant inter-institutional variation in the measurement of anti-AB-antibodies was found, having a substantial impact on the number of immunoadsorptions and consequently on the total cost for the procedure. A standardized fluorescence-activated cell sorting technique for antibody quantification is much needed.

  • 173. Tydén, Gunnar
    et al.
    Ekberg, Henrik
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Mjörnstedt, Lars
    A randomized, double-blind, placebo-controlled study of single dose rituximab as induction in renal transplantation: a 3-year follow-up2012In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 94, no 3, p. e21-e22Article in journal (Refereed)
  • 174. Tydén, Gunnar
    et al.
    Genberg, Helena
    Tollemar, Jan
    Ekberg, Henrik
    Persson, Nils H.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Gäbel, Markus
    Mjörnstedt, Lars
    A randomized, doubleblind, placebo-controlled, study of single-dose rituximab as induction in renal transplantation2009In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 87, no 9, p. 1325-9Article in journal (Refereed)
    Abstract [en]

    We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. RESULTS: We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depletion of CD19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66+/-22 mL/min in the study group and 67+/-23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. CONCLUSION: We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.

  • 175. Tydén, Gunnar
    et al.
    Mjornstedt, Lars
    Ekberg, Henrik
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Authors' Reply to Letter by van den Hoogen and Hilbrands2010In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 89, no 10, p. 1295-1295Article in journal (Refereed)
  • 176.
    Von Zur-Mühlen, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wadstrom, Jonas
    Single-centre long-term follow-up of live kidney donors demonstrates preserved kidney function but the necessity of a structured lifelong follow-up2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 236-241Article in journal (Refereed)
    Abstract [en]

    Background. The increase of live kidney donation (LKD) demands that we scrutinize its long-term consequences. Socialized medicine in Sweden has allowed us to survey long-term consequences of LKD with a high response rate. Methods. Between 1974 and 2008, 455 LKDs were performed; 28 donors were deceased and 14 had moved abroad at the time of the survey. Of the remaining 413, 96% agreed to participate in a retrospective study with laboratory testing and answering a questionnaire. Results. Mean age at donation was 49 +/- 10 years, and the mean time since nephrectomy was 11 +/- 7 years (range 1-33). No death was of renal cause. S-creatinine at follow-up was 93 +/- 18 mu mol/L, 28% had treated hypertension, of whom only 52% had BP <140/90. Eleven per cent had spot microalbuminuria, and 1% were diagnosed with diabetes mellitus. Seventy-one per cent had check-ups at least every second year, but 14% had no check-ups. Eighty per cent would be willing to donate again if it were possible, and only 3% regretted the donation. Conclusion. Renal function is well preserved in the long term after donation, no case of end-stage renal disease was identified, and a large majority of our donors would donate again if it were possible. Although rates of microalbuminuria and hypertension were at expected levels, a significant number of donors demonstrated elevated blood pressure levels and inadequate antihypertensive treatment. A relatively large number of donors did not receive regular check-ups. Both of these issues demonstrate the need for a better-structured lifelong follow-up.

  • 177.
    von Zur-Mühlen, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lundgren, Torbjorn
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Karolinska, Sweden;Karolinska Univ Hosp, Dept Transplantat Surg, Karolinska, Sweden.
    Bayman, Levent
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bridges, Nancy
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Eggerman, Thomas
    NIDDK, Bethesda, MD 20892 USA.
    Foss, Aksel
    Uppsala Univ, Dept Surg Sci, Uppsala, Sweden;Natl Hosp Norway, Dept Transplantat Med, Univ Hosp Oslo, Oslo, Norway.
    Goldstein, Julia
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Jenssen, Trond
    Natl Hosp Norway, Dept Transplantat Med, Univ Hosp Oslo, Oslo, Norway.
    Jorns, Carl
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Karolinska, Sweden;Karolinska Univ Hosp, Dept Transplantat Surg, Karolinska, Sweden.
    Morrison, Yvonne
    NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
    Ryden, Mikael
    Karolinska Inst, Dept Med H7, Solna, Sweden.
    Schwieger, Traci
    Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.
    Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation2019In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 103, no 3, p. 630-637Article in journal (Refereed)
    Abstract [en]

    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.

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  • 178.
    von Zur-Mühlen, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Insulin independence after conversion from tacrolimus to cyclosporine in islet transplantation2012In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 25, no 10, p. e108-e110Article in journal (Refereed)
  • 179.
    von Zur-Mühlen, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wintzell, Viktor
    IQVIA, Solna, Sweden;Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Levine, Aaron
    IQVIA, Solna, Sweden.
    Rosenlund, Mats
    IQVIA, Solna, Sweden;Karolinska Inst, Dept Learning Informat Management & Eth, Unit Bioentrepreneurship, Solna, Sweden.
    Kilany, Suzanne
    Astellas Pharma AS, Kastrup, Denmark.
    Nordling, Sara
    Astellas Pharma AS, Kastrup, Denmark.
    Wadstrom, Jonas
    Karolinska Univ Hosp, Dept Transplantat Surg, Huddinge, Sweden.
    Healthcare Resource Use, Cost, and Sick Leave Following Kidney Transplantation in Sweden: A Population-Based, 5-Year, Retrospective Study of Outcomes: COIN2018In: Annals of Transplantation, ISSN 1425-9524, E-ISSN 2329-0358, Vol. 23, p. 852-866Article in journal (Refereed)
    Abstract [en]

    Background: Improved understanding of the impact of kidney transplantation on healthcare resource use/costs and loss of productivity could aid decision making about funding allocation and resources needed for the treatment of chronic kidney disease in stage 5.

    Material/Methods: This was a retrospective study utilizing data from Swedish national health registers of patients undergoing kidney transplantation. Primary outcomes were renal disease-related healthcare resource utilization and costs during the 5 years after transplantation. Secondary outcomes included total costs and loss of productivity. Regression analysis identified factors that influenced resource use, costs, and loss of productivity.

    Results: During the first year after transplantation, patients (N=3120) spent a mean of 25.7 days in hospital and made 21.6 outpatient visits; mean renal disease-related total cost was & euro;66,014. During the next 4 years, resource use was approximately 70% (outpatient) to 80% (inpatient) lower, and costs were 75% lower. Before transplantation, 62.8% were on long-term sick leave, compared with 47.4% 2 years later. Higher resource use and costs were associated with age <10 years, female sex, graft from a deceased donor, prior hemodialysis, receipt of a previous transplant, and presence of comorbidities. Higher levels of sick leave were associated with female sex, history of hemodialysis, and type 1 diabetes. Overall 5-year graft survival was 86.7% (95% CI 85.3-88.2%).

    Conclusions: After the first year following transplantation, resource use and related costs decreased, remaining stable for the next 4 years. Demographic and clinical factors, including age <10 years, female sex, and type 1 diabetes were associated with higher costs and resource use.

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  • 180.
    von Zur-Mühlen, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wadström, Jonas
    Department of Transplantation Surgery, Karolinska University Hospital, Huddinge, Sweden.; Hamad Med Corp, Dept Surg Transplantat, Doha, Qatar..
    Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes Over Time.2017In: Annals of Transplantation, ISSN 1425-9524, E-ISSN 2329-0358, Vol. 22, p. 773-779Article in journal (Refereed)
    Abstract [en]

    Background: We sought to study gender differences and differences over time with respect to demographics, relation to recipient,donor motives, and experiences of live kidney donation.

    Material/Methods: In all, 455 consecutive live kidney donors, representing all of the donors at our center between 1974 and 2008were considered for this study. There were 28 deceased donors and 14 donors who had moved abroad, leaving413 donors; 387 (94%) agreed to participate in this study. A questionnaire was sent and the answers wasanalyzed for gender differences and, where relevant, for changes over time.

    Results: In all sub-periods, female donors made up the majority (55–62%), except for sibling donors (45%) and childto-parent donors (40%). No significant gender differences were seen in perceived information given before donation.For males, it was more common that the recipient took the initiative to donate. For females, the motivationfor donating was more frequently to help the recipient and because others wanted them to donate.For males, it was more common to feel a moral obligation. Post-operatively, females more frequently felt sad and experienced nausea, and more frequently felt that the donation had a positive impact on their lifes. With the introduction of minimally invasive surgical techniques, donors experienced fewer problems from the operation, with no gender difference.

    Conclusions: Females donate more frequently than males, a difference that did not change over time. Only a few genderdifferences were seen in donor motives and the donation experience; however, these differences may be relevantto address the gender imbalance in kidney donations.

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  • 181. Wadstrom, J.
    et al.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, S.
    von Zur-Muhlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Single Centre Long-Term Follow-Up of Live Kidney Donors Demonstrates Preserved Kidney Function But the Necessity of a Structured Life-Long Follow-Up2014In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 98, p. 494-494Article in journal (Other academic)
  • 182. Wadstrom, J.
    et al.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, S.
    von zur-Muhlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Single Centre Long-Term Follow-Up of Live Kidney Donors Demonstrates Preserved Kidney Function But the Necessity of a Structured Life-Long Follow-Up2014In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, p. 494-494Article in journal (Other academic)
  • 183.
    Wadström, J.
    et al.
    Karolinska Univ Hosp, Dept Transplantat Surg, Huddinge, Sweden; Hamad Med Corp, Dept Surg Transplantat, Doha, Qatar.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes over Time2018In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 18, no S4: Oral Abstracts, p. 451-451Article in journal (Other academic)
  • 184.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Hand-assisted retroperitoneoscopic live donor nephrectomy: experience from the first 75 consecutive cases2005In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 80, no 8, p. 1060-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The two major life-threatening complications associated with laparoscopic live donor nephrectomy are sudden severe bleeding and intestinal injury. A combined technique-hand-assisted and retroperitoneoscopic (HARS)-reduces the risk of these life-threatening complications. In this study, we report on our experience from the first 75 consecutive HARS operations. METHODS: The data has been collected prospectively according to intention to treat and includes all consecutive donors operated with the HARS technique. Warm ischemia time, operating time, and blood loss were recorded. Complications, convalescence, and allograft outcome were followed postoperatively with a mean follow-up of 701 (range 60-1438) days. RESULTS: The mean operating time was 138 (range 85-260) minutes and the mean warm ischemia time 175 (85-510) seconds. The operative time was significantly longer in male donors. The mean bleeding was 176 (50-700) ml. There were no conversions to open surgery. Major complications comprised one pulmonary embolus and one donor required 2 units of blood transfusion. One donor was reoperated due to suspicion of trocar hernia. Nine patients experienced minor complications (fever, n=4; urinary tract infection, n=2; chylous ascites, n=1; orchialgia, n=1; subcostal pain, n=1). All except two kidneys had immediate onset of function. Neither of these could, however, be attributed to the donor operation. One recipient experienced urinary leakage and one a stenosis. Recipient and graft survival were 99% and 96%, respectively. CONCLUSIONS: We conclude that HARS facilitates the procedure by enabling short operating times and at the same time significantly reducing the risks associated with endoscopic live donor nephrectomy.

  • 185.
    Wadström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Gjertsen, Henrik
    Sugitani, Atsushi
    Fronek, Jiri
    Introducing hand-assisted retroperitoneoscopic live donor nephrectomy: Learning curves and development based on 413 consecutive cases in four centers2011In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 91, no 4, p. 462-469Article in journal (Refereed)
    Abstract [en]

    Background: Hand-assisted and retroperitoneoscopic techniques reduce the risk of bleeding and intra-abdominal complications in live donor nephrectomy (LDN). This study reports on our four-centre experience, development and learning curves from the first 413 LDN using a hand-assisted retroperitoneoscopic technique (HARS).

    Methods: The first 413 consecutive donors operated on using HARS were included in the study. Donor demographics, peri- and postoperative data, complications, and recipient outcomes have been compiled. The data was analysed as a whole and separately for each centre, looking at centre differences and learning curves over time.

    Results: Significant differences were found in donor demographics between centres for the variables: age, BMI, number of arteries, and side of operation. Mean operating time was 170.2 minutes, with significant differences between centres. Operating time was also significantly influenced by learning curves, Sex/BMI, and side of operation. Warm ischemia time differed significantly between centres and was influenced by centre-wise learning and number of arteries. Overall conversion rate was 2.4% and differed significantly between centres. There was no mortality and no intra-abdominal complications. Apart from the conversions and one pulmonary embolism, there were no major intra- or postoperative complications. Overall 3-month graft survival was 99%, with 96% immediate onset of function and 1% ureteral complications.

    Conclusions: The HARS technique reduces the risk of intra-abdominal complications. It can be implemented with excellent donor and recipient outcomes despite different population demographics and centre/surgeon-related tradition and experience. Based on our experience, we recommend the technique in order to increase the safety margin of LDN.

  • 186.
    Wadström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Laparoscopic nephropexy exposes a possible underlying pathogenic mechanism and allows successful treatment with tissue gluing of the kidney and fixation of the colon to the lateral abdominal wall2010In: International Brazilian journal of urology : official journal of the Brazilian Society of Urology, ISSN 1677-5538, Vol. 36, no 1, p. 10-17Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Surgical treatment of "Ren Mobilis" has historically been associated with poor results and fairly high morbidity. We have used a transperitoneal laparoscopic approach in order to minimize morbidity. The goal of this study was to evaluate the success rate and to discuss the possible pathogenic mechanism, which has implications for the surgical strategy. MATERIALS AND METHODS: Seven women with a right mobile kidney were examined by intravenous pyelogram and CT scans. Symptoms were judged to emanate from the mobile kidney. Transperitoneal laparoscopic nephropexy was performed. The surgical treatment consisted of fixing the kidney to the dorsal abdominal wall using tissue glue (Tisseel) after diathermy coagulation of the surfaces to induce fibrosis. The right colon was fixed with clips to the lateral abdominal wall, trapping the kidney in place. RESULTS: In 6 of the cases, there was an incomplete rotation of the ascending colon to the right side, allowing the kidney to move freely. In one case, the kidney moved into a retroperitoneal pocket of the mesocolon. The 6 cases with a lateral passage for the kidney were symptom-free at follow-up (30-80 months), but in the 7th case the patient's kidney quickly loosened and she underwent an open reoperation, after which she was symptom-free. CONCLUSION: Our series demonstrates that good results can be achieved with a transperitoneal laparoscopic approach, but also indicates that there is a common pathogenic mechanism with incomplete rotation of the ascending colon that can be corrected during surgery, which might contribute to the good results.

  • 187.
    Wadström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Martin, Amber L.
    Estok, Rhonda
    Mercaldi, Catherine J.
    Stifelman, Michael D.
    Comparison of Hand-Assisted Laparoscopy Versus Open and Laparoscopic Techniques in Urology Procedures: A Systematic Review and Meta-analysis2011In: Journal of endourology, ISSN 0892-7790, E-ISSN 1557-900X, Vol. 25, no 7, p. 1095-1104Article, review/survey (Refereed)
    Abstract [en]

    Background and Purpose: Hand-assisted laparoscopic surgery (HALS) is an integral part of the urologist's armamentarium. We aimed to perform a comprehensive meta-analysis comparing HALS renal surgery with open and laparoscopic techniques. Methods: A systematic review and meta-analysis of HALS renal procedures (donor nephrectomy, nephrectomy, or nephroureterectomy) from 1996 to 2007 was performed. Results: Sixty-two studies of 30 donor nephrectomy, 21 radical nephrectomy, and 14 nephroureterectomy procedures in 5446 patients were included in the analysis. In donor nephrectomy, estimated blood loss (EBL) was statistically significant for HALS vs the open and laparoscopic cohorts, -69.0mL (95% confidence interval [CI], -129.7, -8.2) and -40.1mL (95% CI, -68.2, -12.0), respectively. Length of stay (LOS) was shorter compared with the open group, -1.7 days (95% CI, -2.3, -1.1). For nephroureterectomy, EBL (-29.9mL (95% CI, -242.3, 182.5)), and LOS (-1.5 d [95% CI, -2.8, -0.3]) again favored HALS vs open procedures. Operating room (OR) time and warm ischemia time (WIT) were statistically significant in favor of HALS donor nephrectomy vs the laparoscopic cohort; -36.8 minutes (95% CI, -61.3, -12.3) and -1.3 minutes (95% CI, -1.8, -0.7), respectively. For radical nephrectomy, both EBL -232.9mL (95% CI, -383.6, -82.2) and LOS -2.4 days (95% CI, -3.5, -1.3) were statistically significant, favoring HALS vs the open group. Conclusion: We report the largest meta-analysis of HALS renal surgery to date. When compared with open surgery, HALS allows for a significant decrease in EBL and LOS. Compared with laparoscopic donor nephrectomy, HALS resulted in a significant decrease in blood loss, OR time, and WIT.

  • 188.
    Wadström, Jonas
    et al.
    Karolinska Univ Hosp, Dept Transplantat Surg, Huddinge, Sweden;Hamad Med Corp, Dept Surg Transplantat, Doha, Qatar.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lennerling, Annette
    Sahlgrens Univ Hosp, Transplant Inst, Gothenburg, Sweden.
    Westman, Kerstin
    Skane Univ Hosp, Dept Nephrol & Transplant, Malmo, Sweden.
    Wennberg, Lars
    Karolinska Univ Hosp, Dept Transplantat Surg, Huddinge, Sweden.
    Ekholm, Ingela Fehrman
    Karolinska Univ Hosp, Dept Transplantat Surg, Huddinge, Sweden.
    Living Anonymous Renal Donors Do Not Regret: Intermediate and Long-Term Follow-Up with a Focus on Motives and Psychosocial Outcomes2019In: Annals of Transplantation, ISSN 1425-9524, E-ISSN 2329-0358, Vol. 24, p. 234-241Article in journal (Refereed)
    Abstract [en]

    Background: Living anonymous donation (LAD) of kidneys was introduced in Sweden in 2004. This study reports on outcomes of Swedish LAD experiences from 2004 to 2016, focusing on donors' motives, the care they received, psychosocial aspects, and medical status at follow-up.

    Material/Methods: Donor data were collected through a physician interview, medical check-up, review of medical charts, the Hospital Anxiety Depression Scale (HADS), and a routine national questionnaire. Of the 26 LADs during the study period, 1 donor died and 1 declined to participate, leaving a study population of 24.

    Results: Half of the donors were male, which is a higher proportion than for directed living donors. The major motive detected was altruism. Of the 24 LADs, 96% were very satisfied and would donate again if possible, 46% noted increased self-esteem, and a third were happier after the donation. Sixty-two percent received anonymous information about the recipient and 40% would have liked to meet the recipient. HADS scores were normal. Two donors had antidepressant treatment, 1 of whom had received treatment before donation. Half mentioned that the pre-donation assessment took too long. At follow-up, mean eGFR was 62 +/- 12 mL/min/1.73 m(2), of which 16 were in CKD II and 8 were in CKD III. Four donors had developed hypertension, 1 of whom also developed type 2 diabetes.

    Conclusions: Swedish LADs are very satisfied and medical outcomes are acceptable. We propose that the transplant community and the National Board of Health and Welfare take a more active approach to informing the general public about LAD.

  • 189.
    Wadström, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Hamad Med Corp, Dept Surg Transplantat, Doha, Qatar.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Few Gender Differences in Attitudes and Experiences after Live Kidney Donation, with Minor Changes over Time2018In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 102, p. S336-S336Article in journal (Other academic)
  • 190.
    Westermark, Gunilla T.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Davalli, Alberto M.
    Secchi, Antonio
    Folli, Franco
    Kin, Tatsuya
    Toso, Christian
    Shapiro, A. M. James
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Andersson, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Further Evidence for Amyloid Deposition in Clinical Pancreatic Islet Grafts2012In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 93, no 2, p. 219-223Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The reasons for the long-term complete or partial loss of islet graft function are unknown, but there are obviously other reasons than just pure allogeneic graft rejection. Earlier studies have shown that deposition of islet amyloid polypeptide amyloid in transplanted islets may indicate a mechanism for loss of β cells.

    MATERIALS AND METHODS: Sections from liver material from four deceased islet-bearing recipients have been scrutinized for the presence of amyloid. Clinical data and certain aspects of the islet graft pathology of these patients have been published previously.

    RESULT: With this extended histological analysis, we demonstrate the occurrence of amyloid deposits in islets transplanted into the liver in three of four patients with type 1 diabetes.

    CONCLUSION: The finding adds evidence to the assumption that aggregation of islet amyloid polypeptide might be an important cause of progressing β-cell dysfunction in clinically transplanted islets.

  • 191. Wilczek, Henryk E
    et al.
    Larsson, Marie
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Ericzon, Bo-Göran
    Domino liver transplantation2008In: Journal of Hepato-Biliary-Pancreatic Surgery, ISSN 0944-1166, E-ISSN 1436-0691, Vol. 15, no 2, p. 139-148Article in journal (Refereed)
    Abstract [en]

    Orthotopic liver transplantation is today an established treatment for end stage liver diseases. However, the ongoing shortage of suitable livers together with progressively longer waiting lists prevents many patients from being transplanted, and many patients die while being on the waiting list. Using livers from living donors is one way to increase the supply of liver grafts. Another group of potential living liver donors are some selected liver recipients, whose native explanted liver in turn can be considered for transplantation into another patient. This unorthodox procedure have been named domino liver transplantation (DLT). The domino approach can be considered in patients with some genetic or biochemical disorders that today are treated by liver transplantation. The underlying rationale is that such livers ultimately cause severe systemic disease but are otherwise normal. In this review we present the current world status of DLT as well as updated results from the Domino Liver World Transplant Register (DLTR) and our own experience at the Karolinska University Hospital Huddinge with the DLT procedure.

  • 192. Winstedt, L.
    et al.
    Malmqvist, U.
    Bjorck, L.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bengtsson, M.
    Uppsala University.
    Kjellman, C.
    The IgG Specific Cysteine Protease IdeS: A Novel Candidate Drug for Pre-Transplantation Desensitization2014In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, p. 666-666Article in journal (Other academic)
  • 193. Winstedt, L.
    et al.
    Malmqvist, U.
    Bjorck, L.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bengtsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Kjellman, C.
    The IgG Specific Cysteine Protease IdeS: A Novel Candidate Drug for Pre-Transplantation Desensitization.2014In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 98, p. 666-666Article in journal (Other academic)
  • 194.
    Yamamoto, S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wilczek, H. E.
    Duraj, Frans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Groth, C-G.
    Ericzon, Bo-Göran
    Liver Transplantation with Grafts from Controlled Donors after Cardiac Death: A 20-Year Follow-up at a Single Center2010In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 10, no 3, p. 602-611Article in journal (Refereed)
    Abstract [en]

    The first liver transplantation (LTx) in Sweden was performed in 1984, but brain death as a legal death criterion was not accepted until 1988. Between November 1984 and May 1988, we performed 40 consecutive LTxs in 32 patients. Twenty-four grafts were from donors after cardiac death (DCD) and 16 grafts from heart-beating donors (HBD). Significantly, more hepatic artery thrombosis and biliary complications occurred in the DCD group (p < 0.01 and p < 0.05, respectively). Graft and patient survival did not differ between the groups. In the total group, there was a significant difference in graft survival between first-time LTx grafts and grafts used for retransplantation. There was better graft survival in nonmalignant than malignant patients, although this did not reach statistical significance. Multivariate analysis revealed cold ischemia time and post-LTx peak ALT to be independent predictive factors for graft survival in the DCD group. In the 11 livers surviving 20 years or more, follow-up biopsies were performed 18-20 years post-LTx (n = 10) and 6 years post-LTx (n = 1). Signs of chronic rejection were seen in three cases, with no difference between DCD and HBD. Our analysis with a 20-year follow-up suggests that controlled DCD liver grafts might be a feasible option to increase the donor pool.

  • 195.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    11C-hydroxyephedrine positron emission tomography imaging of pheochromocytoma: a single center experience over 11 years2012In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 7, p. 2423-2432Article in journal (Refereed)
    Abstract [en]

    CONTEXT:

    Localization of the primary tumor and detection of metastases are essential for preoperative planning and postoperative management of pheochromocytoma. When computed tomography (CT) and magnetic resonance imaging are inadequate, functional imaging adds important information in this respect.

    OBJECTIVE:

    In this study the efficacy of positron emission tomography (PET) and PET/CT with 11C-hydroxyephedrine (HED) was evaluated.

    DESIGN:

    HED-PET (n = 69) and PET/CT (n = 101) examinations of 134 patients were analyzed, of which 103 were performed before surgery and 67 postoperatively. Image findings were evaluated and tracer uptake in tumors measured as the maximum standardized uptake value (SUVmax), which was compared with histopathological and clinical data.

    RESULTS:

    Sixty HED-PET and PET/CT examinations were positive, with no false-positive and six false-negative examinations (sensitivity 91%, specificity 100%). Sensitivity of HED-PET in multiple endocrine neoplasia type II patients was lower (73%) with 100% specificity. The mean SUVmax was significantly higher when sympathetic symptoms were present and in metastases compared with primary tumors. The SUVmax correlated significantly with plasma normetanephrine and urinary norepinephrine. The mean SUVmax in HED-positive primary tumors was significantly higher than in normal adrenal glands.

    CONCLUSION:

    HED-PET and PET/CT demonstrated 91% sensitivity and maximum specificity but with lower sensitivity in multiple endocrine neoplasia type II patients. The degree of HED accumulation (SUVmax) in the tumors correlated to malignancy and biochemical data.

  • 196.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Department of surgery, Uppsala University Hospital, Uppsala, SE-75185, Sweden..
    Nelander, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ectopic pregnancy in simultaneous pancreas-kidney transplantation: A case report2016In: International journal of surgery case reports, ISSN 2210-2612, E-ISSN 2210-2612, Vol. 28, p. 152-154Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We present a case report of ectopic pregnancy (EP) after simultaneous pancreas-kidney transplantation (SKPTx). PRESENTATION OF CASE: A 33-year-old female status post SKPTx suddenly got abdominal pain in the lower level. She had high human chorionic Gonadotropin test. Ultrasonography revealed that there was no fetus in the uterus but a dilated right fallopian tube, which strongly suggested ectopic pregnancy. An emergency operation was performed and a dilated right side uterine tube was found with adhesions to her transplant. Salpingectomy was performed and no visible injury to the pancreas was found by the procedure. Pathological evaluation showed ectopic pregnant fetus, and no pancreas dysfunction was observed after the operation. DISCUSSION: This is the first case and operation report of EP after SKPTx. We should consider various causes of acute abdomen as well as several pathological condition in the transplanted pancreas such as pancreatitis, abscess, and thrombosis in vessels in the organ. Moreover, transplanted pancreas in abdomen is easily misrecognized as adipose tissue and there is high risk that the organ to get injured surgically. CONCLUSION: EP should be included in the different diagnosis in SKPTx female patients who get acute abdominal pain. It is highly desirable that transplant surgeon is included in the operation team for EP of these patients. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

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  • 197.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Univ Uppsala Hosp, Dept Surg, Div Transplantat, Uppsala, Sweden..
    Simultaneous Hand-Assisted Transperitoneal Bilateral Native Nephrectomy And Extracapsular Transplant Nephrectomy In A Patient With Polycystic Kidney Disease2015In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, p. 216-216Article in journal (Other academic)
  • 198.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wahlberg, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Biglarnia, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Factors influencing outcome of simultaneous kidney and pancreas transplantation: a 23-year single-center clinical experience2010In: Transplantation Proceedings, ISSN 0041-1345, E-ISSN 1873-2623, Vol. 42, no 10, p. 4197-4201Article in journal (Refereed)
    Abstract [en]

    Introduction:

    Simultaneous kidney and pancreas transplantation (SKPT) has become an effective treatment for patients who have diabetes mellitus type I with advanced nephropathy. This study assesses the progress of the SKPT program at Uppsala University Hospital, Sweden, and evaluates prognostic factors for graft survival.

    Materials and Methods

    Between February 1986 and September 2009, we performed 113 SKPT. The immunosuppression protocols changed over time and are defined as era 1, cyclosporine (CyA), atzathioprine (AZA) and steroids (C/A/S); era 2, C/A/S with antithymocyte globulin (ATG) induction (C/A/S/A); era 3, CyA, mycophenolate mofetic (MMF), steroids and ATG induction (C/M/S/A); era 4, tacrolimus (TAC), MMF, steroid, and ATG induction (T/M/S/A) and era 5, TAC, MMF, steroids and basiliximab induction (T/M/S/B). We analyzed donor/recipient/ operative and postoperative variables to assess their influence on pancreas graft and patient survivals.

    Results

    The overall 1-, 5-, and 10-year patient survivals were 95.5%, 84.1%, and 65.5%, respectively. The 1-, 5-, and 10-year overall pancreas graft survivals were 77.6%, 58.4%, and 48.4%. The 1-, 5-, and 10-year pancreas graft survivals in SKPT patients transplanted between October 1997 and September 2009. (T/M/S/A and T/M/S/B; eras 4 and 5) were 95.3%, 72.7%, and 63.1%, respectively, which was significantly better than those of patients transplanted between February 1986 and September 1997 (era, 1 through 3) (P < 0.01, P < 0.0001, respectively). The quadruple regimen with TAC and MMF (eras 4 and 5) decreased the incidence of acute rejection episodes compared with eras 1 through 3 (P < 0.0001). Basiliximab induction (T/M/S/B; era 5) reduced the CMV infection rate compared with eras 1 through 4 (P < 0.01). Multivariate analysis revealed that donor age (younger than 40 years), immunosuppressive regimen with TAC and MMF (eras 4 and 5), and absence of acute rejection episodes independently affected pancreas graft survival.

    Conclusions

    We demonstrate a superiority of the quadruple protocol with T/M/S/B for graft and patient survival with a decreased incidence of CMV infection after SKPT.

  • 199.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wilczek, H E
    Nowak, G
    Larsson, M
    Oksanen, A
    Iwata, T
    Gjertsen, H
    Söderdahl, G
    Wikström, L
    Ando, Y
    Suhr, O B
    Ericzon, B-G
    Liver transplantation for familial amyloidotic polyneuropathy (FAP): a single-center experience over 16 years2007In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 7, no 11, p. 2597-2604Article in journal (Refereed)
    Abstract [en]

    Orthotopic liver transplantation (LTx) is currently the only available treatment that has been proven to halt the progress of familial amyloidotic polyneuropathy (FAP). The aim of this study was to assess mortality and symptomatic response to LTx for FAP. All 86 FAP patients transplanted at our hospital between April 1990 and November 2005 were included in the study. Five patients underwent retransplantation. The 1-, 3- and 5-year patient survival rates in patients transplanted during 1996-2005 were 94.6%, 92.3% and 92.3%, respectively, a significant difference from the rates of 76.7%, 66.7% and 66.7%, respectively, during 1990-1995 (p = 0.0003). Multivariate analysis revealed that the age at the time of LTx (>or=40 years), duration of the disease (>or=7 years) and modified body mass index (mBMI) (<600) were independent prognostic factors for patient survival. A halt in the progress of symptoms was noted in most patients, but only a minority experienced an improvement after LTx. To optimize the posttransplant prognosis, LTx should be performed in the early stages of the disease, and close post-LTx monitoring of heart function by echocardiography and of heart arrhythmia by Holter ECG is mandatory.

  • 200.
    Yamamoto, Shinji
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wilczek, Henryk E
    Iwata, Takashi
    Larsson, Marie
    Gjertsen, Henrik
    Söderdahl, Gunnar
    Solders, Göran
    Ericzon, Bo-Göran
    Long-term consequences of domino liver transplantation using familial amyloidotic polyneuropathy grafts2007In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 20, no 11, p. 926-933Article in journal (Refereed)
    Abstract [en]

    Domino liver transplantation (DLT) using grafts from patients with familial amyloidotic polyneuropathy (FAP) is an established procedure at many transplantation centers. However, data evaluating the long-term outcome of DLT are limited. The aim of the present study was to analyze the risk of de novo polyneuropathy, possibly because of amyloidosis, and the patient survival after DLT. At our department, 28 DLT using FAP grafts were conducted between January 1997 and December 2005. One patient was twice subjected to DLT. Postoperative neurological monitoring of peripheral nerve function was performed with electroneurography (ENeG) in 20 cases. An ENeG index based on 12 parameters was calculated and correlated to age and/or height. Three patients developed ENeG signs of polyneuropathy 2-5 years after the DLT, but with no clinical symptoms. The 1-, 3- and 5-year actuarial patient survival in hepatocellular carcinoma (HCC) patients (n = 12) and non-HCC patients (n = 15) was 67%, 15%, 15% and 93%, 93%, 80%, respectively (P = 0.001). Development of impaired nerve conduction in a proportion of patients may indicate that de novo amyloidosis occurs earlier than previously expected. Survival after DLT was excellent except in patients with advanced HCC.

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