| 1. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation : A Clinical Perspective
- 2015
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Ingår i: IMMUNE RESPONSES TO BIOSURFACES. - Cham : Springer International Publishing. - 9783319186030 - 9783319186023 ; , s. 211-233
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Konferensbidrag (refereegranskat)abstract
- The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term "sensitization" applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to "matched" organs from the both living and deceased donor pool. Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.
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| 2. |
- Weinreich, Ilse Duus, et al.
(författare)
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Scandiatransplant Exchange Program (STEP) : Development and Results From an International Kidney Exchange Program
- 2023
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Ingår i: Transplantation direct. - : Lippincott Williams & Wilkins. - 2373-8731. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Background. Kidney transplant candidates may be incompatible with their intended living donors because of the presence of antibodies against HLA and/or ABO. To increase the possibility of finding an acceptable kidney donor for these patients, the Scandiatransplant Exchange Program (STEP) program within Scandiatransplant was launched in 2019.Methods. This is a retrospective review of our experiences from the first 4 y of the STEP program, including details about the match runs, performed transplantations, and recipient outcomes within the program.Results. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in >= 3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility. Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023.Results. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in >= 3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility. Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023.Conclusions. The STEP program offers sensitized patients an enlarged pool of living donors and a chance of a compatible international living donor, resulting in an increased number of total transplantations. Currently, STEP is one of the largest transnational kidney exchange programs and has improved the situation for patients waiting for kidney transplantation in Scandiatransplant.
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| 3. |
- Al Ahmadi, Ibrahim, et al.
(författare)
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Initial Experience From Implementation of Hand-Assisted Retroperitoneoscopic Live Donor Nephrectomy in Saudi Arabia
- 2013
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Ingår i: Annals of Saudi Medicine. - 0256-4947 .- 0975-4466. ; 33:2, s. S58-S59
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Donor risks and morbidity are consequences of the invasiveness of donor nephrectomy procedure. The flank incision is currently the default donor nephrectomy procedure at the King Faisal Hospital in Saudi Arabia. In order to minimize the surgical-related trauma, we are implementing the hand-assisted retroperitoneoscopic live donor nephrectomy (HARS), which previously has been shown to promote donor safety. Here, we present our initial experience with this procedure. Material and Methods: The HARS technique was implemented at our center in 2010. We present a survey of our data regarding operative characteristics as well as donor/recipient outcome. Given the small number of cases, data are presented as median with range. Results: Between 2010 and 2013, 18 left -sided HARS nephrectomy procedures were performed. The median donor age and BMI were 26.5 (18-43) and 24.1 (18.7-30.7), respectively. The median hospitalization was 4 days (3-5). One donor presented wound seroma in the pfannenstiell incision with no need for intervention. Another donor presented unspecific thoracoabdominal pain on postoperative day 2. No intra-and postoperative bleeding was observed. The median creatinine at the current follow-up was 90 mu mol/L with 100% graft survival. Conclusion: HARS is a feasible and safe technique. However, for implementation of HARS as the default donor nephrectomy procedure more practice is needed.
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| 4. |
- Baba, Hideo A., et al.
(författare)
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Survivin is upregulated during liver regeneration in rats and humans and is associated with hepatocyte proliferation
- 2009
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Ingår i: Liver international. - : Wiley. - 1478-3223 .- 1478-3231. ; 29:4, s. 585-592
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Survivin regulates cell division and inhibits apoptosis. Liver regeneration is a complex process involving both proliferation and apoptosis. The role of survivin is not well elucidated and no data exist in humans.METHODS: Seventy per cent liver resection was used to investigate liver regeneration in rats. Survivin was identified by means of reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemistry. Proliferation and apoptosis were quantified. Liver biopsies from 33 patients who underwent living donor liver transplantation were used to study survivin immuno-expression, proliferation and apoptosis within the first 17 days after transplantation. Seven healthy donors served as controls.RESULTS:Survivin transcript and protein were significantly upregulated in rat hepatocytes after 24-72 h during regeneration and showed a significant correlation with proliferation but not with apoptosis. In humans, survivin was nearly absent in donor and reperfused liver tissue but increased significantly 5-7 days after transplantation and correlated with proliferation but not with apoptosis.CONCLUSIONS: Survivin is upregulated in human and rodent liver regeneration and correlates with proliferation, suggesting an association of survivin and cell division.
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| 5. |
- Berglund, David, et al.
(författare)
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Obtaining regulatory T cells from uraemic patients awaiting kidney transplantation for use in clinical trials
- 2013
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 173:2, s. 310-322
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Tidskriftsartikel (refereegranskat)abstract
- Adoptive transfer of regulatory T cells (Tregs) has been proposed for use as a cellular therapy to induce transplantation tolerance. Preclinical data are encouraging, and clinical trials with Treg therapy are anticipated. In this study, we investigate different strategies for the isolation and expansion of CD4+CD25highCD127low Tregs from uraemic patients. We use allogeneic dendritic cells (DCs) as feeder cells for the expansion and compare Treg preparations isolated by either fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS) that have been expanded subsequently with either mature or tolerogenic DCs. Expanded Treg preparations have been characterized by their purity, cytokine production and in-vitro suppressive ability. The results show that Treg preparations can be isolated from uraemic patients by both FACS and MACS. Also, the type of feeder cells used in the expansion affects both the purity and the functional properties of the Treg preparations. In particular, FACS-sorted Treg preparations expanded with mature DCs secrete more interleukin (IL)-10 and granzyme B than FACS-sorted Treg preparations expanded with tolerogenic DCs. This is a direct comparison between different isolation techniques and expansion protocols with Tregs from uraemic patients that may guide future efforts to produce clinical-grade Tregs for use in kidney transplantation.
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| 6. |
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| 7. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Desensitization With Antigen-Specific Immunoadsorption Interferes With Complement in ABO-Incompatible Kidney Transplantation
- 2012
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 93:1, s. 87-92
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Complement activation was characterized during and after desensitization treatment in 19 consecutive patients receiving ABO-incompatible (ABOi) living donor kidney transplants to assess the effect of desensitization protocol including antigen-specific immunoadsorption (IA) on complement activation.METHODS:All patients received rituximab- and tacrolimus-based triple treatment. Anti-A/B antibodies were removed by IA. Serial determinations of C3, C3a, the C3a/C3 ratio, and sC5b-9 were carried out between day -30 and postoperative day 30. C1q was measured on day -30 and the day before the transplantation. In two recipients, eluates from immunoadsorbent columns were analyzed for C3a, C1q, and immunoglobulins by western blotting. Same complement analysis was performed in eluate from a control column after in vitro perfusion of AB-plasma.RESULTS:Patient and graft survival were 100% for a median follow-up of 40 months (range, 12-60 months). There were no humoral rejections based on ABO-antigen-antibody interactions. C3a and the C3a/C3 ratio declined with the start of IA treatment, and this decline was maintained postoperatively. C1q declined from day -30 to a lower value on the day before transplantation (P<0.05). In eluates from both patient and control, immunoadsorbent column immunoglobulins together with C3a and C1q were detected.CONCLUSIONS:The current protocol including antigen-specific IA interferes with the complement system; this effect may be partially responsible for the absence of humoral rejection resulting from ABO-antigen-antibody interactions and the excellent outcomes obtained after ABO-incompatible kidney transplantation.
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| 8. |
- Biglarnia, Ali-Reza, 1973-, et al.
(författare)
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Efficacy and safety of continuous local infusion of ropivacaine after retroperitoneoscopic live donor nephrectomy
- 2011
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:1, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- Morphine-based analgesia is effective but can compromise donor safety. We investigated whether continuous infusion of local anesthetics (CILA) can provide sufficient pain control and reduce morbidity related to opiate analgesics after hand-assisted retroperitoneoscopic (HARS) live donor nephrectomy. Forty consecutive live kidney donors underwent HARS and were treated with the ON-Q system providing CILA with 0.5% ropivacaine through two SilvaGard® catheters placed in the retroperitoneal cavity and the rectus sheath, respectively. The case control group consisted of 40 donors matched with regard to sex, age, BMI and surgical technique. All donors were maintained on standardized multimodal analgesia combining nurse-controlled oxycodone treatment and acetaminophen. CILA donors had lower median cumulative consumption of morphine equivalents (CCME) (7 mg [0-56] vs. 42 mg [15-127]; p < 0.0000001), lower incidence of nausea (18 [45%] vs. 35 [87.5%] donors; p < 0.001), shorter time in postoperative care unit (160 vs. 242.5 min; p < 0.001) and shorter hospital stay (4 [4-7] vs. 6 [4-11] days; p < 0.001). In 32.5% of CILA donors the CCME was 0 mg (0% in matched control group, p < 0.001). CILA with 0.5% ropivacaine provides effective postoperative pain relief, reduces the need for opioid treatment and promotes postoperative recovery. Continuous local infusion of ropivacaine provides sufficient analgesia and opioid-sparing effect as well as reduces the incidence of nausea and vomiting after hand-assisted retroperitoneoscopic live donor nephrectomy.
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| 9. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Liver regeneration is impaired by FK778 in partially hepatectomized rats, while supplemental uridine restores both liver growth and hepatocyte proliferation
- 2009
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Ingår i: Hepatology Research. - 1386-6346 .- 1872-034X. ; 39:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Aim:The impact of mandatory immunosuppression on liver regeneration after segmental liver transplantation is of clinical importance. FK778, a novel immunosuppressant, inhibits pyrimidine biosynthesis and prevents rejection after organ transplantation in a dose-dependent manner. We investigated the effect of FK778 at a highly effective dose on liver regeneration in a small animal model.Methods: Inbred Lewis rats were subjected to 70% partial hepatectomy (PH) and treated with saline (n = 28), uridine (n = 16), FK778 alone (n = 28) or in combination with uridine (n = 16). FK778 was given intravenously daily at a dose of 25 mg/kg bodyweight (bw) and uridine was given daily intraperitoneally at a dose of 250 mg/kg bw. Liver bodyweight ratio (LBR), hepatocyte proliferation index (PI), blood chemistry and morphological analysis were incorporated. PI was determined by Ki-67 immunostaining. De Ritis ratio was calculated to assess the extent of liver damage.Results:In FK778-treated animals PI was decreased at 24 h and 72 h and LBR was lower at 48 h and 72 h (P < 0.05) after the PH. In addition, morphological analysis showed confluent central lobular necrosis at 72 h in four of seven animals. Uridine supplementation restored PI, LBR and the de Ritis ratio in FK778-treated animals and no confluent necroses were observed.Conclusion:FK778 is antihepatotrophic as well as antiproliferative during rat liver regeneration. Both liver growth and hepatocyte proliferation are completely restored by supplementation with uridine. In addition, supplemental uridine markedly reduces the severity of morphological abnormalities consistent with FK778 toxicity.
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| 10. |
- Biglarnia, Ali-Reza, 1973-
(författare)
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Minimizing Risks and Morbidity in Live Kidney Donors
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Live kidney donors are healthy volunteers who are exposed to major surgical procedure and physical harms with no direct therapeutic benefits. Efforts to minimize their risks and morbidity are therefore of utmost importance. The current thesis describes studies on donor evaluation, surgical procedure and postoperative management of live kidney donors. The overall purpose is to evaluate and possibly improve routines and treatments in order to reduce risks and the overall morbidity of live kidney donors. In Study I, we evaluated the assessment of kidney function during donor evaluation and found that the accuracy of iohexol glomerular filtration rate (GFR) is compromised by large variations in repeated measurements in presumably healthy donors. We proposed that there is a need for improvement of GFR measurements and that the assessment of predonation kidney function should be more comprehensive, involving GFR, laboratory investigations, functional and morphological examinations and sound clinical judgment. In Study II, we addressed the risk of perioperative venous thromboembolism (VTE) and concluded that expanding the standard screening protocol for VTE to include perioperative venous duplex can potentially decrease the VTE-related morbidity. In studies III and IV, we investigated the impact of hand-assisted retroperitoneoscopic (HARS) nephrectomy on donor safety and perioperative morbidity. The HARS nephrectomy uses the hand-assisted approach, which enables immediate manual compression for hemostasis in case of sudden and severe bleeding. Additionally, the pure retroperitoneal access further increases the safety margin of laparoscopic donor nephrectomy by 1) minimizing the risk of intestinal injury, and 2) exposure of the retroperitoneal nerves, making HARS suitable for continuous infusion of local anesthetics (CILA). CILA effectively reduces the need for opioid consumption and has the potential to totally obviate opiate analgesics postoperatively. Consequently, CILA in combination with HARS reduces morphine-related morbidity and promotes postoperative recovery. In accordance with these data, we recommend improvement and modification of the donor evaluation process as well as a broad introduction of HARS nephrectomy in combination with CILA to increase the safety margin for live kidney donors.
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| 11. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
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Ingår i: Transplant International. - : John Wiley & Sons. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
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Tidskriftsartikel (refereegranskat)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
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| 12. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
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Tidskriftsartikel (refereegranskat)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
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| 13. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Pulmonary Nocardiosis with Brain Abscess in a Sensitized Kidney Transplant Recipient with a History of Repeated Graft Loss and HLA-Antibody Depletion Treatment : A case report
- 2008
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 113:1, s. 111-116
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Tidskriftsartikel (refereegranskat)abstract
- Nocardiosis is an opportunistic infection with unfavourable prognosis and is predominantly seen in immunocompromised patients. We here present a kidney transplant recipient with a history of two early graft losses who subsequently developed Human Leukocyte Antigen (HLA)-antibodies and underwent a desensitization treatment with plasmapheresis and monoclonal anti-CD20 antibody application. However, 3 months after a third HLA-identical kidney transplantation he developed Nocardiosis with pulmonary and asymptomatic brain manifestation. The present case report exemplifies this opportunistic infection and gives an overview of the literature.
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| 14. |
- Biglarnia, Ali-Reza
(författare)
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Retroperitoneoscopic Hand-Assisted Live Donor Nephrectomy - a Single Center Experience
- 2013
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Ingår i: Annals of Saudi Medicine. - 0256-4947 .- 0975-4466. ; 33:2, s. S86-S90
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Hand-assisted retroperitoneoscopic live donor nephrectomy (HARS) increases the safety margin of live kidney donors by combining hand-assistance with pure retroperitoneal access to the kidney. Furthermore, HARS enables effective and safe non-morphine based analgesia with continuous infusion of local anesthetics (CILA), which potentially adds further safety advantage by reduction of morphine-related complications. This report emphasizes the impact of HARS on donor safety and presents a 12-years experience with the procedure at the University Hospital in Uppsala. MATERIAL AND METHODS : A literature review of relevant reports on HARS is presented. Furthermore, latest unpublished in-house data on HARS nephrectomy procedures from 2010 and 2012 are analyzed for operative characteristics, donor outcome as well as kidney function. RESULTS : Since 2000, HARS is the default donor nephrectomy procedure at our center. Within 12 years, 344 HARS nephrectomies were performed. The overall conversion rate to open surgery was 0.3% (1 out of 344). Between January 2010 and December 2012, 122 HARS and 1 open nephrectomy (anterior incision) were performed. Sixteen donors (13%) were right-sided HARS. After matching for sex, BMI and vascular anatomy, the mean operative time for right and left-sided HARS were 125 minutes (75-175) and 153 minutes (113-251), respectively. The overall mean operative time was 150 minutes (60-251). No donor presented early or late intra-abdominal complications, which is in consistent with our previous reports. The overall morbidity rate was 7.2%. All 122 HARS donors were treated with CILA. The overall mean total cumulative consumption of morphine equivalents (CCME) was 12.4 mg (0-240), while 107 donors (87%) received a total CCME of less than 20 mg. Thirty-four donors (28%) received no morphine equivalents during the hospitalization CONCLUSION : HARS is a safe procedure that virtually eliminates the risk for intra-abdominal complications. The intrinsic advantage for non-morphine based analgesia in combination with excellent donor outcome make this technique eligible for a broader implementation.
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| 15. |
- Biglarnia, Ali Reza, et al.
(författare)
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The multifaceted role of complement in kidney transplantation
- 2018
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Ingår i: Nature Reviews Nephrology. - : Nature Publishing Group. - 1759-5061 .- 1759-507X. ; 14:12, s. 767-781
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Forskningsöversikt (refereegranskat)abstract
- Increasing evidence indicates an integral role for the complement system in the deleterious inflammatory reactions that occur during critical phases of the transplantation process, such as brain or cardiac death of the donor, surgical trauma, organ preservation and ischaemia-reperfusion injury, as well as in humoral and cellular immune responses to the allograft. Ischaemia is the most common cause of complement activation in kidney transplantation and in combination with reperfusion is a major cause of inflammation and graft damage. Complement also has a prominent role in antibody-mediated rejection (ABMR) owing to ABO and HL A incompatibility, which leads to devastating damage to the transplanted kidney. Emerging drugs and treatment modalities that inhibit complement activation at various stages in the complement cascade are being developed to ameliorate the damage caused by complement activation in transplantation. These promising new therapies have various potential applications at different stages in the process of transplantation, including inhibiting the destructive effects of ischaemia and/or reperfusion injury, treating ABMR, inducing accommodation and modulating the adaptive immune response.
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| 16. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Transplantation av pankreas botande alternativ vid typ 1-diabetes : [Transplantation of pancreas, a curative option for type 1 diabetes]
- 2012
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:39-40, s. 1754-1757
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Tidskriftsartikel (refereegranskat)abstract
- In the past decade, pancreas transplantation (PTx) has become increasingly attractive as a curative treatment in patients with labile diabetes and secondary complications. In the United Kingdom, the percentage of deceased-donors utilized for PTx increased 5-fold between 2003 and 2007. The trend towards a higher number of annual pancreas transplantations is also observed in Sweden. The increasing activity and the excellent outcome are consequences of meticulous surgery, effective immunsuppression and adequate follow-up. The present report descibes the current status of PTx and shows the short- and long-term results during the last decade in Sweden.
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| 17. |
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| 18. |
- Laučytė-Cibulskienė, Agnė, et al.
(författare)
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Updated Pathways in Cardiorenal Continuum after Kidney Transplantation
- 2022
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Ingår i: Transplantology. - : MDPI AG. - 2673-3943. ; 3:2, s. 156-168
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Forskningsöversikt (refereegranskat)abstract
- Cardiovascular disease (CVD) remains one of the leading causes for increased morbidity and mortality in chronic kidney disease (CKD). Kidney transplantation is the preferred treatment option for CKD G5. Improved perioperative and postoperative care, personalized immunosuppressive regimes, and refined matching procedures of kidney transplants improves cardiovascular health in the early posttransplant period. However, the long-term burden of CVD is considerable. Previously underrecognized, the role of the complement system alongside innate immunity, inflammaging, structural changes in the glomerular filtration barrier and early vascular ageing also seem to play an important role in the posttransplant management. This review provides up-to-date knowledge on these pathways that may influence the cardiovascular and renal continuum and identifies potential targets for future therapies. Arterial destiffening strategies and the applicability of sodium-glucose cotransporter 2 inhibitors and their role in cardiovascular health after kidney transplantation are also addressed.
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| 19. |
- Lundqvist, Eva, et al.
(författare)
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Measurement of transplanted pancreatic volume using computed tomography : reliability by intra- and inter-observer variability
- 2012
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 53:9, s. 966-972
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundUnlike other solid organ transplants, pancreas allografts can undergo a substantial decrease in baseline volume after transplantation. This phenomenon has not been well characterized, as there are insufficient data on reliable and reproducible volume assessments. We hypothesized that characterization of pancreatic volume by means of computed tomography (CT) could be a useful method for clinical follow-up in pancreas transplant patients.PurposeTo evaluate the feasibility and reliability of pancreatic volume assessment using CT scan in transplanted patients.Material and MethodsCT examinations were performed on 21 consecutive patients undergoing pancreas transplantation. Volume measurements were carried out by two observers tracing the pancreatic contours in all slices. The observers performed the measurements twice for each patient. Differences in volume measurement were used to evaluate intra- and inter-observer variability.ResultsThe intra-observer variability for the pancreatic volume measurements of Observers 1 and 2 was found to be in almost perfect agreement, with an intraclass correlation coefficient (ICC) of 0.90 (0.77-0.96) and 0.99 (0.98-1.0), respectively. Regarding inter-observer validity, the ICCs for the first and second measurements were 0.90 (range, 0.77-0.96) and 0.95 (range, 0.85-0.98), respectively.ConclusionCT volumetry is a reliable and reproducible method for measurement of transplanted pancreatic volume.
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| 20. |
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| 21. |
- Malago, Massimo, et al.
(författare)
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Hepatic venous outflow reconstruction in right live donor liver transplantation.
- 2005
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Ingår i: Liver transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 11:3, s. 364-5
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Tidskriftsartikel (refereegranskat)abstract
- The increasing experience with live donor liver transplantation has allowed for the identification of potential morbidities associated with technical considerations. Technical graft failure can be associated with both inflow and outflow vascular compromise. Although the latter has not always been given the relevance of the former, evidence pointing to its pivotal role continues to mount. We believe that impaired venous outflow was a cause of previously unexplained graft failures during our initial experience. Based on this observation, we developed a technique to prevent the "choking" of the graft at the outflow anastomosis with the inferior vena cava (IVC). The enhanced outflow via a cloaca maximum is achieved by reconstructing the graft vessels with preserved veins or arteries (usually iliac vessels are used) from a blood-group-identical or blood-group-compatible deceased organ donor. Alternatively, hepatic vein or portal vein obtained from the resected native liver can be used. The reconstructed common outflow is anastomosed to a triangular opening of the IVC. Such enhanced outflow provides optimal venous drainage, especially during the early phase of growth of the graft.
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| 22. |
- Mastellos, Dimitrios C., et al.
(författare)
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Taming hemodialysis-induced inflammation : Are complement C3 inhibitors a viable option?
- 2019
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616. ; 198, s. 102-105
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Tidskriftsartikel (refereegranskat)abstract
- Owing to an increasing shortage of donor organs, the majority of patients with end-stage kidney disease remains reliant on extracorporeal hemodialysis (HD) in order to counter the lifelong complications of a failing kidney. While HD remains a life-saving option for these patients, mounting evidence suggests that it also fuels a vicious cycle of thromboinflammation that can increase the risk of cardiovascular disease. During HD, blood-borne innate immune systems become inappropriately activated on the biomaterial surface, instigating proinflammatory reactions that can alter endothelial and vascular homeostasis. Complement activation, early during the HD process, has been shown to fuel a multitude of detrimental thromboinflammatory reactions that collectively contribute to patient morbidity. Here we discuss emerging aspects of complement's involvement in HD-induced inflammation and put forth the concept that targeted intervention at the level of C3 might constitute a promising therapeutic approach in HD patients.
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| 23. |
- Nadalin, Silvio, et al.
(författare)
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Role and significance of plasma citrulline in the early phase after small bowel transplantation in pigs
- 2007
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 20:5, s. 425-431
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Tidskriftsartikel (refereegranskat)abstract
- A reliable serological marker of acute cellular rejection (ACR) after small bowel transplantation (SBTx) is still missing. Plasma citrulline level (PCL) reflects the functional integrity of intestinal mucosa which is partially lost during ACR. The aim of our study was to investigate the role of PCL as marker of ACR after SBTx. Eighteen German landrace pigs were used and divided into three groups. Group 1 (G1), autologous SBTx (n = 4) as control; group 2 (G2), allogeneic SBTx without immunosuppression (IS) (n = 7) and group 3 (G3), allogeneic SBTx with IS (n = 7). IS consisted of tacrolimus and steroids without induction treatment. Observation period was 14 days. Mucosal biopsies were obtained intraoperatively and daily using a Thiry-Vella loop. ACR was differentiated into indeterminate, mild, moderate and severe using a standardized grading schema. PCL was measured daily. An ACR onset occurred generally from postoperative day 4 both in G2 and G3 as mild form and developed differently in the two groups: moderate to severe in G2 and indeterminate to mild in G3. A significant decline of PCL occurred only in cases of moderate and severe ACR, but not in cases of indeterminate and mild ACR. The PCL failed as a marker in the early diagnosis of ACR and became reliable only when advanced mucosal damage was present.
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| 24. |
- Reis, Edimara S., et al.
(författare)
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Safety profile after prolonged C3 inhibition
- 2018
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Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 197, s. 96-106
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Tidskriftsartikel (refereegranskat)abstract
- The central component of the complement cascade, C3, is involved in various biological functions, including opsonization of foreign bodies, clearance of waste material, activation of immune cells, and triggering of pathways controlling development. Given its broad role in immune responses, particularly in phagocytosis and the clearance of microbes, a deficiency in complement C3 in humans is often associated with multiple bacterial infections. Interestingly, an increased susceptibility to infections appears to occur mainly in the first two years of life and then wanes throughout adulthood. In view of the well-established connection between C3 deficiency and infections, therapeutic inhibition of complement at the level of C3 is often considered with caution or disregarded. We therefore set out to investigate the immune and biochemical profile of non-human primates under prolonged treatment with the C3 inhibitor compstatin (Cp40 analog). Cynomolgus monkeys were dosed subcutaneously with Cp40, resulting in systemic inhibition of C3, for 1 week, 2 weeks, or 3 months. Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40. In fact, Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3. Overall, our data suggest that systemic C3 inhibition in healthy adult non-human primates is not associated with a weakened immune system or susceptibility to infections.
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| 25. |
- Sedigh, Amir, et al.
(författare)
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Initial experience with hypothermic machine perfusion of kidneys from deceased donors in the uppsala region in Sweden
- 2013
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Ingår i: Transplantation Proceedings. - : Elsevier BV. - 0041-1345 .- 1873-2623. ; 45:3, s. 1168-71
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 26. |
- Strandberg, Gabriel, et al.
(författare)
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Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes
- 2023
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Ingår i: KIDNEY INTERNATIONAL REPORTS. - : Elsevier. - 2468-0249. ; 8:12, s. 2592-2602
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes.Methods: In a cohort study, 63 patients undergoing LD (n = 26) and DD (n = 37) transplantation were prospectively included. Fifteen DD kidneys were preserved with hypothermic machine perfusion (HMP), and the remaining were cold stored. Activation products of the kallikrein-kinin, coagulation, and complement systems were measured in blood samples obtained systemically at baseline and locally from the transplant renal vein at 1, 10, and 30 minutes after reperfusion.Results: DD kidneys exhibited a prompt and interlinked activation of all 3 cascade systems of IIIS post-reperfusion, indicating a robust and local thrombo-inflammatory response to IRI. In this initial response, the complement activation product sC5b-9 exhibited a robust correlation with other IIIS activation markers and displayed a strong association with short-term and mid-term (24-month) graft dysfunction. In contrast, LD kidneys did not exhibit this thrombo-inflammatory response. The use of HMP was associated with reduced thromboinflammation and preserved mid-term kidney function.Conclusion: Kidneys from DD are vulnerable to a prompt thrombo-inflammatory response to IRI, which adversely affects both short-term and long-term allograft function. Strategies aimed at minimizing graft immunogenicity prior to reperfusion are crucial to mitigate the intricate inflammatory response to IRI.
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| 27. |
- Söfteland, John M., 1977, et al.
(författare)
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Intestinal Preservation Injury: A Comparison Between Rat, Porcine and Human Intestines.
- 2019
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 20:13
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Tidskriftsartikel (refereegranskat)abstract
- Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, whereas clinical translation mandates studies in larger animals or using human material. Despite diverging reports, no direct comparison between the development of intestinal PI in rats, pigs, and humans is available. We compared the development of PI in rat, porcine, and human intestines. Intestinal procurement and cold storage (CS) using histidine-tryptophan-ketoglutarate solution was performed in rats, pigs, and humans. Tissue samples were obtained after 8, 14, and 24 h of CS), and PI was assessed morphologically and at the molecular level (cleaved caspase-3, zonula occludens, claudin-3 and 4, tricellulin, occludin, cytokeratin-8) using immunohistochemistry and Western blot. Intestinal PI developed slower in pigs compared to rats and humans. Tissue injury and apoptosis were significantly higher in rats. Tight junction proteins showed quantitative and qualitative changes differing between species. Significant interspecies differences exist between rats, pigs, and humans regarding intestinal PI progression at tissue and molecular levels. These differences should be taken into account both with regards to study design and the interpretation of findings when relating them to the clinical setting.
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| 28. |
- van Griensven, Martijn, et al.
(författare)
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PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK
- 2019
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Ingår i: Shock. - Alphen aan den Rijn : LIPPINCOTT WILLIAMS & WILKINS. - 1073-2322 .- 1540-0514. ; 51:1, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course afterHS. Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated nonhuman primates (NHP; cynomolgusmonkeys) received a pressure-controlled severe HS (60min at mean arterial pressure 30 mmHg) with subsequent volume resuscitation. Thirty minutes after HS, animals were randomly treated with either an analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n =4) or with saline alone (n =4). The observation period lasted 300 min after induction of HS. We observed improved kidney function in compstatin Cp40-treated animals after HS as determined by improved urine output, reduced damage markers and a tendency of less histopathological signs of acute kidney injury. Sham-treated animals revealed classical signs ofmucosal edema, especially in the ileum and colon reflected by worsened microscopic intestinal injury scores. In contrast, Cp40-treated HS animals exhibited only minor signs of organ edema and significantly less intestinal damage. Furthermore, early systemic inflammation and coagulation dysfunction were both ameliorated by Cp40. The data suggest that therapeutic inhibition of C3 is capable to significantly improve immune, coagulation, and organ function and to preserve organ-barrier integrity early after traumatic HS. C3-targeted complement inhibition may therefore reflect a promising therapeutic strategy in fighting fatal consequences of HS.
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| 29. |
- Wadström, Jonas, et al.
(författare)
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Introducing hand-assisted retroperitoneoscopic live donor nephrectomy : Learning curves and development based on 413 consecutive cases in four centers
- 2011
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 91:4, s. 462-469
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 30. |
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