Pub Date : 2017-01-01Epub Date: 2017-09-24DOI: 10.1155/2017/8132672
Alfonso H Santos, Michael J Casey, Karl L Womer
We studied registry data of 12,944 adult kidney retransplant recipients categorized by induction regimen received into antithymocyte globulin (ATG) (N = 9120), alemtuzumab (N = 1687), and basiliximab (N = 2137) cohorts. We analyzed risk factors for 1-year acute rejection (AR) and 5-year death-censored graft loss (DCGL) and patient death. Compared with the reference, basiliximab: (1) one-year AR risk was lower with ATG in retransplant recipients of expanded criteria deceased-donor kidneys (HR = 0.56, 95% CI = 0.35-0.91 and HR = 0.54, 95% CI = 0.27-1.08, resp.), while AR risk was lower with alemtuzumab in retransplant recipients with >3 HLA mismatches before transplant (HR = 0.63, 95% CI = 0.44-0.93 and HR = 0.81, 95% CI = 0.63-1.06, resp.); (2) five-year DCGL risk was lower with alemtuzumab, not ATG, in retransplant recipients of African American race (HR = 0.54, 95% CI = 0.34-0.86 and HR = 0.73, 95% CI = 0.51-1.04, resp.) or with pretransplant glomerulonephritis (HR = 0.65, 95% CI = 0.43-0.98 and HR = 0.82, 95% CI = 0.60-1.12, resp.). Therefore, specific risk factor-induction regimen combinations may predict outcomes and this information may help in individualizing induction in retransplant recipients.
我们研究了 12,944 名成人肾脏再移植受者的登记数据，这些受者按所接受的诱导方案分为抗胸腺细胞球蛋白 (ATG) 组（N = 9120）、阿利珠单抗组（N = 1687）和巴利昔单抗组（N = 2137）。我们分析了1年急性排斥反应（AR）和5年死亡校正移植物丢失（DCGL）以及患者死亡的风险因素。与参照物巴利昔单抗相比：(1) ATG在扩大标准死者供肾再移植受者中的1年AR风险较低（HR = 0.56，95% CI = 0.35-0.91和HR = 0.54，95% CI = 0.27-1.08），而阿来珠单抗在移植前HLA错配>3的再移植受者中的AR风险较低（HR = 0.63，95% CI = 0.44-0.93和HR = 0.81，95% CI = 0.63-1.06，resp.）；（2）在非裔美国人种的再移植受者中，阿仑珠单抗的5年DCGL风险较低（HR = 0.54，95% CI = 0.34-0.86 和 HR = 0.73，95% CI = 0.51-1.04，resp.）或有移植前肾小球肾炎（HR = 0.65，95% CI = 0.43-0.98 和 HR = 0.82，95% CI = 0.60-1.12，resp.）。因此，特定的风险因素-诱导方案组合可预测预后，这一信息有助于对再移植受者进行个体化诱导。
{"title":"Analysis of Risk Factors for Kidney Retransplant Outcomes Associated with Common Induction Regimens: A Study of over Twelve-Thousand Cases in the United States.","authors":"Alfonso H Santos, Michael J Casey, Karl L Womer","doi":"10.1155/2017/8132672","DOIUrl":"10.1155/2017/8132672","url":null,"abstract":"<p><p>We studied registry data of 12,944 adult kidney retransplant recipients categorized by induction regimen received into antithymocyte globulin (ATG) (<i>N</i> = 9120), alemtuzumab (<i>N</i> = 1687), and basiliximab (<i>N</i> = 2137) cohorts. We analyzed risk factors for 1-year acute rejection (AR) and 5-year death-censored graft loss (DCGL) and patient death. Compared with the reference, basiliximab: (1) one-year AR risk was lower with ATG in retransplant recipients of expanded criteria deceased-donor kidneys (HR = 0.56, 95% CI = 0.35-0.91 and HR = 0.54, 95% CI = 0.27-1.08, resp.), while AR risk was lower with alemtuzumab in retransplant recipients with >3 HLA mismatches before transplant (HR = 0.63, 95% CI = 0.44-0.93 and HR = 0.81, 95% CI = 0.63-1.06, resp.); (2) five-year DCGL risk was lower with alemtuzumab, not ATG, in retransplant recipients of African American race (HR = 0.54, 95% CI = 0.34-0.86 and HR = 0.73, 95% CI = 0.51-1.04, resp.) or with pretransplant glomerulonephritis (HR = 0.65, 95% CI = 0.43-0.98 and HR = 0.82, 95% CI = 0.60-1.12, resp.). Therefore, specific risk factor-induction regimen combinations may predict outcomes and this information may help in individualizing induction in retransplant recipients.</p>","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2017 ","pages":"8132672"},"PeriodicalIF":2.5,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35719010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-02-20DOI: 10.1155/2017/6347138
Jan Van Keer, David Derthoo, Olivier Van Caenegem, Michel De Pauw, Eric Nellessen, Nathalie Duerinckx, Walter Droogne, Gábor Vörös, Bart Meyns, Ann Belmans, Stefan Janssens, Johan Van Cleemput, Johan Vanhaecke
In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30-60 mL/min/1.73 m2) were randomized to start everolimus with CNI withdrawal (N = 29) or continue their current CNI-based immunosuppression (N = 28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.18). In the on-treatment analysis, the difference did reach statistical significance (+9.4 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.047). The composite safety endpoint of all-cause mortality, major adverse cardiovascular events, or treated acute rejection was not different between groups. Nonfatal adverse events occurred in 96.6% of patients in the everolimus group and 57.1% in the CNI group (p < 0.001). Ten patients (34.5%) in the everolimus group discontinued the study drug during follow-up due to adverse events. The poor adherence to the everolimus therapy might have masked a potential benefit of CNI withdrawal on renal function.
{"title":"The CECARI Study: Everolimus (Certican®) Initiation and Calcineurin Inhibitor Withdrawal in Maintenance Heart Transplant Recipients with Renal Insufficiency: A Multicenter, Randomized Trial.","authors":"Jan Van Keer, David Derthoo, Olivier Van Caenegem, Michel De Pauw, Eric Nellessen, Nathalie Duerinckx, Walter Droogne, Gábor Vörös, Bart Meyns, Ann Belmans, Stefan Janssens, Johan Van Cleemput, Johan Vanhaecke","doi":"10.1155/2017/6347138","DOIUrl":"https://doi.org/10.1155/2017/6347138","url":null,"abstract":"<p><p>In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30-60 mL/min/1.73 m<sup>2</sup>) were randomized to start everolimus with CNI withdrawal (<i>N</i> = 29) or continue their current CNI-based immunosuppression (<i>N</i> = 28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, <i>p</i> = 0.18). In the on-treatment analysis, the difference did reach statistical significance (+9.4 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, <i>p</i> = 0.047). The composite safety endpoint of all-cause mortality, major adverse cardiovascular events, or treated acute rejection was not different between groups. Nonfatal adverse events occurred in 96.6% of patients in the everolimus group and 57.1% in the CNI group (<i>p</i> < 0.001). Ten patients (34.5%) in the everolimus group discontinued the study drug during follow-up due to adverse events. The poor adherence to the everolimus therapy might have masked a potential benefit of CNI withdrawal on renal function.</p>","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2017 ","pages":"6347138"},"PeriodicalIF":2.5,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/6347138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34833100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-01-26DOI: 10.1155/2017/5646858
Fernando González, René López, Elizabeth Arriagada, René Carrasco, Natalia Gallardo, Eduardo Lorca
Background. Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch. Methods. Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice. Results. Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did: 1.62 ± 0.90 versus 1.75 ± 0.92 mg/dL (p < 0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period. Conclusion. Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians.
背景。他克莫司是用于肾移植患者的主要免疫抑制药物。在智利卫生部授权实施这一转变后，我们研究了用仿制药替代品牌产品是一个有争议的问题。方法。41例稳定的接受肾移植的Prograf (Astellas)患者以1:1的剂量比例切换到通用的他克莫司(Sandoz)，随访长达8个月。所有其他药物维持正常操作。结果。切换后，他克莫司剂量及其谷血水平均未发生显著变化，但血清肌酐变化明显:1.62±0.90 mg/dL vs 1.75±0.92 mg/dL (p < 0.001)。同时，进行了5例移植活检，其中2例出现细胞急性排斥反应。通过适当的治疗，有9例感染发作得到满意的治疗。随访期间无患者或移植物丢失。结论。从品牌他克莫司切换到非专利他克莫司(山德士)是可行的，似乎是安全的，但必须由治疗医生仔细监测。
{"title":"Switching Stable Kidney Transplant Recipients to a Generic Tacrolimus Is Feasible and Safe, but It Must Be Monitored.","authors":"Fernando González, René López, Elizabeth Arriagada, René Carrasco, Natalia Gallardo, Eduardo Lorca","doi":"10.1155/2017/5646858","DOIUrl":"https://doi.org/10.1155/2017/5646858","url":null,"abstract":"<p><p><i>Background</i>. Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch. <i>Methods</i>. Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice. <i>Results</i>. Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did: 1.62 ± 0.90 versus 1.75 ± 0.92 mg/dL (<i>p</i> < 0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period. <i>Conclusion</i>. Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians.</p>","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2017 ","pages":"5646858"},"PeriodicalIF":2.5,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/5646858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34771961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark R. Pedersen, Myunghan Choi, J. Brink, A. Seetharam
Changes in distribution policies have increased median MELD at transplant with recipients requiring increasing intensive care perioperatively. We aimed to evaluate association of preoperative variables with postoperative respiratory failure (PRF)/increased intensive care unit length of stay (ICU LOS)/short-term survival in a high MELD cohort undergoing liver transplant (LT). Retrospective analysis identified cases of PRF and increased ICU LOS with recipient, donor, and surgical variables examined. Variables were entered into regression with end points of PRF and ICU LOS > 3 days. 164 recipients were examined: 41 (25.0%) experienced PRF and 74 (45.1%) prolonged ICU LOS. Significant predictors of PRF with univariate analysis: BMI > 30, pretransplant MELD, preoperative respiratory failure, LVEF < 50%, FVC < 80%, intraoperative transfusion > 6 units, warm ischemic time > 4 minutes, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted PRF (OR 1.14, p = 0.01). Significant predictors of prolonged ICU LOS with univariate analysis are as follows: pretransplant MELD, FVC < 80%, FEV1 < 80%, deceased donor, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted prolonged ICU LOS (OR 1.28, p < 0.001). One-year survival among cohorts with PRF and increased ICU LOS was similar to subjects without. Pretransplant MELD is a robust predictor of PRF and ICU LOS. Higher MELDs at LT are expected to increase need for ICU utilization and modify expectations for recovery in the immediate postoperative period.
{"title":"Pretransplant Factors and Associations with Postoperative Respiratory Failure, ICU Length of Stay, and Short-Term Survival after Liver Transplantation in a High MELD Population","authors":"Mark R. Pedersen, Myunghan Choi, J. Brink, A. Seetharam","doi":"10.1155/2016/6787854","DOIUrl":"https://doi.org/10.1155/2016/6787854","url":null,"abstract":"Changes in distribution policies have increased median MELD at transplant with recipients requiring increasing intensive care perioperatively. We aimed to evaluate association of preoperative variables with postoperative respiratory failure (PRF)/increased intensive care unit length of stay (ICU LOS)/short-term survival in a high MELD cohort undergoing liver transplant (LT). Retrospective analysis identified cases of PRF and increased ICU LOS with recipient, donor, and surgical variables examined. Variables were entered into regression with end points of PRF and ICU LOS > 3 days. 164 recipients were examined: 41 (25.0%) experienced PRF and 74 (45.1%) prolonged ICU LOS. Significant predictors of PRF with univariate analysis: BMI > 30, pretransplant MELD, preoperative respiratory failure, LVEF < 50%, FVC < 80%, intraoperative transfusion > 6 units, warm ischemic time > 4 minutes, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted PRF (OR 1.14, p = 0.01). Significant predictors of prolonged ICU LOS with univariate analysis are as follows: pretransplant MELD, FVC < 80%, FEV1 < 80%, deceased donor, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted prolonged ICU LOS (OR 1.28, p < 0.001). One-year survival among cohorts with PRF and increased ICU LOS was similar to subjects without. Pretransplant MELD is a robust predictor of PRF and ICU LOS. Higher MELDs at LT are expected to increase need for ICU utilization and modify expectations for recovery in the immediate postoperative period.","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2016 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2016-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/6787854","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64489259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.
{"title":"Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation","authors":"R. Heyes, Andrew Iarocci, Y. Tchoukalova, D. Lott","doi":"10.1155/2016/6951693","DOIUrl":"https://doi.org/10.1155/2016/6951693","url":null,"abstract":"This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2016 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2016-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/6951693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64498032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Fleetwood, J. Lusciks, J. Poirier, M. Hertl, E. Chan
Background. The PHS increased risk donor (IRD) is underutilized in liver transplantation. We aimed to examine the posttransplant outcomes in recipients of increased-risk organs. Methods. We analyzed 228,040 transplants in the Organ Procurement and Transplantation Network database from 2004 to 2013. Endpoints were graft failure and death. Results were controlled for demographics and comorbidities. Statistical analysis utilized Fisher's test and logistic regression. Results. 58,816 patients were identified (5,534 IRD, 53,282 non-IRD). IRDs were more frequently male (69.2% versus 58.3%, p < 0.001), younger (34 versus 39, p < 0.001), and less likely to have comorbidities (p < 0.001). Waitlist time was longer for IRD graft recipients (254 versus 238 days, p < 0.001). All outcomes were better in the IRD group. Graft failure (23.6 versus 27.3%, p < 0.001) and mortality (20.4 versus 22.3%, p = 0.001) were decreased in IRD graft recipients. However, in multivariate analysis, IRD status was not a significant indicator of outcomes. Conclusion. This is the first study to describe IRD demographics in liver transplantation. Outcomes are improved in IRD organ recipients; however, controlling for donor and recipient comorbidities, ischemia time, and MELD score, the differences lose significance. In multivariate analysis, use of IRD organs is noninferior, with similar graft failure and mortality despite the infectious risk.
{"title":"Utilization of Public Health Service Increased Risk Donors Yields Equivalent Outcomes in Liver Transplantation","authors":"V. Fleetwood, J. Lusciks, J. Poirier, M. Hertl, E. Chan","doi":"10.1155/2016/9658904","DOIUrl":"https://doi.org/10.1155/2016/9658904","url":null,"abstract":"Background. The PHS increased risk donor (IRD) is underutilized in liver transplantation. We aimed to examine the posttransplant outcomes in recipients of increased-risk organs. Methods. We analyzed 228,040 transplants in the Organ Procurement and Transplantation Network database from 2004 to 2013. Endpoints were graft failure and death. Results were controlled for demographics and comorbidities. Statistical analysis utilized Fisher's test and logistic regression. Results. 58,816 patients were identified (5,534 IRD, 53,282 non-IRD). IRDs were more frequently male (69.2% versus 58.3%, p < 0.001), younger (34 versus 39, p < 0.001), and less likely to have comorbidities (p < 0.001). Waitlist time was longer for IRD graft recipients (254 versus 238 days, p < 0.001). All outcomes were better in the IRD group. Graft failure (23.6 versus 27.3%, p < 0.001) and mortality (20.4 versus 22.3%, p = 0.001) were decreased in IRD graft recipients. However, in multivariate analysis, IRD status was not a significant indicator of outcomes. Conclusion. This is the first study to describe IRD demographics in liver transplantation. Outcomes are improved in IRD organ recipients; however, controlling for donor and recipient comorbidities, ischemia time, and MELD score, the differences lose significance. In multivariate analysis, use of IRD organs is noninferior, with similar graft failure and mortality despite the infectious risk.","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2016 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2016-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/9658904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64630261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previously, transplantation of ovaries from young cycling mice into old postreproductive-age mice increased life span. We anticipated that the same factors that increased life span could also influence health span. Female CBA/J mice received new (60 d) ovaries at 12 and 17 months of age and were evaluated at 16 and 25 months of age, respectively. There were no significant differences in body weight among any age or treatment group. The percentage of fat mass was significantly increased at 13 and 16 months of age but was reduced by ovarian transplantation in 16-month-old mice. The percentages of lean body mass and total body water were significantly reduced in 13-month-old control mice but were restored in 16- and 25-month-old recipient mice by ovarian transplantation to the levels found in six-month-old control mice. In summary, we have shown that skeletal muscle mass, which is negatively influenced by aging, can be positively influenced or restored by reestablishment of active ovarian function in aged female mice. These findings provide strong incentive for further investigation of the positive influence of young ovaries on restoration of health in postreproductive females.
{"title":"Manipulation of Ovarian Function Significantly Influenced Sarcopenia in Postreproductive-Age Mice","authors":"Rhett L. Peterson, Kate C Parkinson, J. Mason","doi":"10.1155/2016/4570842","DOIUrl":"https://doi.org/10.1155/2016/4570842","url":null,"abstract":"Previously, transplantation of ovaries from young cycling mice into old postreproductive-age mice increased life span. We anticipated that the same factors that increased life span could also influence health span. Female CBA/J mice received new (60 d) ovaries at 12 and 17 months of age and were evaluated at 16 and 25 months of age, respectively. There were no significant differences in body weight among any age or treatment group. The percentage of fat mass was significantly increased at 13 and 16 months of age but was reduced by ovarian transplantation in 16-month-old mice. The percentages of lean body mass and total body water were significantly reduced in 13-month-old control mice but were restored in 16- and 25-month-old recipient mice by ovarian transplantation to the levels found in six-month-old control mice. In summary, we have shown that skeletal muscle mass, which is negatively influenced by aging, can be positively influenced or restored by reestablishment of active ovarian function in aged female mice. These findings provide strong incentive for further investigation of the positive influence of young ovaries on restoration of health in postreproductive females.","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"27 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2016-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/4570842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64387059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. M. Arreola-Guerra, N. Castelán, A. de Santiago, A. Arvizu, Norma González-Tableros, Mayra López, I. Salcedo, M. Vilatoba, J. Granados, L. Morales-Buenrostro, J. Alberú
The aim of the present study was to describe the association of positive flow cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA) and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n = 26, 52%). Ten patients (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80–259.56, P = 0.004, and no DSA C1q+ Ab: OR 5, 1.27–19.68, P = 0.021) and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06–1.49, P = 0.007). The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85–100) and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3–100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity.
本研究的目的是描述正流交叉匹配(FXM)与C1q-SAB的关系。方法。在这项观察性、横断面和比较研究中，纳入的患者AHG-CDC-XM和供体特异性抗体(DSA)均为阴性，并进行了FXM检测。所有移植前血清均采用C1q-SAB检测。结果。总共进行了50次捐助国/受援国评价;半数患者至少有一种C1q+ Ab (n = 26, 52%)。10例(20.0%)DSA C1q+ Ab, 25例(50%)FXMs阳性。与FXM阳性相关的因素是C1q+ Ab的存在(DSA C1q+ Ab: OR 27, 2.80-259.56, P = 0.004，无DSA C1q+ Ab: OR 5, 1.27-19.68, P = 0.021)和DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06-1.49, P = 0.007)。免疫优势的LABScreen SAB DSA-MFI预测FXM的灵敏度和特异性最高的截止点为2300(灵敏度为72%，特异性为75%)。对于FXM的预测，DSA C1q+ Ab的特异性最高(95.8%，85-100)，DSA- mfi bbb2300与C1q+ Ab的联合预测敏感性最高(92.0%，79.3-100)。结论。C1q+ Ab和LABScreen SAB DSA-MFI与FXM显著相关。DSA C1q+ Ab特异度高，敏感性低。
{"title":"C1Q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal Transplant Candidates with Donor-Specific Antibodies: High Specificity but Low Sensitivity When Predicting Flow Crossmatch","authors":"J. M. Arreola-Guerra, N. Castelán, A. de Santiago, A. Arvizu, Norma González-Tableros, Mayra López, I. Salcedo, M. Vilatoba, J. Granados, L. Morales-Buenrostro, J. Alberú","doi":"10.1155/2016/2106028","DOIUrl":"https://doi.org/10.1155/2016/2106028","url":null,"abstract":"The aim of the present study was to describe the association of positive flow cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA) and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n = 26, 52%). Ten patients (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80–259.56, P = 0.004, and no DSA C1q+ Ab: OR 5, 1.27–19.68, P = 0.021) and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06–1.49, P = 0.007). The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85–100) and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3–100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity.","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2016 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2016-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/2106028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64261801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Beal, D. Tumin, L. Conteh, A. Hanje, Anthony J. Michaels, D. Hayes, S. Black, K. Mumtaz
There is a paucity of literature examining recipient-donor obesity matching on liver transplantation outcomes. The United Network for Organ Sharing database was queried for first-time recipients of liver transplant whose age was ≥18 between January 2003 and September 2013. Outcomes including patient and graft survival at 30 days, 1 year, and 5 years and overall, liver retransplantation, and length of stay were compared between nonobese recipients receiving a graft from nonobese donors and obese recipient-obese donor, obese recipient-nonobese donor, and nonobese recipient-obese donor pairs. 51,556 LT recipients were identified, including 34,217 (66%) nonobese and 17,339 (34%) obese recipients. The proportions of patients receiving an allograft from an obese donor were 24% and 29%, respectively, among nonobese and obese recipients. Graft loss (HR: 1.27; 95% CI: 1.09–1.46; p = 0.002) and mortality (HR: 1.38; 95% CI: 1.16–1.65; p < 0.001) at 30 days were increased in the obese recipient-obese donor pair. However, 1-year graft (HR: 0.83; 95% CI: 0.74–0.93; p = 0.002) and patient (HR: 0.84; 95% CI: 0.74–0.95; p = 0.007) survival and overall patient (HR: 0.93; 95% CI: 0.86–1.00; p = 0.042) survival were favorable. There is evidence of recipient and donor obesity disadvantage early, but survival curves demonstrate improved long-term outcomes. It is important to consider obesity in the donor-recipient match.
{"title":"Impact of Recipient and Donor Obesity Match on the Outcomes of Liver Transplantation: All Matches Are Not Perfect","authors":"E. Beal, D. Tumin, L. Conteh, A. Hanje, Anthony J. Michaels, D. Hayes, S. Black, K. Mumtaz","doi":"10.1155/2016/9709430","DOIUrl":"https://doi.org/10.1155/2016/9709430","url":null,"abstract":"There is a paucity of literature examining recipient-donor obesity matching on liver transplantation outcomes. The United Network for Organ Sharing database was queried for first-time recipients of liver transplant whose age was ≥18 between January 2003 and September 2013. Outcomes including patient and graft survival at 30 days, 1 year, and 5 years and overall, liver retransplantation, and length of stay were compared between nonobese recipients receiving a graft from nonobese donors and obese recipient-obese donor, obese recipient-nonobese donor, and nonobese recipient-obese donor pairs. 51,556 LT recipients were identified, including 34,217 (66%) nonobese and 17,339 (34%) obese recipients. The proportions of patients receiving an allograft from an obese donor were 24% and 29%, respectively, among nonobese and obese recipients. Graft loss (HR: 1.27; 95% CI: 1.09–1.46; p = 0.002) and mortality (HR: 1.38; 95% CI: 1.16–1.65; p < 0.001) at 30 days were increased in the obese recipient-obese donor pair. However, 1-year graft (HR: 0.83; 95% CI: 0.74–0.93; p = 0.002) and patient (HR: 0.84; 95% CI: 0.74–0.95; p = 0.007) survival and overall patient (HR: 0.93; 95% CI: 0.86–1.00; p = 0.042) survival were favorable. There is evidence of recipient and donor obesity disadvantage early, but survival curves demonstrate improved long-term outcomes. It is important to consider obesity in the donor-recipient match.","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2016 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/9709430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64634597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Emmanouilidis, Rickmer Peters, B. Ringe, Z. Güner, W. Ramackers, H. Bektas, F. Lehner, M. Manns, J. Klempnauer, H. Schrem
Background. This is a single center oncological resume overlooking four decades of experience with liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods. All 319 LT for HCC that were performed between 1975 and 2011 were included. Predictors for HCC recurrence (HCCR) and survival were identified by Cox regression, Kaplan-Meier analysis, Log Rank, and χ 2-tests where appropriate. Results. HCCR was the single strongest hazard for survival (exp(B) = 10.156). Hazards for HCCR were tumor staging beyond the histologic MILAN (exp(B) = 3.645), bilateral tumor spreading (exp(B) = 14.505), tumor grading beyond G2 (exp(B) = 8.668), and vascular infiltration of small or large vessels (exp(B) = 11.612, exp(B) = 18.324, resp.). Grading beyond G2 (exp(B) = 10.498) as well as small and large vascular infiltrations (exp(B) = 13.337, exp(B) = 16.737, resp.) was associated with higher hazard ratios for long-term survival as compared to liver transplantation beyond histological MILAN (exp(B) = 4.533). Tumor dedifferentiation significantly correlated with vascular infiltration (χ 2 p = 0.006) and intrahepatic tumor spreading (χ 2 p = 0.016). Conclusion. LT enables survival from HCC. HCC dedifferentiation is associated with vascular infiltration and intrahepatic tumor spreading and is a strong hazard for HCCR and survival. Pretransplant tumor staging should include grading by biopsy, because grading is a reliable and easily accessible predictor of HCCR and survival. Detection of dedifferentiation should speed up the allocation process.
{"title":"Liver Transplantation for Hepatocellular Carcinoma: A Single Center Resume Overlooking Four Decades of Experience","authors":"N. Emmanouilidis, Rickmer Peters, B. Ringe, Z. Güner, W. Ramackers, H. Bektas, F. Lehner, M. Manns, J. Klempnauer, H. Schrem","doi":"10.1155/2016/7895956","DOIUrl":"https://doi.org/10.1155/2016/7895956","url":null,"abstract":"Background. This is a single center oncological resume overlooking four decades of experience with liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods. All 319 LT for HCC that were performed between 1975 and 2011 were included. Predictors for HCC recurrence (HCCR) and survival were identified by Cox regression, Kaplan-Meier analysis, Log Rank, and χ 2-tests where appropriate. Results. HCCR was the single strongest hazard for survival (exp(B) = 10.156). Hazards for HCCR were tumor staging beyond the histologic MILAN (exp(B) = 3.645), bilateral tumor spreading (exp(B) = 14.505), tumor grading beyond G2 (exp(B) = 8.668), and vascular infiltration of small or large vessels (exp(B) = 11.612, exp(B) = 18.324, resp.). Grading beyond G2 (exp(B) = 10.498) as well as small and large vascular infiltrations (exp(B) = 13.337, exp(B) = 16.737, resp.) was associated with higher hazard ratios for long-term survival as compared to liver transplantation beyond histological MILAN (exp(B) = 4.533). Tumor dedifferentiation significantly correlated with vascular infiltration (χ 2 p = 0.006) and intrahepatic tumor spreading (χ 2 p = 0.016). Conclusion. LT enables survival from HCC. HCC dedifferentiation is associated with vascular infiltration and intrahepatic tumor spreading and is a strong hazard for HCCR and survival. Pretransplant tumor staging should include grading by biopsy, because grading is a reliable and easily accessible predictor of HCCR and survival. Detection of dedifferentiation should speed up the allocation process.","PeriodicalId":45795,"journal":{"name":"Journal of Transplantation","volume":"2016 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2016-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/7895956","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64538407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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