Induction therapy reduces the frequency of acute rejection and delayed graft function after transplantation. A rabbit antithymocyte polyclonal antibody or basiliximab, an interleukin-2 receptor ...monoclonal antibody, is most commonly used for induction.
In this prospective, randomized, international study, we compared short courses of antithymocyte globulin and basiliximab in patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor. Patients taking cyclosporine, mycophenolate mofetil, and prednisone were randomly assigned to receive either rabbit antithymocyte globulin (1.5 mg per kilogram of body weight daily, 141 patients) during transplantation (day 0) and on days 1 through 4 or basiliximab (20 mg, 137 patients) on days 0 and 4. The primary end point was a composite of acute rejection, delayed graft function, graft loss, and death.
At 12 months, the incidence of the composite end point was similar in the two groups (P=0.34). The antithymocyte globulin group, as compared with the basiliximab group, had lower incidences of acute rejection (15.6% vs. 25.5%, P=0.02) and of acute rejection that required treatment with antibody (1.4% vs. 8.0%, P=0.005). The antithymocyte globulin group and the basiliximab group had similar incidences of graft loss (9.2% and 10.2%, respectively), delayed graft function (40.4% and 44.5%), and death (4.3% and 4.4%). Though the incidences of all adverse events, serious adverse events, and cancers were also similar between the two groups, patients receiving antithymocyte globulin had a greater incidence of infection (85.8% vs. 75.2%, P=0.03) but a lower incidence of cytomegalovirus disease (7.8% vs. 17.5%, P=0.02).
Among patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor, induction therapy consisting of a 5-day course of antithymocyte globulin, as compared with basiliximab, reduced the incidence and severity of acute rejection but not the incidence of delayed graft function. Patient and graft survival were similar in the two groups. (ClinicalTrials.gov number, NCT00235300 ClinicalTrials.gov.).
Long-term use of immunosuppressants is associated with significant morbidity and mortality in transplant recipients. A simple whole blood assay that has U.S. Food and Drug Administration clearance ...directly assesses the net state of immune function of allograft recipients for better individualization of therapy. A meta-analysis of 504 solid organ transplant recipients (heart, kidney, kidney-pancreas, liver and small bowel) from 10 U.S. centers was performed using the Cylex ImmuKnow assay.
Blood samples were taken from recipients at various times posttransplant and compared with clinical course (stable, rejection, infection). In this analysis, 39 biopsy-proven cellular rejections and 66 diagnosed infections occurred. Odds ratios of infection or rejection were calculated based on measured immune response values.
A recipient with an immune response value of 25 ng/ml adenosine triphosphate (ATP) was 12 times (95% confidence of 4 to 36) more likely to develop an infection than a recipient with a stronger immune response. Similarly, a recipient with an immune response of 700 ng/ml ATP was 30 times (95% confidence of 8 to 112) more likely to develop a cellular rejection than a recipient with a lower immune response value. Of note is the intersection of odds ratio curves for infection and rejection in the moderate immune response zone (280 ng/ml ATP). This intersection of risk curves provides an immunological target of immune function for solid organ recipients.
These data show that the Cylex ImmuKnow assay has a high negative predictive value and provides a target immunological response zone for minimizing risk and managing patients to stability.
Lost in Transmission Brehmer, Bernhard; Treffers-Daller, Jeanine
2020, 2020-05-15, Letnik:
59
eBook
This volume makes a key contribution to the description and explanation of variability in the outcomes of heritage language acquisition, taking into account a wide range of factors which impact on ...language acquisition.
Risk of malignancy with long-term immunosuppression in renal transplant recipients.
Improvements in immunosuppressive regimens have significantly enhanced patient and graft survival in renal ...transplant recipients. However, susceptibility to neoplastic disorders is increased as a consequence of prolonged immunosuppression. Available data pertaining to cancer risks in renal transplant recipients have been inconsistent, and much of it is derived from international studies, which may not be truly representative of the United States population.
We studied a total of 1979 transplants performed in 1739 patients from a single center in the United States with a mean follow-up of 6.1 years, and a total of 9852 person-years' follow-up.
The mean age at the time of diagnosis of cancer was 50 years, and the mean interval between transplant and diagnosis of cancer was 95 months. Older patients receiving a transplant had a significantly higher risk for developing cancer as opposed to younger patients (RR 6.2 for >60 years compared with <40 years). When compared with the general population using data from the Surveillance, Epidemiology and End Results (SEER) registry, the overall risk for nonskin malignancies was modestly increased in our transplant recipients, with a standardized incidence ratio (SIR) of 1.4 (P = 0.01). When stratified by age groups, younger age at transplant (<40 years) had the highest SIR, at 2.3 (P < 0.001). Similarly, duration post-transplant >10 years had an SIR of 2.4 (P < 0.001).
We believe that this study is representative of the United States' renal transplant population, and highlights the need for reduced immunosuppression in the long-term and increased vigilance for cancers in younger patients receiving renal transplantation.
Although varicose veins are a common cause of morbidity, etiologic factors predisposing to dilatation, elongation, and tortuosity of the saphenous vein and its tributaries are poorly understood. We ...compared histologic features of normal and varicose saphenous veins and investigated the role of enzyme or inhibitor imbalance in development of varicosities.
Eight normal and 10 varicose (C
2,3E
P,SA
SP
R,O) vein segments were used for this analysis. Matrix metalloproteinase (MMP) expression and activity were analyzed with Western blotting and zymography. Venous architecture and protein localization were determined with histology and immunohistochemistry.
Western blot analysis demonstrated the presence of MMP- 1, MMP-2, MMP-9, and MMP-12, as well as small quantities of tissue inhibitor of metalloproteinases (TIMP)–1 and TIMP-2 in protein isolates from normal and varicose veins. Both vein types demonstrated MMP-2, MMP-9, and MMP-12 activity by gelatin zymography, although varicose vein expressed less MMP-9 activity than normal vein did. Compared with normal veins, changes in varicose veins were not uniformly distributed along the circumference; areas of intimal thickening were often interspersed with focal areas of dilatation. Fragmentation of elastic lamellae and loss of circular and longitudinal muscle fibers were evident in the varicosities. Focal aggregates of macrophages were detected within the media and adventitia of both normal and varicose veins. MMP-1 and MMP-9 were expressed in both types of vein segments; however, their immunohistochemical localization was distinctly different. In normal vein, endothelial cells, occasional smooth muscle cells (SMC), and adventitial microvessels expressed MMP-1, whereas its expression was localized to fibroblasts, SMC, and endothelial cells throughout involved portions of varicose veins. MMP-9 was localized to endothelial cells, medial SMC, and adventitial microvessels in both normal and varicose veins, although varicose veins demonstrated increased medial smooth muscle cell staining. MMP-12 was found in SMC and fibroblasts in both normal and varicose veins. Neither TIMP-1 nor TIMP-2 were detected with immunohistochemistry in any specimens examined.
There are distinct differences in the structural architecture and localization of MMP expression in normal and varicose veins. Although the changes observed are not sufficiently definitive to enable a causal relationship, they do suggest a possible mechanism for the alterations in matrix composition observed between normal and varicose veins.
Who’s My Doctor? Jayarajan, Senthil, M.D; Daller, John A., M.D., Ph.D., F.A.C.S
The Journal of surgical research,
11/2011, Letnik:
171, Številka:
1
Journal Article
Purpose
: This study sought to define management strategies based on clinical experience in treating infantile hepatic hemangioendothelioma.
Methods
: A retrospective analysis of patients with ...hemangioendothelioma presenting to a tertiary liver transplantation center between 1989 and 1997 was performed.
Results
: Thirteen patients (median age, 14 days) with hemangioendothelioma were identified. Congestive heart failure (
P<.03) and abdominal mass (
P<.081) were predictive of 5-month mortality rates. Ultrasonography and computerized axial tomography were the diagnostic modalities most commonly used. Treatment strategies consisted of medical management (steroids and α-interferon) and interventional modalities (hepatic artery ligation or embolization, resectional surgery, or orthotopic liver transplantation). Patients who underwent resectional surgery, with or without orthotopic liver transplantation, had a lower 5-month mortality rate (
P<.02) and a greater 2-year survival rate (
P<.003) than did those who underwent hepatic artery ligation or embolization. Early morbidity and mortality tended to be a consequence of the primary lesion, whereas late morbidity and mortality were reflective of the treatment modality used.
Conclusions
: In cases of failed medical management, resectional therapy should be used when possible. If partial hepatectomy is not technically achievable, hepatic artery embolization should be used either as definitive therapy or as a temporizing measure until orthotopic liver transplantation is possible.
End-stage renal disease (ESRD) patients with antiphospholipid antibody syndrome (APAS) remain at high risk for the development of renal thrombosis without the benefit of anticoagulation therapy. This ...study examines the efficacy of anticoagulation therapy in this high-risk patient population.
Of nine APAS renal-transplant patients, seven were treated with coumadin, whereas two were treated with heparin.
Of the two patients treated with heparin, one had early allograft loss, whereas the other patient is doing fine at 5 years posttransplant. Of the seven 7 patients treated with coumadin, two patients are doing well at 2 and 3 years posttransplant, two had early allograft loss, the remaining three patients returned to dialysis after they were taken off of the coumadin at 6, 12, and 20 months posttransplant because of bleeding complications.
Anticoagulation therapy is beneficial to some but not all APAS patients. In addition, bleeding complications are a serious side effect of this therapy.
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