Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.

PubMed

Uhlin, Michael; Wikell, Helena; Sundin, Mikael; Blennow, Ola; Maeurer, Markus; Ringden, Olle; Winiarski, Jacek; Ljungman, Per; Remberger, Mats; Mattsson, Jonas

2014-02-01

Allogeneic hematopoietic stem cell transplantation is a successful treatment for hematologic malignancies and a variety of genetic and metabolic disorders. In the period following stem cell transplantation, the immune-compromised milieu allows opportunistic pathogens to thrive. Epstein-Barr virus-associated post-transplant lymphoproliferative disease can be a life-threatening complication for transplanted patients because of suppressed T-cell-mediated immunity. We analyzed possible risk factors associated with post-transplant lymphoproliferative disease in a cohort of over 1,000 patients. The incidence of post-transplant lymphoproliferative disease was 4%. Significant risk factors identified by multivariate analysis were: human leukocyte antigen-mismatch (P<0.001), serological Epstein-Barr virus mismatch recipient-/donor+ (P<0.001), use of reduced intensity conditioning (P=0.002), acute graft-versus-host disease grade II to IV (P=0.006), pre-transplant splenectomy (P=0.008) and infusion of mesenchymal stromal cells (P=0.015). The risk of post-transplant lymphoproliferative disease has increased in more recent years, from less than 2% before 1998 to more than 6% after 2011. Additionally, we show that long-term survival of patients with post-transplant lymphoproliferative disease is poor despite initial successful treatment. The 3-year survival rate among the 40 patients with post-transplant lymphoproliferative disease was 20% as opposed to 62% among patients without post-transplant lymphoproliferative disease (P<0.001). The study identifies patients at risk of post-transplant lymphoproliferative disease after transplantation in need of pre-emptive measures.

High early cardiovascular mortality following liver transplantation

PubMed Central

VanWagner, Lisa B.; Lapin, Brittany; Levitsky, Josh; Wilkins, John T.; Abecassis, Michael M.; Skaro, Anton I.; Lloyd-Jones, Donald M.

2014-01-01

Cardiovascular disease (CVD) contributes to excess long-term mortality after liver transplantation (LT), however little is known about early post-operative CVD mortality in the current era. In addition, there is no model to predict early post-operative CVD mortality across centers. We analyzed adult recipients of primary LT in the Organ Procurement and Transplantation Network (OPTN) database between February 2002 and December 2012 to assess prevalence and predictors of early (30-day) CVD mortality, defined as death from arrhythmia, heart failure, myocardial infarction, cardiac arrest, thromboembolism, and/or stroke. We performed logistic regression with stepwise selection to develop a predictive model of early CVD mortality. Sex and center volume were forced into the final model, which was validated using bootstrapping techniques. Among 54,697 LT recipients, there were 1576 (2.9%) deaths within 30 days. CVD death was the leading cause of 30-day mortality (42.1%), followed by infection (27.9%) and graft failure (12.2%). In multivariate analysis, 9 (6 recipient, 2 donor, 1 operative) significant covariates were identified: age, pre-operative hospitalization, ICU and ventilator status, calculated MELD score, portal vein thrombosis, national organ sharing, donor BMI and cold ischemia time. The model showed moderate discrimination (c-statistic 0.66, 95% CI: 0.63–0.68). We provide the first multicenter prognostic model for the prediction of early post-LT CVD death, the most common cause of early post-LT mortality in the current transplant era. However, evaluation of additional CVD-related variables not collected by the OPTN are needed in order to improve model accuracy and potential clinical utility. PMID:25044256

Early post-transplant immune monitoring can predict long-term kidney graft survival: soluble CD30 levels, anti-HLA antibodies and IgA-anti-Fab autoantibodies.

PubMed

Amirzargar, Mohammad Ali; Amirzargar, Aliakbar; Basiri, Abbas; Hajilooi, Mehrdad; Roshanaei, Ghodratollah; Rajabi, Gholamreza; Mohammadiazar, Sina; Solgi, Ghasem

2014-01-01

This study aimed to investigate the predictive power of anti-HLA antibodies, sCD30 levels and IgA-anti-Fab autoantibody before and early after transplantation in relation to long-term kidney allograft survival. Pre- and post-transplant sera samples of 59 living-unrelated donor kidney recipients were tested for above risk factors by enzyme-linked immunoabsorbent assay. 15 out of 59 cases experienced rejection episodes (failure group). Pre- and post-transplant high sCD30 levels were significantly associated with graft failure (P=0.02 and P=0.004) and decreased 4 year graft survival (P = 0.009 and P = 0.001). Higher frequency of post-transplant HLA class-II antibody in the absence of class-I antibody was observed in failure group (P=0.007). Patients with post-transplant HLA class-I and class-II antibodies either alone or in combination showed significant lower 4 year graft survival. Recipients with high sCD30 levels in the presence of HLA class-I or class-II antibodies within 2 weeks post-transplant had poor graft survival (P = 0.004 and P = 0.002, respectively). High levels of post-transplant IgA-anti-Fab antibody was more frequent in functioning-graft patients (P = 0.00001), correlated with decreased serum creatinine levels (P = 0.01) and associated with improved graft survival (P = 0.008). Our findings indicate the deleterious effect of early post-transplant HLA antibodies and increased sCD30 levels dependently and protective effect of IgA-anti-Fab antibodies on long-term renal graft outcomes. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time.

PubMed

Kumar, S K; Dispenzieri, A; Fraser, R; Mingwei, F; Akpek, G; Cornell, R; Kharfan-Dabaja, M; Freytes, C; Hashmi, S; Hildebrandt, G; Holmberg, L; Kyle, R; Lazarus, H; Lee, C; Mikhael, J; Nishihori, T; Tay, J; Usmani, S; Vesole, D; Vij, R; Wirk, B; Krishnan, A; Gasparetto, C; Mark, T; Nieto, Y; Hari, P; D'Souza, A

2018-04-01

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.

Pre-liver transplant psychosocial evaluation predicts post-transplantation outcomes.

PubMed

Benson, Ariel A; Rowe, Mina; Eid, Ahmad; Bluth, Keren; Merhav, Hadar; Khalaileh, Abed; Safadi, Rifaat

2018-08-01

Psychosocial factors greatly impact the course of patients throughout the liver transplantation process. A retrospective chart review was performed of patients who underwent liver transplantation at Hadassah-Hebrew University Medical Center between 2002 and 2012. A composite psychosocial score was computed based on the patient's pre-transplant evaluation. Patients were divided into two groups based on compliance, support and insight: Optimal psychosocial score and Non-optimal psychosocial score. Post-liver transplantation survival and complication rates were evaluated. Out of 100 patients who underwent liver transplantation at the Hadassah-Hebrew University Medical Center between 2002 and 2012, 93% had a complete pre-liver transplant psychosocial evaluation in the medical record performed by professional psychologists and social workers. Post-liver transplantation survival was significantly higher in the Optimal group (85%) as compared to the Non-optimal group (56%, p = .002). Post-liver transplantation rate of renal failure was significantly lower in the Optimal group. No significant differences were observed between the groups in other post-transplant complications. A patient's psychosocial status may impact outcomes following transplantation as inferior psychosocial grades were associated with lower overall survival and increased rates of complications. Pre-liver transplant psychosocial evaluations are an important tool to help predict survival following transplantation.

A Metabolomic Approach (1H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers.

PubMed

Vivot, Kevin; Benahmed, Malika A; Seyfritz, Elodie; Bietiger, William; Elbayed, Karim; Ruhland, Elisa; Langlois, Allan; Maillard, Elisa; Pinget, Michel; Jeandidier, Nathalie; Gies, Jean-Pierre; Namer, Izzie-Jacques; Sigrist, Séverine; Reix, Nathalie

2016-01-01

Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. 1 H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific. To study islet specific inflammatory events, immunohistochemistry was performed on sections of islet transplanted livers for thrombin (indicator of the instant blood-mediated inflammatory reaction (IBMIR)) and granulocytes and macrophages. We observed a specific correlation between IBMIR and granulocyte and macrophage infiltration after 12 h. In parallel, we identified a metabolic response associated with transplantation: after 12 h, glucose, alanine, aspartate, glutamate and glutathione were significantly increased. An increase of glucose is a marker of tissue degradation, and could be explained by immune cell infiltration. Alanine, aspartate and glutamate are inter-connected in a common metabolic pathway known to be activated during hypoxia. An increase of glutathione revealed the presence of antioxidant protection. In this study, IBMIR visualization combined with 1 H HRMAS NMR facilitated the characterization of cellular and molecular pathways recruited following islet transplantation.

A Metabolomic Approach (1H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers

PubMed Central

Vivot, Kevin; Benahmed, Malika A.; Seyfritz, Elodie; Bietiger, William; Elbayed, Karim; Ruhland, Elisa; Langlois, Allan; Maillard, Elisa; Pinget, Michel; Jeandidier, Nathalie; Gies, Jean-Pierre; Namer, Izzie-Jacques; Sigrist, Séverine; Reix, Nathalie

2016-01-01

Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. 1H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific. To study islet specific inflammatory events, immunohistochemistry was performed on sections of islet transplanted livers for thrombin (indicator of the instant blood-mediated inflammatory reaction (IBMIR)) and granulocytes and macrophages. We observed a specific correlation between IBMIR and granulocyte and macrophage infiltration after 12 h. In parallel, we identified a metabolic response associated with transplantation: after 12 h, glucose, alanine, aspartate, glutamate and glutathione were significantly increased. An increase of glucose is a marker of tissue degradation, and could be explained by immune cell infiltration. Alanine, aspartate and glutamate are inter-connected in a common metabolic pathway known to be activated during hypoxia. An increase of glutathione revealed the presence of antioxidant protection. In this study, IBMIR visualization combined with 1H HRMAS NMR facilitated the characterization of cellular and molecular pathways recruited following islet transplantation. PMID:27766032

Selective decontamination of the digestive tract helps prevent bacterial infections in the early postoperative period after liver transplant.

PubMed

Emre, S; Sebastian, A; Chodoff, L; Boccagni, P; Meyers, B; Sheiner, P A; Mor, E; Guy, S R; Atillasoy, E; Schwartz, M E; Miller, C M

1999-01-01

In liver transplant (LTx) recipients, gut-associated bacterial and fungal organisms produce significant postoperative morbidity and mortality. We sought to assess the role of selective digestive decontamination (SDD) in preventing postoperative infections in a large single-center cohort of liver recipients transplanted under two non-simultaneous protocols. In 212 consecutive patients transplanted between 1/1/91 and 7/31/92, SDD (gentamicin 80 mg, polymyxin B 100 mg, nystatin suspension 10 mL) was employed, starting after induction of anesthesia and continued until POD 21 (SDD Group). In 157 consecutive patients transplanted between 1/1/93 and 12/31/93, SDD was not used (non-SDD Group). Both groups received IV vancomycin and cefotaxime prophylaxis. All culture-positive infections within the first 30 days post-LTx were recorded and classified as bacterial or fungal. Infection-related mortality (patients who died of infectious complications without any technical complication) was recorded. Groups did not differ in patient demographics, United Network for Organ Sharing (UNOS) status, use of veno-venous bypass, total/warm ischemia, or length of ICU stay. Infections developed in fewer SDD patients (56/212; 26%) than non-SDD patients (69/157; 44%) (p<0.001). The incidence of gram-negative infection was less in the SDD group (11% vs. 26%, p<0. 001) as was gram-positive infection (16% vs. 26%, p<0.001). Among patients who developed infection, there was no difference between groups in infections per patient. Primary graft non-function (PNF) developed in 20 SDD patients (7/20 had infections) and 8 non-SDD patients (6/8 had infections) (p=0.06). There were no differences in incidence of fungal infections or of infection-related mortality between groups. In the SDD group, there were fewer abdominal (p<0. 001), lung (p<0.001), wound (p<0.01), and urinary tract infections (p<0.05). Use of SDD in liver recipients early after transplant was associated with significantly fewer

Causes of graft failure in simultaneous pancreas-kidney transplantation by various time periods.

PubMed

Wakil, Kayo; Sugawara, Yasuhiko; Kokudo, Norihiro; Kadowaki, Takashi

2013-01-01

Data collected by the United Network for Organ Sharing from all approved United States transplant programs was analyzed. The data included 26,572 adult diabetic patients who received a primary pancreas transplant between January 1987 and December 2012. Simultaneous pancreas-kidney (SPK) transplantation was the major therapeutic option for diabetes patients. SPK had better graft survival than pancreas transplant alone (PTA) or pancreas-after-kidney (PAK) or pancreas-with-kidney (from a living donor, PWK). The 5-year pancreas graft survival rates for SPK, PWK, PAK, and PTA were 70.0%, 57.2%, 54.0%, and 48.2%, respectively. When long-term SPK pancreas graft survival was examined by various transplant time periods, it was found that survival has remained almost stable since 1996. Graft survival rates were high among the pancreas recipients transplanted in the periods 1996-2000, 2001-2005, and 2006-2012, and the rates were similar: the 5-year rates were 68.9%, 72.4%, and 73.8%, respectively. Technical failure was the leading cause of graft loss during the first year post-transplant, regardless of period: 61.3%, 68.6%, 64.2%, and 71.9% for 1987-1995, 1996-2000, 2001-2005, and 2006-2012, respectively. After one year, chronic rejection was the leading cause of graft loss in all periods: 51.8%, 53.2%, 44.3%, and 40.7% for 1987-1995, 1996-2000, 2001-2005, and 2006-2012, respectively. Chronic rejection accounted for around 50% (or more) of the grafts that survived over five years. Survival of long-term pancreas grafts as well as long-term causes of graft loss remained almost unchanged across the different transplant periods. Clearly, there is a need for a means to identify early markers of chronic rejection, and to control it to improve long-term survival.

Incidence and early outcomes associated with pre-transplant antivimentin antibodies in the cardiac transplantation population.

PubMed

Young, Raymond K; Dale, Bethany; Russell, Stuart D; Zachary, Andrea A; Tedford, Ryan J

2015-08-01

In cardiac transplant recipients, the development of antibodies to the endothelial intermediate filament protein vimentin (antivimentin antibodies, AVA) has been associated with rejection and poor outcomes. However, the incidence of these antibodies prior to transplantation and their association with early rejection has not been investigated. Pre-transplant serum was analyzed from 50 patients who underwent de novo cardiac transplant at Johns Hopkins Hospital from 2004 to 2012. Demographic, one-yr rejection, and survival data were obtained from the transplant database. The incidence of pre-transplant AVA was 34%. AVA-positive patients were younger (p = 0.03), and there was an a trend toward incidence in females (p = 0.08). Demographic data were similar among both groups. AVA positivity did not predict rejection in the first year post-transplant. There was no difference in rejection-free graft survival (53 vs. 52%, p = 0.85) at one yr. Similarly, there was no difference in graft survival at one yr (82 vs. 88%, p = 0.56) or graft survival at a median follow-up of 23 and 26 months, respectively (76 vs. 85%, p = 0.41). AVA is common in the cardiac pre-transplant population with a higher incidence in the young. The presence of detectable AVA did not correlate with early post-transplant rejection or graft survival. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cutting-Balloon Angioplasty in Transplant Renal Artery Stenosis as First-Line Treatment in the Early Postoperative Period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ucar, Adem, E-mail: ucaradem@yahoo.com; Yahyayev, Aghakishi, E-mail: aghakishi@yahoo.com; Bakkaloglu, Huseyin, E-mail: drhuseyin@yahoo.com

2011-02-15

Percutaneous transluminal angioplasty has been successfully used for the treatment of transplant renal artery stenosis (RAS). Cutting-balloon angioplasty (CBA) is being used as a second option in pressure-resistant stenosis. It is thought that CBA is less traumatic and therefore restenosis occurs less frequently than in conventional angioplasty. This case report describes the unusual use of a cutting balloon in transplant RAS as a first option in the early postoperative period. Long-term follow-up data are also presented.

Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.

PubMed

Grenzi, Patricia C; Campos, Érika F; Silva, Hélio T; Felipe, Claudia R; Franco, Marcelo F; Soares, Maria F; Medina-Pestana, José O; Gerbase-DeLima, Maria

2015-03-01

Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

PubMed

Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

2009-01-01

Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

Increased risk of post-transplant malignancy and mortality in transplant tourists: a nationwide population-based cohort study in Taiwan.

PubMed

Chung, Mu-Chi; Wu, Ming-Ju; Chang, Chao-Hsiang; Muo, Chih-Hsin; Yu, Tung-Min; Ho, Hao-Chung; Shu, Kuo-Hsiung; Chung, Chi-Jung

2014-12-01

Information on post-transplant malignancy and mortality risk in kidney transplant tourists remains controversial and is an important concern. The present study aimed to evaluate the incidence of post-transplant malignancy and mortality risk between tourists and domestic transplant recipients using the claims data from Taiwan's universal health insurance. A retrospective study was performed on 2394 tourists and 1956 domestic recipients. Post-transplant malignancy and mortality were defined from the catastrophic illness patient registry by using the International Classification of Diseases, 9th Revision. Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. The incidence for post-transplant de novo malignancy in the tourist group was 1.8-fold higher than that of the domestic group (21.8 vs 12.1 per 1000 person-years). The overall cancer recurrence rate was approximately 11%. The top 3 post-transplant malignancies, in decreasing order, were urinary tract, kidney, and liver cancers, regardless of the recipient type. Compared with domestic recipients, there was significant higher mortality risk in transplant tourists (adjusted hazard ratio = 1.2, 95% confidence interval: 1.0-1.5). In addition, those with either pre-transplant or post-transplant malignancies were associated with increased mortality risk. We suggest that a sufficient waiting period for patients with pre-transplant malignancies should be better emphasized to eliminate recurrence, and transplant tourists should be discouraged because of the possibility of higher post-transplant de novo malignancy occurrence and mortality.

Clinical Characteristics of Monomorphic Post-transplant Lymphoproliferative Disorders

PubMed Central

Park, Byeong-Bae; Suh, Cheolwon; Won, Jong-Ho; Lee, Won-Sik; Shin, Ho-Jin

2010-01-01

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative disorders associated with immunosuppression and Epstein-Barr virus infection. PTLD is classified into three major categories: early lesions, polymorphic PTLD, and monomorphic PTLD. The majority of monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. This retrospective study was conducted to investigate the incidence, clinical manifestation, treatment, and outcomes of monomorphic PTLD among 5,817 recipients of solid organ or allogeneic hematopoietic stem cell transplantation from five institutions. Fourteen patients with monomorphic PTLD were identified (male:female 11:3; median age 42.6 yr, range 24-60). The overall incidence rate was 0.24%. The most common disease type was diffuse large B cell lymphoma (n=7). The median time between the transplant and diagnosis of PTLD was 85.8 months. However, all cases of PTLD after allogeneic hematopoietic stem cell transplantation occurred within 1 yr after transplantation. Ten of the 14 patients had EBV-positive tumor. Fourteen patients received combination systemic chemotherapy and four patients were treated with radiation therapy. Ten patients achieved a complete response (CR) and two patients a partial response (PR). The median follow-up period for surviving patients was 36.6 months. Nine patients remain alive (eight CR, one PR). Nine of 11 solid organ transplantations preserved graft function. The present study indicates a lower incidence rate and a longer median time before the development of PTLD than those of previous reports. Careful monitoring was needed after allogeneic hematopoietic stem cell transplantation for PTLD. PMID:20357991

Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

PubMed

Hernández-Méndez, Erick Alejandro; Arreola-Guerra, José Manuel; Morales-Buenrostro, Luis E; Ramírez, Julia B; Calleja, Said; Castelán, Natalia; Salcedo, Isaac; Vilatobá, Mario; Contreras, Alan G; Gabilondo, Bernardo; Granados, Julio; Alberú, Josefina

2014-01-01

Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.

In vivo intratumoral Epstein-Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications.

PubMed

Gonzalez-Farre, Blanca; Rovira, Jordina; Martinez, Daniel; Valera, Alexandra; Garcia-Herrera, Adriana; Marcos, Maria Angeles; Sole, Carla; Roue, Gael; Colomer, Dolors; Gonzalvo, Elena; Ribera-Cortada, Imma; Araya, Monica; Lloreta, Josep; Colomo, Luis; Campo, Elias; Lopez-Guillermo, Armando; Martinez, Antonio

2014-12-01

Post-transplant lymphoproliferative disorders are life-threatening complications following hematopoietic or solid organ transplantation. They represent a spectrum of mostly EBV-driven lymphoplasmacytic proliferations. While the oncogenic effect of EBV is related to latent infection, lytic infection also has a role in lymphomagenesis. In vitro, EBV replication is linked to plasma cell differentiation and XBP1 activation, although this phenomenon has never been addressed in vivo. We analyzed for the first time latent and lytic intratumoral EBV infection in a series of 35 adult patients with a diagnosis of post-transplant lymphoproliferative disorder (26M/9F, median age 54 years). A complete EBV study was performed including the analysis of the latent EBER, latent membrane protein-11, and EBV nuclear antigens as well as the immediate-early BZLF1/ZEBRA and early BMRF1/EADE31 lytic genes. XBP1 activation was assessed by nuclear protein expression. EBV infection was observed in 28 (80%) cases being latency II and III the most frequently observed 22 (79%). Intratumoral EBV replication was detected in 17 (60%) cases. Among these, XBP1 activation was observed in 11/12 evaluable cases associated with strong cytoplasmic immunoglobulin expression consistent with plasma cell differentiation. Intriguingly, the combination of latency III infection and EBV replication identified a high-risk subgroup of patients with significantly shorter survival (overall survival at 1 year 18% vs 48%) and early-onset (median of 7 vs 26 months) post-transplant lymphoproliferative disorder. Moreover, these patients appear to be more heavily immunosuppressed, so they exhibit lower rates of rejection and graft vs host disease but higher rates of cytomegalovirus reactivation. In conclusion, EBV replication is associated with plasma cell differentiation and XBP1 activation with prognostic implications. Both latency III and lytic EBV infection are related to aggressive and early-onset post-transplant

Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

PubMed

Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

2007-06-01

Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

INCIDENCE AND EARLY OUTCOMES ASSOCIATED WITH PRE-TRANSPLANT ANTI-VIMENTIN ANTIBODIES IN THE CARDIAC TRANSPLANTATION POPULATION

PubMed Central

Young, Raymond K.; Dale, Bethany; Russell, Stuart D.; Zachary, Andrea A.; Tedford, Ryan J.

2015-01-01

Background In cardiac transplant recipients, the development of antibodies to the endothelial intermediate filament protein vimentin (anti-vimentin antibodies, AVA) has been associated with rejection and poor outcomes. However, the incidence of these antibodies prior to transplantation and their association with early rejection has not been investigated. Methods Pre-transplant serum was analyzed from 50 patients who underwent de novo cardiac transplant at Johns Hopkins Hospital from 2004-2012. Demographic, one year rejection, and survival data were obtained from the transplant database. Results The incidence of pre-transplant AVA was 34%. AVA positive patients were younger (p=0.03) and there was an increased incidence in females (p=0.08). Demographic data were similar among both groups. AVA positivity did not predict rejection in the 1st year post-transplant. There was no difference in rejection-free graft survival (53 vs. 52%, p=0.85) at 1 year. Similarly there was no difference in graft survival at 1 year (82 vs. 88%, p=0.56) or graft survival at a median follow up of 23 and 26 months, respectively (76 vs. 85%, p=0.41). Conclusions AVA is common in the cardiac pre-transplant population with a higher incidence in the young. The presence of detectable AVA did not correlate with early post-transplant rejection or graft survival. PMID:25982351

[Early detection, prevention and management of renal failure in liver transplantation].

PubMed

Castells, Lluís; Baliellas, Carme; Bilbao, Itxarone; Cantarell, Carme; Cruzado, Josep Maria; Esforzado, Núria; García-Valdecasas, Juan Carlos; Lladó, Laura; Rimola, Antoni; Serón, Daniel; Oppenheimer, Federico

2014-10-01

Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Dual pathology as a cause of proteinuria in the post-transplant period; report of a case.

PubMed

Tewari, Rohit; Mendonca, Satish; Nijhawan, Vijay

2016-01-01

Proteinuria is common after renal transplantation and affects between 35%-45% of patients during the same year as their transplant. We report a case of dual pathology in the renal allograft as a cause of severe proteinuria. A 38-year-old male presented with end-stage renal disease. He underwent live related renal allograft transplant. His immediate post-transplant period was unremarkable. He developed rise in serum creatinine (2.1 mg/dl) 6 months after transplant and was biopsied. He was diagnosed as a case of acute cellular rejection type Ib with suspicion for antibody mediated rejection. He was treated with methylprednisolone to which he showed a good response with return of serum creatinine to 1.6 mg/dl. Subsequently, he developed a nephrotic range proteinuria 6 months after this episode of rejection. Repeat biopsy was performed. He was diagnosed as a case of immune complex mediated glomerulonephritis (GN) (morphologically consistent with pattern of membranoproliferative glomerulonephritis) with chronic humoral rejection in the form of transplant glomerulopathy (TG). IHC for C4d and immunofluorescence studies were instrumental making the diagnosis. He was treated with steroids and rituximab to which he showed a good response with remission of proteinuria. This case highlights the importance of picking up dual pathology in an allograft biopsy to ensure appropriate therapy. The role of C4d and its correct interpretation is further highlighted, especially with regard to pattern (granular versus linear) and location (glomerular capillaries versus peritubular capillaries).

Dual pathology as a cause of proteinuria in the post-transplant period; report of a case

PubMed Central

Tewari, Rohit; Mendonca, Satish; Nijhawan, Vijay

2016-01-01

Proteinuria is common after renal transplantation and affects between 35%-45% of patients during the same year as their transplant. We report a case of dual pathology in the renal allograft as a cause of severe proteinuria. A 38-year-old male presented with end-stage renal disease. He underwent live related renal allograft transplant. His immediate post-transplant period was unremarkable. He developed rise in serum creatinine (2.1 mg/dl) 6 months after transplant and was biopsied. He was diagnosed as a case of acute cellular rejection type Ib with suspicion for antibody mediated rejection. He was treated with methylprednisolone to which he showed a good response with return of serum creatinine to 1.6 mg/dl. Subsequently, he developed a nephrotic range proteinuria 6 months after this episode of rejection. Repeat biopsy was performed. He was diagnosed as a case of immune complex mediated glomerulonephritis (GN) (morphologically consistent with pattern of membranoproliferative glomerulonephritis) with chronic humoral rejection in the form of transplant glomerulopathy (TG). IHC for C4d and immunofluorescence studies were instrumental making the diagnosis. He was treated with steroids and rituximab to which he showed a good response with remission of proteinuria. This case highlights the importance of picking up dual pathology in an allograft biopsy to ensure appropriate therapy. The role of C4d and its correct interpretation is further highlighted, especially with regard to pattern (granular versus linear) and location (glomerular capillaries versus peritubular capillaries). PMID:28197503

Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match.

PubMed

Ohe, Hidenori; Waki, Kayo; Yoshitomi, Mami; Morimoto, Takeshi; Nafady-Hego, Hanaa; Satoda, Naoki; Li, Ying; Zhao, Xiangdong; Sakaguchi, Shimon; Uemoto, Shinji; Bishop, G Alex; Koshiba, Takaaki

2012-01-01

Pediatric recipients of living-donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi-allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post-Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr-tol), but not in 50 intolerant patients (Gr-intol). The Gr-intol consisted of 24 patients with rejection (Gr-rej) and 26 with fibrosis of grafts (Gr-fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11-7.02, P = 0.03], was a positive independent predictor, whereas HLA-A mismatch (0.18, 0.03-0.91, P = 0.04) was a negative predictor. HLA-DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr-intol (4.9%) compared with Gr-tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr-Tol (P = 0.02). Although HLA-B mismatch (8.73, 1.09-70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA-A match and the later predominance of Tregs are factors associated with OT. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

A critical analysis of early death after adult liver transplants.

PubMed

Rana, Abbas; Kaplan, Bruce; Jie, Tun; Porubsky, Marian; Habib, Shahid; Rilo, Horacio; Gruessner, Angelika C; Gruessner, Rainer W G

2013-01-01

The 15% mortality rate of liver transplant recipients at one yr may be viewed as a feat in comparison with the waiting list mortality, yet it nonetheless leaves room for much improvement. Our aim was to critically examine the mortality rates to identify high-risk periods and to incorporate cause of death into the analysis of post-transplant survival. We performed a retrospective analysis on United Network for Organ Sharing data for all adult recipients of liver transplants from January 1, 2002 to October 31, 2011. Our analysis included multivariate logistic regression where the primary outcome measure was patient death of 49,288 recipients. The highest mortality rate by day post-transplant was on day 0 (0.9%). The most significant risk factors were as follows: for one-d mortality from technical failure, intensive care unit admission odds ratio (OR 3.2); for one-d mortality from graft failure, warm ischemia >75 min (OR 5.6); for one-month mortality from infection, a previous transplant (OR 3.3); and for one-month mortality from graft failure, a previous transplant (OR 3.7). We found that the highest mortality rate after liver transplantation is within the first day and the first month post-transplant. Those two high-risk periods have common, as well as different, risk factors for mortality. © 2013 John Wiley & Sons A/S.

EARLY DIAGNOSIS IN POST RENAL TRANSPLANT OPPORTUNISTIC INFECTIONS: A FRESH LOOK.

PubMed

Chopra, G S; Narula, A S; Reddy, P S; Bhardwaj, J R

1999-04-01

A total of 86 renal transplant patients who were transplanted with live related donor (LRD) and live unrelated donor (LURD) kidneys were studied for opportunistic infections. Immune diagnosis of Toxoplasma, Cytomegalovirus (CMV), Herpes-simplex virus type II (HSV-2), Aspergillosis and Tuberculosis was carried out in these patients along with sputum examination, CSF studies and biopsy of lymphnode and other tissues in few cases. A high degree of Toxoplasma, CMV & HSV-2 positivity was seen in transplanted patients. However sensitivity of serological diagnosis of tuberculos was found to be low with standard criteria, which increased significantly when modified criteria were used. It is concluded that regular immunological monitoring should be carried out in transplanted patients so as to reach an early diagnosis and management of opportunistic infections.

Elevated fibroblast growth factor 23 levels as a cause of early post-renal transplantation hypophosphatemia.

PubMed

Han, S Y; Hwang, E A; Park, S B; Kim, H C; Kim, H T

2012-04-01

Hypophosphatemia is a common complication after renal transplantation. Hyperparathyroidism has long been thought to be the cause, but hypophosphatemia can persist after high parathyroid hormone (PTH) levels normalize. Furthermore, calcitriol levels remain inappropriately low after transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor 23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed prospective study to investigate if FGF-23 early after renal transplantation contributes to hypophosphatemia. We measured FGF-23 levels before and at 1, 2, 4, and 12 weeks after transplantation in 20 renal transplant recipients. Serum creatinine, calcium (Ca), phosphate (Pi), intact PTH (PTH), and 1,25-dihydroxy vitamin D (1,25(OH)(2)VitD) were measured at the same time. FGF-23 levels decreased by 97% at 4 weeks after renal transplantation (PRT) (7,471 ± 11,746 vs 225 ± 295 pg/mL; P < .05) but were still above normal. PTH and Pi levels also decreased significantly after renal transplantation, and Ca and 1,25(OH)(2)VitD slightly increased. PRT hypophosphatemia of <2.5 mg/dL developed in 15 (75%) and 12 (60%) patients at 4 weeks and 12 weeks respectively. Compared with nonhypophosphatemic patients, the levels of FGF-23 of hypophosphatemic patients were higher (303 ± 311 vs 10 ± 6.9 pg/mL; P = .02) at 4 weeks PRT. FGF-23 levels were inversely correlated with Pi (r(2) = 0.406; P = .011); PTH was not independently associated with Pi (r(2) = 0.132; P = .151). FGF-23 levels decrease dramatically after renal transplantation. During the early PRT period, Pi rapidly decreased, suggesting that FGF-23 is cleared by the kidney, but residual FGF-23 may contribute to the PRT hypophosphatemia. FGF-23, but not PTH levels, was independently associated with PRT hypophosphatemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Post-transplantation diabetes in kidney transplant recipients: an update on management and prevention.

PubMed

Conte, Caterina; Secchi, Antonio

2018-04-04

Post-transplantation diabetes mellitus (PTDM) may severely impact both short- and long-term outcomes of kidney transplant recipients in terms of graft and patient survival. However, PTDM often goes undiagnosed is underestimated or poorly managed. A diagnosis of PTDM should be delayed until the patient is on stable maintenance doses of immunosuppressive drugs, with stable kidney graft function and in the absence of acute infections. Risk factors for PTDM should be assessed during the pre-transplant evaluation period, in order to reduce the likelihood of developing diabetes. The oral glucose tolerance test is considered as the gold standard for diagnosing PTDM, whereas HbA1c is not reliable during the first months after transplantation. Glycaemic targets should be individualised, and comorbidities such as dyslipidaemia and hypertension should be treated with drugs that have the least possible impact on glucose metabolism, at doses that do not interact with immunosuppressants. While insulin is the preferred agent for treating inpatient hyperglycaemia in the immediate post-transplantation period, little evidence is available to guide therapeutic choices in the management of PTDM. Metformin and incretins may offer some advantage over other glucose-lowering agents, particularly with respect to risk of hypoglycaemia and weight gain. Tailoring immunosuppressive regimens may be of help, although maintenance of good kidney function should be prioritised over prevention/treatment of PTDM. The aim of this narrative review is to provide an overview of the available evidence on management and prevention of PTDM, with a focus on the available therapeutic options.

Post-Transplant Hypophosphatemia and the Risk of Death-Censored Graft Failure and Mortality after Kidney Transplantation.

PubMed

van Londen, Marco; Aarts, Brigitte M; Deetman, Petronella E; van der Weijden, Jessica; Eisenga, Michele F; Navis, Gerjan; Bakker, Stephan J L; de Borst, Martin H

2017-08-07

Hypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up. We performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center. We used a large real-life dataset containing 28,178 phosphate measurements (median of 27; first to third quartiles, 23-34) serial measurements per patient) and selected the lowest intraindividual phosphate level during the first year after transplantation. The primary outcomes were all-cause mortality, cardiovascular mortality, and death-censored graft failure. The median (interquartile range) intraindividual lowest phosphate level was 1.58 (1.30-1.95) mg/dl, and it was reached at 33 (21-51) days post-transplant. eGFR was the main correlate of the lowest serum phosphate level (model R 2 =0.32). During 9 (5-12) years of follow-up, 181 (19%) patients developed graft failure, and 295 (35%) patients died, of which 94 (32%) deaths were due to cardiovascular disease. In multivariable Cox regression analysis, more severe hypophosphatemia was associated with a lower risk of death-censored graft failure (fully adjusted hazard ratio, 0.61; 95% confidence interval, 0.43 to 0.88 per 1 mg/dl lower serum phosphate) and cardiovascular mortality (fully adjusted hazard ratio, 0.37; 95% confidence interval, 0.22 to 0.62) but not noncardiovascular mortality (fully adjusted hazard ratio, 1.33; 95% confidence interval, 0.9 to 1.96) or all-cause mortality (fully adjusted hazard ratio, 1.15; 95% confidence interval, 0.81 to 1.61). Post-transplant hypophosphatemia develops early after transplantation. These data connect post-transplant hypophosphatemia with favorable long-term graft and patient outcomes. Copyright © 2017 by the

Do mature forest birds prefer early-successional habitat during the post-fledging period?

Treesearch

Carlin C. Chandler; David I. King; Richard B. Chandler

2012-01-01

Recent studies have highlighted the importance of the post-fledging period to bird populations, suggesting that the importance of this portion of the life cycle is equal to or greater than the nesting period. Nevertheless, few studies have compared abundance of forest nesting species between mature forest and early-successional habitats while controlling for...

Patent foramen ovale does not have a negative impact on early outcomes in patients undergoing liver transplantation.

PubMed

Alba, Ana Carolina; Verocai Flaman, F; Granton, J; Delgado, D H

2011-01-01

To identify the impact of the presence of patent foramen ovale (PFO) in patients undergoing liver transplantation. Twenty-seven pre-liver transplant patients who had a PFO (PFO group) were identified and compared with 61 patients without PFO (NoPFO group). Patients were matched according to age, gender and cause of liver disease. The diagnosis of PFO was made by transthoracic echocardiography prior to liver transplantation. Patient baseline characteristics and complications during the early post-transplant period were analyzed. The mean age in the PFO group was 47 ± 14 (range 18-68) yr and 50 ± 11 (range 12-65) yr in the NoPFO group. The PFO group had a mean model for end-stage liver disease (MELD) score of 15 ± 10 whereas in the NoPFO group the MELD score was 19 ± 10 (p = 0.08). There were non-significant differences in echocardiographic parameters between groups. Duration of mechanical ventilation and the incidence of neurological complications were similar. Thirty-day mortality rate was similar in both groups; only one patient in the NoPFO group died within the first 30 days post-transplantation. The presence of PFO in patients with end-stage liver disease undergoing liver transplantation does not appear to affect patient outcomes during the peri-operative period. © 2010 John Wiley & Sons A/S.

Risk factors and clinical indicators for the development of biliary strictures post liver transplant: Significance of bilirubin

PubMed Central

Forrest, Elizabeth Ann; Reiling, Janske; Lipka, Geraldine; Fawcett, Jonathan

2017-01-01

AIM To identify risk factors associated with the formation of biliary strictures post liver transplantation over a period of 10-year in Queensland. METHODS Data on liver donors and recipients in Queensland between 2005 and 2014 was obtained from an electronic patient data system. In addition, intra-operative and post-operative characteristics were collected and a logistical regression analysis was performed to evaluate their association with the development of biliary strictures. RESULTS Of 296 liver transplants performed, 285 (96.3%) were from brain dead donors. Biliary strictures developed in 45 (15.2%) recipients. Anastomotic stricture formation (n = 25, 48.1%) was the commonest complication, with 14 (58.3%) of these occurred within 6-mo of transplant. A percutaneous approach or endoscopic retrograde cholangiography was used to treat 17 (37.8%) patients with biliary strictures. Biliary reconstruction was initially or ultimately required in 22 (48.9%) patients. In recipients developing biliary strictures, bilirubin was significantly increased within the first post-operative week (Day 7 total bilirubin 74 μmol/L vs 49 μmol/L, P = 0.012). In both univariate and multivariate regression analysis, Day 7 total bilirubin > 55 μmol/L was associated with the development of biliary stricture formation. In addition, hepatic artery thrombosis and primary sclerosing cholangitis were identified as independent risk factors. CONCLUSION In addition to known risk factors, bilirubin levels in the early post-operative period could be used as a clinical indicator for biliary stricture formation. PMID:29312864

Doppler ultrasonography in living donor liver transplantation recipients: Intra- and post-operative vascular complications

PubMed Central

Abdelaziz, Omar; Attia, Hussein

2016-01-01

Living-donor liver transplantation has provided a solution to the severe lack of cadaver grafts for the replacement of liver afflicted with end-stage cirrhosis, fulminant disease, or inborn errors of metabolism. Vascular complications remain the most serious complications and a common cause for graft failure after hepatic transplantation. Doppler ultrasound remains the primary radiological imaging modality for the diagnosis of such complications. This article presents a brief review of intra- and post-operative living donor liver transplantation anatomy and a synopsis of the role of ultrasonography and color Doppler in evaluating the graft vascular haemodynamics both during surgery and post-operatively in accurately defining the early vascular complications. Intra-operative ultrasonography of the liver graft provides the surgeon with useful real-time diagnostic and staging information that may result in an alteration in the planned surgical approach and corrections of surgical complications during the procedure of vascular anastomoses. The relevant intra-operative anatomy and the spectrum of normal and abnormal findings are described. Ultrasonography and color Doppler also provides the clinicians and surgeons early post-operative potential developmental complications that may occur during hospital stay. Early detection and thus early problem solving can make the difference between graft survival and failure. PMID:27468207

The lived experience of autologous stem cell-transplanted patients: Post-transplantation and before discharge.

PubMed

Alnasser, Qasem; Abu Kharmah, Salahel Deen; Attia, Manal; Aljafari, Akram; Agyekum, Felicia; Ahmed, Falak Aftab

2018-04-01

To explore the lived experience of the patients post-haematopoietic stem cell transplantation and specifically after engraftment and before discharge. Patients post-stem cell transplantation experience significant changes in all life aspects. Previous studies carried out by other researchers focused mainly on the postdischarge experience, where patients reported their perceptions that have always been affected by the life post-transplantation and influenced by their surroundings. The lived experience of patients, specifically after engraftment and prior to discharge (the "transition" phase), has not been adequately explored in the literature. Doing so might provide greater insight into the cause of change post-haematopoietic stem cell transplantation. This study is a phenomenological description of the participants' perception about their lived experience post-haematopoietic stem cell transplantation. The study used Giorgi's method of analysis. Through purposive sampling, 15 post-haematopoietic stem cell transplantation patients were recruited. Data were collected by individual interviews. Data were then analysed based on Giorgi's method of analysis to reveal the meaning of a phenomenon as experienced through the identification of essential themes. The analysis process revealed 12 core themes covered by four categories that detailed patients lived experience post-haematopoietic stem cell transplantation. The four categories were general transplant experience, effects of transplantation, factors of stress alleviation and finally life post-transplantation. This study showed how the haematopoietic stem cell transplantation affected the patients' physical, psychological and spiritual well-being. Transplantation also impacted on the patients' way of thinking and perception of life. Attending to patients' needs during transplantation might help to alleviate the severity of the effects and therefore improve experience. Comprehensive information about transplantation needs

Ventricular assist devices as bridge to heart transplantation: impact on post-transplant infections.

PubMed

Héquet, Delphine; Kralidis, Georg; Carrel, Thierry; Cusini, Alexia; Garzoni, Christian; Hullin, Roger; Meylan, Pascal R; Mohacsi, Paul; Mueller, Nicolas J; Ruschitzka, Frank; Tozzi, Piergiorgio; van Delden, Christian; Weisser, Maja; Wilhelm, Markus J; Pascual, Manuel; Manuel, Oriol

2016-07-08

Ventricular assist devices (VAD) are valuable options for patients with heart failure awaiting cardiac transplantation. We assessed the impact of pre-transplant VAD implantation on the incidence of post-transplant infections in a nationwide cohort of heart transplant recipients. Heart transplant recipients included in the Swiss Transplant Cohort Study between May 2008 and December 2012 were analyzed. Cumulative incidence curves were used to calculate the incidence of bacterial or Candida infections (primary endpoint) and of other infections (secondary endpoint) after transplant. Cox regression models treating death as a competing risk were used to identify risk factors for the development of infection after transplant. Overall, 119 patients were included in the study, 35 with a VAD and 84 without VAD. Cumulative incidences of post-transplant bacterial or Candida infections were 37.7 % in VAD patients and 40.4 % in non-VAD patients. In multivariate analysis, the use of cotrimoxazole prophylaxis was the only variable associated with bacterial/Candida infections after transplant (HR 0.29 [95 % CI 0.15-0.57], p < 0.001), but presence of a VAD was not (HR 0.94, [95 % CI 0.38-2.32], p = 0.89, for continuous-flow devices, and HR 0.45 [0.15 - 1.34], p = 0.15, for other devices). Risk for post-transplant viral and all fungal infections was not increased in patients with VAD. One-year survival was 82.9 % (29/35) in the VAD group and 82.1 % (69/84) in the non-VAD group. All 6 patients in the VAD group that died after transplant had a history of pre-transplant VAD infection. In this nationwide cohort of heart transplant recipients, the presence of VAD at the time of transplant had no influence on the development of post-transplant infections.

Regular monitoring of cytomegalovirus (CMV)-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment.

PubMed

Fernández-Ruiz, Mario; Giménez, Estela; Vinuesa, Víctor; Ruiz-Merlo, Tamara; Parra, Patricia; Amat, Paula; Montejo, Miguel; Paez-Vega, Aurora; Cantisán, Sara; Torre-Cisneros, Julián; Fortún, Jesús; Andrés, Amado; San Juan, Rafael; López-Medrano, Francisco; Navarro, David; María Aguado, José

2018-05-24

Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-center designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicenter cohort of intermediate-risk kidney transplant (KT) recipients. We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction preemptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4 + and CD8 + T-cells were enumerated through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and IE-1 peptides (mean of 6 measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T-cells were calculated at baseline and day 15. Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8 + T-cell count <1.0 cells/μL had higher risk of CMV events (adjusted hazard ratio [aHR]: 2.84; P-value = 0.054). When the CMI assessment was performed at the immediate post-transplant period (day 15), the presence of <2.0 CD8 + T-cells/μL (aHR: 2.18; P-value = 0.034) or <1.0 CD4 + T-cells/μL (aHR: 2.43; P-value = 0.016) also predicted the subsequent development of CMV event. In addition, lower counts of CMV-specific CD4 + (but not CD8 + ) T-cells at days 60 and 180 were associated with a higher incidence of late-onset events. Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Increased proximal acid reflux is associated with early readmission following lung transplantation.

PubMed

Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2016-02-01

Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed. This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring. Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis. Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered. © 2015 John Wiley & Sons Ltd.

Clinical evolution of post-transplant diabetes mellitus.

PubMed

Porrini, Esteban L; Díaz, Jose M; Moreso, Francisco; Delgado Mallén, Patricia I; Silva Torres, Irene; Ibernon, Meritxell; Bayés-Genís, Beatriz; Benitez-Ruiz, Rocío; Lampreabe, Ildefonso; Lauzurrica, Ricardo; Osorio, Jose M; Osuna, Antonio; Domínguez-Rollán, Rosa; Ruiz, Juan C; Jiménez-Sosa, Alejandro; González-Rinne, Ana; Marrero-Miranda, Domingo; Macía, Manuel; García, Javier; Torres, Armando

2016-03-01

The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Deconvoluting Post-Transplant Immunity: Cell Subset-Specific Mapping Reveals Pathways for Activation and Expansion of Memory T, Monocytes and B Cells

PubMed Central

Grigoryev, Yevgeniy A.; Kurian, Sunil M.; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L.; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M.; Kantor, Aaron B.; Marsh, Christopher; Salomon, Daniel R.

2010-01-01

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO+CD62L− effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant. PMID:20976225

Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.

PubMed

Grigoryev, Yevgeniy A; Kurian, Sunil M; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M; Kantor, Aaron B; Marsh, Christopher; Salomon, Daniel R

2010-10-14

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO(+)CD62L(-) effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant.

Volatile Biomarkers in Breath Associated With Liver Cirrhosis — Comparisons of Pre- and Post-liver Transplant Breath Samples

PubMed Central

Fernández del Río, R.; O'Hara, M.E.; Holt, A.; Pemberton, P.; Shah, T.; Whitehouse, T.; Mayhew, C.A.

2015-01-01

Background The burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics. Aims To determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful. Methods A two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period. Results Seven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics. Conclusions Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed. PMID:26501124

Pericardial constriction after cardiac transplantation.

PubMed

Bansal, Ramesh; Perez, Leandro; Razzouk, Anees; Wang, Nan; Bailey, Leonard

2010-03-01

In this study we present a series of 5 cases that developed constrictive pericarditis after orthotopic heart transplantation. All 5 patients had pericardial effusion of non-infectious etiology in the early post-transplant period. They subsequently presented with heart failure unresponsive to standard medical management. The diagnosis was made by comprehensive echo-Doppler studies. Findings were confirmed at surgical inspection and complete pericardiectomy led to improvement in hemodynamics in 4 patients. One patient had relief from constriction but died of non-cardiac complications. One patient with constriction has been re-listed for transplantation due to intermittent heart block and associated cardiac allograft vasculopathy. Early diagnosis of pericardial constriction after orthotopic heart transplantation requires a high index of clinical suspicion and optimal use of Doppler echocardiography. Early diagnosis and timely surgical pericardiectomy may correct this condition entirely and result in satisfactory long-term results.

Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile.

PubMed

Kumar, Ranjit; Maynard, Craig L; Eipers, Peter; Goldsmith, Kelly T; Ptacek, Travis; Grubbs, J Aaron; Dixon, Paula; Howard, Donna; Crossman, David K; Crowley, Michael R; Benjamin, William H; Lefkowitz, Elliot J; Weaver, Casey T; Rodriguez, J Martin; Morrow, Casey D

2016-01-13

Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice. A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%. We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early

Can zero-hour cortical biopsy predict early graft outcomes after living donor renal transplantation?

PubMed

Rathore, Ranjeet Singh; Mehta, Nisarg; Mehta, Sony Bhaskar; Babu, Manas; Bansal, Devesh; Pillai, Biju S; Sam, Mohan P; Krishnamoorthy, Hariharan

2017-11-01

The aim of this study was to identify relevance of subclinical pathological findings in the kidneys of living donors and correlate these with early graft renal function. This was a prospective study on 84 living donor kidney transplant recipients over a period of two years. In all the donors, cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial, and tubule status. The graft function of patients with normal histology was compared with those of abnormal histological findings at one, three, and six months, and one year post-surgery. Most abnormal histological findings were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF, 13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the commonly observed pathological findings in zero-hour biopsies. Only those donors who had histological changes of IF and ATN showed progressive deterioration of renal function at one month, three months, six months, and one year post-transplantation. In donors with other histological changes, no significant effect on graft function was observed. Zero-hour cortical biopsy gave us an idea of the general status of the donor kidney and presence or absence of subclinical pathological lesions. A mild degree of subclinical and pathological findings on zero-hour biopsy did not affect early graft renal function in living donor kidney transplantation. Zero-hour cortical biopsy could also help in discriminating donor-derived lesions from de novo alterations in the kidney that could happen subsequently.

Post-transplantation Development of Food Allergies.

PubMed

Newman, Erik N; Firszt, Rafael

2018-01-29

The development of food allergies is increasingly being recognized as a post-solid organ transplant complication. In this article, we review the spectrum of post-transplant food allergy development and the proposed mechanisms for de novo food allergies and the clinical significance they pose. The development of new food allergies is disproportionately associated with pediatric liver transplants, where it occurs in up to 38% of select populations. The mechanism of food allergy development is not completely understood; however, it is likely promoted by unbalanced immune suppression. De novo food allergy development is a common complication of solid organ transplants with the highest risk occurring in pediatric liver transplant recipients. There are likely multiple mechanisms for food allergy development including passive transfer of membrane-bound IgE and lymphocytes from donor to recipient, as well as loss of food tolerance and active development of new food allergies. The optimal management of food allergies following organ transplants has not been well researched but may include changing the immune suppression regimen if the food allergy does not resolve without intervention.

Imaging in lung transplants: Checklist for the radiologist.

PubMed

Madan, Rachna; Chansakul, Thanissara; Goldberg, Hilary J

2014-10-01

Post lung transplant complications can have overlapping clinical and imaging features, and hence, the time point at which they occur is a key distinguisher. Complications of lung transplantation may occur along a continuum in the immediate or longer postoperative period, including surgical and mechanical problems due to size mismatch and vascular as well as airway anastomotic complication, injuries from ischemia and reperfusion, acute and chronic rejection, pulmonary infections, and post-transplantation lymphoproliferative disorder. Life expectancy after lung transplantation has been limited primarily by chronic rejection and infection. Multiple detector computed tomography (MDCT) is critical for evaluation and early diagnosis of complications to enable selection of effective therapy and decrease morbidity and mortality among lung transplant recipients.

Psychosocial needs assessment post kidney transplant: Feasibility of a post-transplant specific support group.

PubMed

Brijmohan, Angela; Famure, Olusegun; Sihota, Kiren; Shea, Mary; Marzario, Barbara; Mitchell, Margot

2015-01-01

This project assessed unmet psychosocial needs of kidney transplant recipients and the feasibility of a support group located at an urban Canadian hospital to meet those needs. A survey assessed transplant recipient concerns about psychosocial issues related to transplantation, interest in a support group, desired group composition, facilitation, leadership, barriers and alternative forms of support. Most respondents were more than two years since transplant and were more concerned about medical complications, returning to normalcy, and had a greater desire to talk to other transplant recipients. Forty per cent of respondents indicated they would be interested in a support group. However, 60% indicated that a support group hosted in the hospital setting would be a deterrent to attending, citing time and transportation as the greatest barriers. More research is needed to assess the feasibility of post-kidney transplant support groups closer to recipients' homes and the feasibility of alternative forms of support.

Validation of a Simple Score to Determine Risk of Early Rejection After Pediatric Heart Transplantation.

PubMed

Butts, Ryan J; Savage, Andrew J; Atz, Andrew M; Heal, Elisabeth M; Burnette, Ali L; Kavarana, Minoo M; Bradley, Scott M; Chowdhury, Shahryar M

2015-09-01

This study aimed to develop a reliable and feasible score to assess the risk of rejection in pediatric heart transplantation recipients during the first post-transplant year. The first post-transplant year is the most likely time for rejection to occur in pediatric heart transplantation. Rejection during this period is associated with worse outcomes. The United Network for Organ Sharing database was queried for pediatric patients (age <18 years) who underwent isolated orthotopic heart transplantation from January 1, 2000 to December 31, 2012. Transplantations were divided into a derivation cohort (n = 2,686) and a validation (n = 509) cohort. The validation cohort was randomly selected from 20% of transplantations from 2005 to 2012. Covariates found to be associated with rejection (p < 0.2) were included in the initial multivariable logistic regression model. The final model was derived by including only variables independently associated with rejection. A risk score was then developed using relative magnitudes of the covariates' odds ratio. The score was then tested in the validation cohort. A 9-point risk score using 3 variables (age, cardiac diagnosis, and panel reactive antibody) was developed. Mean score in the derivation and validation cohorts were 4.5 ± 2.6 and 4.8 ± 2.7, respectively. A higher score was associated with an increased rate of rejection (score = 0, 10.6% in the validation cohort vs. score = 9, 40%; p < 0.01). In weighted regression analysis, the model-predicted risk of rejection correlated closely with the actual rates of rejection in the validation cohort (R(2) = 0.86; p < 0.01). The rejection score is accurate in determining the risk of early rejection in pediatric heart transplantation recipients. The score has the potential to be used in clinical practice to aid in determining the immunosuppressant regimen and the frequency of rejection surveillance in the first post-transplant year. Copyright © 2015 American College of Cardiology

Prevalence and risk factors for nonvertebral bone fractures in kidney transplant recipients - a single-center retrospective analysis.

PubMed

Jerman, Alexander; Lindič, Jelka; Škoberne, Andrej; Borštnar, Špela; Martinuč Bergoč, Maja; Godnov, Uroš; Kovač, Damjan

Complex and longstanding bone disease superimposed by harmful influences of immunosuppression is the reason for increased risk of bone fracture in kidney transplant recipients. The aim of our study was to analyze the incidence and prevalence of nonvertebral bone fractures and early (in the first post-transplant year) clinical and laboratory risk factors for suffering bone fracture in the long-term post-transplant period. Clinical and laboratory data as well as bone mineral density (BMD) measurements of 507 first kidney transplant recipients who were transplanted in the period from 1976 to 2011 were analyzed. The mean age of included patients was 54.3 ± 12.0 years, there were 45% females, and mean time on renal replacement treatment prior to transplantation was 63.4 ± 43.6 months. The average observation time post-transplant was 9.7 years (1.4 - 36.3 years). Post-transplant, 64 (12.6%) patients suffered 89 nonvertebral fractures (44 patients suffered 1 fracture, 15 patients 2 fractures, and 5 patients 3 fractures). Patients with fractures had significantly lower late BMD of femoral neck in the period of 1 - 10 years post-transplant, had osteopenia and osteoporosis more frequently in the same time period, and higher serum alkaline phosphatase in the first year post-transplant. 13 patients (13/64, 20.3%) had major fractures. Patients with major fractures were significantly older than patients with no major fractures and had lower serum albumin. Frequency of treatment with bisphosphonate, calcium, or phosphate did not differ between the groups. Vitamin D supplement (active form in 98% of cases) was prescribed more frequently in the group without fractures, but this was not statistically significant. Fracture rate in our transplant patient population was comparable to that reported in the literature. Except for a higher level of serum total alkaline phosphatase in the fracture group, we found no other early laboratory risk factors for bone fractures. BMD at

MELD score measured day 10 after orthotopic liver transplantation predicts death and re-transplantation within the first year.

PubMed

Rostved, Andreas A; Lundgren, Jens D; Hillingsø, Jens; Peters, Lars; Mocroft, Amanda; Rasmussen, Allan

2016-11-01

The impact of early allograft dysfunction on the outcome after liver transplantation is yet to be established. We explored the independent predictive value of the Model for End-Stage Liver Disease (MELD) score measured in the post-transplant period on the risk of mortality or re-transplantation. Retrospective cohort study on adults undergoing orthotopic deceased donor liver transplantation from 2004 to 2014. The MELD score was determined prior to transplantation and daily until 21 days after. The risk of mortality or re-transplantation within the first year was assessed according to quartiles of MELD using unadjusted and adjusted stepwise Cox regression analysis. We included 374 consecutive liver transplant recipients of whom 60 patients died or were re-transplanted. The pre-transplant MELD score was comparable between patients with good and poor outcome, but from day 1 the MELD score significantly diversified and was higher in the poor outcome group (MELD score quartile 4 versus quartile 1-3 at day 10: HR 5.1, 95% CI: 2.8-9.0). This association remained after adjustment for non-identical blood type, autoimmune liver disease and hepatocellular carcinoma (adjusted HR 5.3, 95% CI: 2.9-9.5 for MELD scores at day 10). The post-transplant MELD score was not associated with pre-transplant MELD score or the Eurotransplant donor risk index. Early determination of the MELD score as an indicator of early allograft dysfunction after liver transplantation was a strong independent predictor of mortality or re-transplantation and was not influenced by the quality of the donor, or preoperative recipient risk factors.

Total donor ischemic time: relationship to early hemodynamics and intensive care morbidity in pediatric cardiac transplant recipients.

PubMed

Rodrigues, Warren; Carr, Michelle; Ridout, Deborah; Carter, Katherine; Hulme, Sara Louise; Simmonds, Jacob; Elliott, Martin; Hoskote, Aparna; Burch, Michael; Brown, Kate L

2011-11-01

Single-center studies have failed to link modest increases in total donor ischemic time to mortality after pediatric orthotopic heart transplant. We aimed to investigate whether prolonged total donor ischemic time is linked to pediatric intensive care morbidity after orthotopic heart transplant. Retrospective cohort review. Tertiary pediatric transplant center in the United Kingdom. Ninety-three pediatric orthotopic heart transplants between 2002 and 2006. Total donor ischemic time was investigated for association with early post-orthotopic heart transplant hemodynamics and intensive care unit morbidities. Of 43 males and 50 females with median age 7.2 (interquartile range 2.2, 13.0) yrs, 62 (68%) had dilated cardiomyopathy, 20 (22%) had congenital heart disease, and nine (10%) had restrictive cardiomyopathy. The mean total donor ischemic time was 225.9 (sd 65.6) mins. In the first 24 hrs after orthotopic heart transplant, age-adjusted mean arterial blood pressure increased (p < .001), mean pulmonary arterial pressure fell (p = .012), but central venous pressure (p = .58) and left atrial pressure (p = .20) were unchanged. After adjustment for age, primary diagnosis, pre-orthotopic heart transplant mechanical support, and marginal donor factors, longer total donor ischemic time was significantly associated with lower mean arterial blood pressure (p < .001) in the first 24 hrs after orthotopic heart transplant, longer post-orthotopic heart transplant mechanical ventilation (p = .03), longer post-orthotopic heart transplant stay in the intensive care unit (p = .004), and longer post-orthotopic heart transplant stay in hospital (p = .02). Total donor ischemic time was not related to levels of mean pulmonary arterial pressure (p = .62), left atrial pressure (p = .38), or central venous pressure (p = .76) early after orthotopic heart transplant. Prolonged total donor ischemic time has an adverse effect on the donor organ, contributing to lower mean arterial blood

Low pretransplant IgA level is associated with early post-lung transplant seromucous infection.

PubMed

Murthy, Sudish C; Avery, Robin K; Budev, Marie; Gupta, Sandeep; Pettersson, Gösta B; Nowicki, Edward R; Mehta, Atul; Chapman, Jeffrey T; Rajeswaran, Jeevanantham; Blackstone, Eugene H

2018-04-13

Infection is an important cause of morbidity and mortality after lung transplantation. Immunoglobulins are part of both seromucous (IgA) and serum (IgG) infection defense mechanisms. We therefore hypothesized that lower pretransplant IgA levels would be associated with more early post-lung transplant seromucous infections and greater mortality independent of IgG. From January 2000 to July 2010, 538 patients undergoing primary lung transplantation had pretransplant IgA (n = 429) and IgG (n = 488) measured as a clinical routine. Median IgA was 200 mg·dL -1 (2% < 70 mg·dL -1 , lower limit of normal); median IgG was 970 mg·dL -1 (5% < 600 mg·dL -1 ). Intensive microbiology review was used to categorize infections and their causative organisms within the first posttransplant year. In total, 397 seromucous infections were observed in 247 patients, most bacterial. Although IgA and IgG were moderately correlated (r = 0.5, P < .0001), low pretransplant IgA was a strong risk factor (P = .01) for seromucous infections, but pretransplant IgG was not (P ≥ .6). As pretransplant IgA levels fell below 200 mg·dL -1 , the risk of these posttransplant infections rose nearly linearly. Lower pretransplant levels of IgA were associated with greater posttransplant mortality to end of follow-up (P = .004), but pretransplant IgG was not (P ≥ .3). Low levels of preoperative IgA, an important immunoglobulin involved in mucosal immunologic defense, but not IgG, are associated with seromucous infections in the year after lung transplantation and increased follow-up mortality. It would appear prudent to identify patients with relative IgA deficiency at listing and to increase vigilance of monitoring for, and prophylaxis against, seromucous infection in this high-risk population. Copyright © 2018. Published by Elsevier Inc.

Effect of transplant center volume on post-transplant survival in patients listed for simultaneous liver and kidney transplantation

PubMed Central

Modi, Rohan M; Tumin, Dmitry; Kruger, Andrew J; Beal, Eliza W; Hayes, Don; Hanje, James; Michaels, Anthony J; Washburn, Kenneth; Conteh, Lanla F; Black, Sylvester M; Mumtaz, Khalid

2018-01-01

AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation (SLKT) and liver transplantation alone (LTA) in SLKT-listed patients. METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Post-transplant survival was evaluated using stratified Cox regression with interaction between transplant type (LTA vs SLKT) and center volume. RESULTS During the study period, 393 of 4580 patients (9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients (180/393, 46%) than SLKT recipients (1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio (HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction (HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed. CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes. PMID:29399287

Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

PubMed Central

Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

2016-01-01

Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

Avascular necrosis of the femoral head post heart-transplantation and steroid dosage.

PubMed

Foley-Nolan, D; Daly, C; Barry, C; Woods, A; Neligan, M; Coughlan, R J

1992-12-01

Avascular necrosis (avn) post heart-transplantation has been considered to be due to the high doses of steroids used to immunosuppress these patients in attempting to prevent transplant rejection. This study shows that avascular necrosis occurs even when low dose steroids regimes are used and demonstrates no significant correlation between steroid dosage and the development of avn. Patients with symptomatic avn benefit from early diagnosis and management of their condition in that the need for total joint arthroplasty can be prevented in many cases.

Early fundoplication is associated with slower decline in lung function after lung transplantation in patients with gastroesophageal reflux disease.

PubMed

Biswas Roy, Sreeja; Elnahas, Shaimaa; Serrone, Rosemarie; Haworth, Cassandra; Olson, Michael T; Kang, Paul; Smith, Michael A; Bremner, Ross M; Huang, Jasmine L

2018-06-01

Gastroesophageal reflux disease (GERD) is prevalent after lung transplantation. Fundoplication slows lung function decline in patients with GERD, but the optimal timing of fundoplication is unknown. We retrospectively reviewed patients who underwent fundoplication after lung transplantion at our center from April 2007 to July 2014. Patients were divided into 2 groups: early fundoplication (<6 months after lung transplantation) and late fundoplication (≥6 months after lung transplantation). Annual decline in percent predicted forced expiratory volume in 1 second (FEV 1 ) was analyzed. Of the 251 patients who underwent lung transplantation during the study period with available pH data, 86 (34.3%) underwent post-transplantation fundoplication for GERD. Thirty of 86 (34.9%) had early fundoplication and 56 of 86 (65.1%) had late fundoplication. Median time from lung transplantation to fundoplication was 4.6 months (interquartile range, 2.0-5.2) and 13.8 months (interquartile range, 9.0-16.1) for the early and late groups, respectively. The median DeMeester score was comparable between groups. One-, 3-, and 5-year actuarial survival rates in the early group were 90%, 70%, and 70%, respectively; in the late group, these rates were 91%, 66%, and 66% (log rank P = .60). Three- and 5-year percent predicted FEV 1 was lower in the late group by 8.9% (95% confidence interval, -30.2 to 12.38; P = .46) and 40.7% (95% confidence interval, -73.66 to -7.69; P = .019). A linear mixed model showed a 5.7% lower percent predicted FEV 1 over time in the late fundoplication group (P < .001). In this study, patients with early fundoplication had a higher FEV 1 5 years after lung transplantation. Early fundoplication might protect against GERD-induced lung damage in lung transplant recipients with GERD. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Early Bacterial Pneumonia After Hepatic Transplantation: Epidemiologic Profile.

PubMed

Prieto Amorin, J; Lopez, M; Rando, K; Castelli, J; Medina Presentado, J

2018-03-01

Postoperative pulmonary complications are major cause of morbidity and mortality in patients receiving liver transplantation (LT), particularly bacterial pneumonia occurring within the first 100 days after transplantation. Our aim in this study was to determine the incidence, microorganisms involved, associated factors, and morbidity of bacterial pneumonia presenting in the first 100 days posttransplant. We performed a cohort study in which patients receiving liver transplantation were included prospectively in our national database (Database of Infections in Transplantation of Solid Organs). The study period was from July 14, 2009 to July 24, 2015. One hundred six patients were transplanted during the 6-year period. We documented 9 bacterial pneumonia cases with an incidence of 8.5 per 100 patients; 2 patients had hospital-acquired pneumonia (HAP) and 7 had ventilator-associated pneumonia (VAP). In 4 of the 9 bacterial pneumonia cases, patients presented with bacteremia. Eleven microorganisms were isolated these 9 patients. Microbiologic diagnosis methods included 5 cases of alveolar bronchoalveolar lavage (BAL), 1 case of BAL and pleural fluid puncture, 1 case of pleural fluid puncture, and 1 case through sputum study. Of the 11 isolated organisms, 9 corresponded to Gram-negative bacilli (GNB): Klebsiella spp, n = 3; Acinetobacter baumannii, n = 4; Morganella morganii, n = 1; and Pseudomonas aeruginosa, n = 1. Regarding the resistance profile, 7 presented with a multiresistance profile (MDR) and extreme resistance (XDR). Univariate analysis identified the Model for End-Stage Liver Disease (MELD) pretransplant score as a factor associated with developing pneumonia (P < .001, 95% confidence interval [CI] 2.872-10.167), and early extubation, before 8 hours posttransplant, as a protective factor (P = .008; relative risk [RR] 0.124; 95% CI 0 .041-0.377). Hospital stay was longer in patients with pneumonia compared to those without pneumonia (P < .0001, 95% CI

Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

PubMed Central

Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

2016-01-01

We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

Impact of antiviral prophylaxis in adults Epstein-Barr Virus-seronegative kidney recipients on early and late post-transplantation lymphoproliferative disorder onset: a retrospective cohort study.

PubMed

Ville, Simon; Imbert-Marcille, Berthe-Marie; Coste-Burel, Marianne; Garandeau, Claire; Meurette, Aurélie; Cantarovitch, Diego; Giral, Magali; Hourmant, Maryvonne; Blancho, Gilles; Dantal, Jacques

2018-05-01

Post-transplantation lymphoproliferative disorder (PTLD) pathogenesis is related to EBV infection. Mismatch with the donor (EBV D+/R-) is the main risk factor for both early PTLD (<1 year post-transplantation) and late (>1 year). In these at-risk patients, the role of antiviral prophylaxis for preventing PTLD remains controversial. We analyzed the impact of antiviral drugs given to prevent CMV disease in a monocentric retrospective cohort of 73 adult kidney or kidney-pancreas EBV-seronegative recipients, transplanted between 01/01/2000 and 01/01/2016. Thirty-seven (50.7%, prophylaxis group) received (val-)aciclovir or (val-)ganciclovir for 3-6 months and 36 (49.3%, no-prophylaxis group) received no-prophylaxis. Mean follow-up was 69 ± 7.2 months in the prophylaxis group and 91 ± 10.3 months in the no-prophylaxis group. Monitoring of EBV PCR revealed that prophylaxis delayed primary infection at 100 days (43% vs. 84%, P = 0.02). Early PTLD incidence was not different between groups (4/37 vs. 4/36, P = 0.99). Concerning late events, EBV-related neoplasia incidence was significantly lower in treated patients among whom no cases were observed, while in the no-prophylaxis group 6 cases were reported (P = 0.02). Despite a weak level of evidence our study suggests that antiviral prophylaxis could prevent late onset PTLD. © 2017 Steunstichting ESOT.

Bacterial infections after pediatric heart transplantation: Epidemiology, risk factors and outcomes.

PubMed

Rostad, Christina A; Wehrheim, Karla; Kirklin, James K; Naftel, David; Pruitt, Elizabeth; Hoffman, Timothy M; L'Ecuyer, Thomas; Berkowitz, Katie; Mahle, William T; Scheel, Janet N

2017-09-01

Bacterial infections represent a major cause of morbidity and mortality in heart transplant recipients. However, data describing the epidemiology and outcomes of these infections in children are limited. We analyzed the Pediatric Heart Transplant Study database of patients transplanted between 1993 and 2014 to determine the etiologies, risk factors and outcomes of children with bacterial infections post-heart transplantation. Of 4,458 primary transplants in the database, there were 4,815 infections that required hospitalization or intravenous therapy, 2,047 (42.51%) of which were bacterial. The risk of bacterial infection was highest in the first month post-transplant, and the bloodstream was the most common site (24.82%). In the early post-transplant period (<30 days post-transplant), coagulase-negative staphylococci were the most common pathogens (16.97%), followed by Enterobacter sp (11.99%) and Pseudomonas sp (11.62%). In the late post-transplant period, community-acquired pathogens Streptococcus pneumoniae (6.27%) and Haemophilus influenzae (2.82%) were also commonly identified. Patients' characteristics independently associated with acquisition of bacterial infection included younger age (p < 0.0001) and ventilator (p < 0.0001) or extracorporeal membrane oxygenation (p = 0.03) use at time of transplant. Overall mortality post-bacterial infection was 33.78%, and previous cardiac surgery (p < 0.001) and multiple sites of infection (p = 0.004) were independent predictors of death. Bacteria were the most common causes of severe infections in pediatric heart transplant recipients and were associated with high mortality rates. The risk of acquiring a bacterial infection was highest in the first month post-transplant, and a large proportion of the infections were caused by multidrug-resistant pathogens. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Thoracic organ transplantation: laboratory methods.

PubMed

Patel, Jignesh K; Kobashigawa, Jon A

2013-01-01

Although great progress has been achieved in thoracic organ transplantation through the development of effective immunosuppression, there is still significant risk of rejection during the early post-transplant period, creating a need for routine monitoring for both acute antibody and cellular mediated rejection. The currently available multiplexed, microbead assays utilizing solubilized HLA antigens afford the capability of sensitive detection and identification of HLA and non-HLA specific antibodies. These assays are being used to assess the relative strength of donor specific antibodies; to permit performance of virtual crossmatches which can reduce the waiting time to transplantation; to monitor antibody levels during desensitization; and for heart transplants to monitor antibodies post-transplant. For cell mediated immune responses, the recent development of gene expression profiling has allowed noninvasive monitoring of heart transplant recipients yielding predictive values for acute cellular rejection. T cell immune monitoring in heart and lung transplant recipients has allowed individual tailoring of immunosuppression, particularly to minimize risk of infection. While the current antibody and cellular laboratory techniques have enhanced the ability to manage thoracic organ transplant recipients, future developments from improved understanding of microchimerism and graft tolerance may allow more refined allograft monitoring techniques.

Vaccination titres pre- and post-transplant in paediatric renal transplant recipients and the impact of immunosuppressive therapy.

PubMed

Höcker, Britta; Aguilar, Martin; Schnitzler, Paul; Pape, Lars; Bald, Martin; König, Jens; Marks, Stephen D; Genc, Gurkan; Büscher, Anja; Kemper, Markus J; Billing, Heiko; Pohl, Martin; Dello Strologo, Luca; Webb, Nicholas J A; Rieger, Susanne; Mankertz, Annette; Krupka, Kai; Bruckner, Thomas; Fichtner, Alexander; Tönshoff, Burkhard

2018-05-01

Avoidance of vaccine-preventable infections in paediatric renal allograft recipients is of utmost importance. However, the development and maintenance of protective vaccination titres may be impaired in this patient population owing to their need for immunosuppressive medication. In the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national study and analysed vaccination titres pre- and post-transplant in 155 patients with serial titre measurements in comparison with published data in healthy children. The percentage of patients with positive vaccination titres before renal transplantation (RTx) was low, especially for diphtheria (38.5%, control 75%) and pertussis (21.3%, control 96.3%). As few as 58.1% of patients had a hepatitis B antibody (HBsAb) titre >100 IU/L before RTx. 38.1% of patients showed a vaccination titre loss post-transplant. Patients with an HBsAb titre between 10 and 100 IU/L before RTx experienced a significantly (p < 0.05) more frequent hepatitis B vaccination titre loss post-transplant than patients with an HBsAb titre >100 IU/L. The revaccination rate post-transplant was low and revaccination failed to induce positive titres in a considerable number of patients (27.3 to 83.3%). Treatment with rituximab was associated with a significantly increased risk of a vaccination titre loss post-transplant (odds ratio 4.26, p = 0.033). These data show a low percentage of patients with positive vaccination titres pre-transplant, a low revaccination rate post-transplant with limited antibody response, and a high rate of vaccination titre losses.

Clinical Efficacy and Safety of Pamidronate Therapy on Bone Mass Density in Early Post-Renal Transplant Period: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Zijie; Han, Zhijian; Tao, Jun; Lu, Pei; Liu, Xuzhong; Wang, Jun; Wu, Bian; Huang, Zhengkai; Yin, Changjun; Tan, Ruoyun; Gu, Min

2014-01-01

Introduction The overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined. Materials and Methods A comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the “Cochrane Handbook for Systematic Reviews of Interventions 5.0.2” were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate. Results Six randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD)  = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD  = 3.53 [−1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD  = −3.101 [−5.33, −0.89]; serum calcium: SMD  = 2.18 [−0.8, 5.16]; serum iPTH: SMD  = 0.06 [−0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine. Conclusions This meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year.

PubMed

Grąt, Michał; Lewandowski, Zbigniew; Grąt, Karolina; Wronka, Karolina Maria; Krasnodębski, Maciej; Barski, Krzysztof; Zborowska, Hanna; Patkowski, Waldemar; Zieniewicz, Krzysztof; Krawczyk, Marek

2014-10-01

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long-term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655) but worse during the five subsequent years among the five-yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post-transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non-ALD recipients up to the fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative effects on post-transplant outcomes beyond the fifth post-transplant year, not attributable to recidivism. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Takotsubo cardiomyopathy post liver transplantation.

PubMed

Vachiat, Ahmed; McCutcheon, Keir; Mahomed, Adam; Schleicher, Gunter; Brand, Liezl; Botha, Jean; Sussman, Martin; Manga, Pravin

2016-10-23

A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.

Estimation of abbreviated mycophenolic acid area under the concentration-time curve during early posttransplant period by limited sampling strategy.

PubMed

Mohammadpour, A-H; Nazemian, F; Abtahi, B; Naghibi, M; Gholami, K; Rezaee, S; Nazari, M-R A; Rajabi, O

2008-12-01

Area under the concentration curve (AUC) of mycophenolic acid (MPA) could help to optimize therapeutic drug monitoring during the early post-renal transplant period. The aim of this study was to develop a limited sampling strategy to estimate an abbreviated MPA AUC within the first month after renal transplantation. In this study we selected 19 patients in the early posttransplant period with normal renal graft function (glomerular filtration rate > 70 mL/min). Plasma MPA concentrations were measured using reverse-phase high-performance liquid chromatography. MPA AUC(0-12h) was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal and convenient time points of MPA levels that could be used to derive model equations best fitted to MPA AUC(0-12h). The regression equation for AUC estimation that gave the best performance was AUC = 14.46 C(10) + 15.547 (r(2) = .882). The validation of the method was performed using the jackknife method. Mean prediction error of this model was not different from zero (P > .05) and had a high root mean square prediction error (8.06). In conclusion, this limited sampling strategy provided an effective approach for therapeutic drug monitoring during the early posttransplant period.

Quantifying the medication burden of kidney transplant recipients in the first year post-transplantation.

PubMed

Low, Jac Kee; Crawford, Kimberley; Manias, Elizabeth; Williams, Allison

2018-06-28

Background Kidney transplantation is an effective treatment, but it is not a cure. Since the risk of graft rejection and the presence of comorbid conditions remain for a lifetime, medications are necessary. Objective To examine the prescription medication burden of adult kidney transplant recipients from 3- to 12-months post-transplantation. Setting All five adult kidney transplant units in Victoria, Australia. Method As part of a larger intervention study, we conducet a retrospective review of prescription refill records and medical records containing the history of medication changes of 64 participants who completed the study was undertaken. The complexity of the medication management was studied, and we looked at the burden of maintaining the medications supply. Outcome measures Pill burden, administration frequency, dose changes frequency, immunosuppressive medication changes, the estimated out-of-pocket costs of medications and frequency of pharmacy visits. Results At 3 months, the average daily pill burden was 22 (SD = 9) whilst at 12 months, it was 23 (SD = 10). Some participants required long-term prophylaxis of fungal infections up to 4 times a day whilst those with diabetes had to manage up to 4 insulin doses a day. The average out-of-pocket cost per person and the frequency of pharmacy visits at 6, 9 and 12 months post-transplantation remained relatively unchanged. Conclusion The medication regimen prescribed for kidney transplant recipients is complex and for most patients, it did not simplify over time post transplantation. Strategies are needed to support patients in managing the complexity of their medication regimen following kidney transplantation.

Pre-Kidney Transplant Lower Extremity Impairment and Post-Kidney Transplant Mortality.

PubMed

Nastasi, A J; McAdams-DeMarco, M A; Schrack, J; Ying, H; Olorundare, I; Warsame, F; Mountford, A; Haugen, C E; González Fernández, M; Norman, S P; Segev, D L

2018-01-01

Prediction models for post-kidney transplantation mortality have had limited success (C-statistics ≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, consequently, kidney transplant (KT) survival through intervention. The Short Physical Performance Battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0-4, for a composite score of 0-12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009 to 6/2016) and University of Michigan (2/2013 to 12/2016). The independent associations between SPPB impairment (SPPB composite score ≤10) and composite score with post-KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5-year posttransplantation mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (p < 0.001). Impaired recipients had a 2.30-fold (adjusted hazard ratio [aHR] 2.30, 95% confidence interval [CI] 1.12-4.74, p = 0.02) increased risk of postkidney transplantation mortality compared to unimpaired recipients. Each one-point decrease in SPPB score was independently associated with a 1.19-fold (95% CI 1.09-1.30, p < 0.001) higher risk of post-KT mortality. SPPB-derived lower extremity function is a potentially highly useful and modifiable objective measure for pre-KT risk prediction. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Pulmonary rehabilitation in lung transplant candidates.

PubMed

Li, Melinda; Mathur, Sunita; Chowdhury, Noori A; Helm, Denise; Singer, Lianne G

2013-06-01

While awaiting lung transplantation, candidates may participate in pulmonary rehabilitation to improve their fitness for surgery. However, pulmonary rehabilitation outcomes have not been systematically evaluated in lung transplant candidates. This investigation was a retrospective cohort study of 345 pre-transplant pulmonary rehabilitation participants who received a lung transplant between January 2004 and June 2009 and had available pre-transplant exercise data. Data extracted included: 6-minute walk tests at standard intervals; exercise training details; health-related quality-of-life (HRQL) measures; and early post-transplant outcomes. Paired t-tests were used to examine changes in the 6MW distance (6MWD), exercise training volume and HRQL during the pre-transplant period. We evaluated the association between pre-transplant 6MWD and transplant hospitalization outcomes. The final 6MWD prior to transplantation was only 15 m less than the listing 6MWD (n = 200; p = 0.002). Exercise training volumes increased slightly from the start of the pulmonary rehabilitation program until transplant: treadmill, increase 0.69 ml/kg/min (n = 238; p < 0.0001); biceps resistance training, 18 lbs. × reps (n = 286; p < 0.0001); and quadriceps resistance training, 15 lbs. × reps (n = 278; p < 0.0001). HRQL measures declined. A greater final 6MWD prior to transplant correlated with a shorter length of stay in the hospital (n = 207; p = 0.003). Exercise capacity and training volumes are well preserved among lung transplant candidates participating in pulmonary rehabilitation, even in the setting of severe, progressive lung disease. Participants with greater exercise capacity prior to transplantation have more favorable early post-transplant outcomes. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Peritoneal Dialysis Catheter Removal Post-Transplant - A Rare Case of Delayed Bowel Perforation.

PubMed

Maxted, Andrew P; Davies, Brian; Colliver, Daniel; Williams, Alun; Lunn, Andrew

2017-01-01

Peritoneal dialysis (PD) is a well-established form of renal replacement therapy and the practice of leaving catheters in situ post-transplantation widely accepted. We present a rare complication: a child presenting with anal protrusion of the PD catheter.The patient is an 11-year-old boy with a background of renal dysplasia and congenital cutis laxa. Twenty-three weeks after dialysis was commenced, the patient underwent a renal transplant. Thirteen weeks post-transplant, the patient felt an unusual sensation after defecation. The curled end of the catheter was seen protruding from the anus. He was admitted, and investigations showed stable graft function, with abdominal X ray showing no free air.Intraoperative findings showed a small perforation of the sigmoid colon sealed off by adherence of several small intestinal loops. This was repaired laparoscopically after removal of the distal part of the catheter per rectum. No peritoneal contamination was seen. He was treated with 5 days of intravenous antibiotics and gradual introduction of enteral feeds. His graft function remained stable throughout.Timing of catheter removal varies, from the time of transplantation to over 3 months post-transplantation. Bowel perforation due to PD catheter insertion is rare and tends to occur at the time of insertion. Anal protrusion of a PD catheter in childhood is extremely rare and unrecorded in a pediatric patient with a connective tissue disorder. Our case highlights that serious complications can occur in the period between transplantation and elective PD catheter removal and that, in the immunocompromised patient, signs can be subtle. Copyright © 2017 International Society for Peritoneal Dialysis.

Planar xanthomas secondary to post-transplantation cholangiopathy in a 16-month-old boy.

PubMed

Patel, Nirali; Norberg, Adam; Hogeling, Marcia

2018-05-01

Planar xanthomas in children represent rare dermatologic findings associated with abnormalities in lipid metabolism. While planar xanthomas in Alagille's syndrome have been well described in the literature, there have been no cases reported of eruptive xanthomas in pediatric liver transplant patients. Herein we report a case of a 16-month-old boy status post-liver transplantation who presents with planar xanthomas secondary to cholangiopathy. A brief review of xanthomas and the related literature is also provided. © 2018 Wiley Periodicals, Inc.

Cardiovascular disease in live related renal transplantation.

PubMed

Kaul, A; Sharm, R K; Gupta, A; Sinha, N; Singh, U

2011-11-01

Cardiovascular disease has become the leading cause of morbidity and mortality in renal transplant recipients, although its pathogenesis and treatment are poorly understood. Modifiable cardiovascular risk factors and graft dysfunction both play an important role in development of post transplant cardiovascular events. Prevalence of cardiovascular disease was studied in stable kidney transplant patients on cyclosporine based triple immunosuppression in relation to the various risk factors and post transplant cardiovascular events. Analysis of 562 post transplant patients with stable graft function for 6 months, the patients were evaluated for cardiovascular events in post transplant period. Pre and post transplant risk factors were analyzed using the COX proportional hazard model. 174 patients had undergone pre transplant coronary angiography, 15 of these patients underwent coronary revascularization (angioplasty in 12, CABG in 3). The prevalence of CAD was 7.2% in transplant recipients. Of 42 patients with CAD 31 (73.8%) had cardiovascular event in post transplant period. Age > or = 40 yrs, male sex, graft dysfunction, diabetes as primary renal disease, pre transplant cardiovascular event, chronic rejection showed significant correlation in univariate analysis and there was significant between age > or = 40 years (OR = 2.16 with 95% CI, 0.977-4.78) S creatinine > or = 1.4 mg % (OR = 2.40 with 95% CI, 1.20 - 4.82), diabetes as primary disease (OR with 95% CI 3.67, 3.2-14.82), PTDM (OR 3.67, 95% CI 1.45-9.40), pre-transplant cardiovascular disease (OR 4.14, 95% CI .38-13.15) with post transplant cardiovascular event on multivariate analysis. There was poor patient and graft survival among those who suffered post transplant cardiovascular event. The incidence of cardiovascular disease continues to be high after renal transplantation and modifiable risk factors should be identified to prevent occurrence of events in post transplant period.

Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants

PubMed Central

Potluri, Vishnu S.; Hall, Isaac E.; Ficek, Joseph; Doshi, Mona D.; Butrymowicz, Isabel; Weng, Francis L.; Schröppel, Bernd; Thiessen-Philbrook, Heather; Reese, Peter P.

2016-01-01

Background and objectives Data reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post–transplant outcome measures is unknown. Design, setting, participants, & measurements The Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post–transplant week), acute rejection, and post–transplant serum creatinine reported to the OPTN with data collected for the DDS. Results Median kidney donor risk index was 1.22 (interquartile range [IQR], 0.97–1.53). Median recipient age was 55 (IQR, 46–63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%–100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92). Conclusions OPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft

Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

ClinicalTrials.gov

2017-02-07

Chronic Allograft Nephropathy; Chronic Kidney Disease; Chronic Renal Failure; Disordered Mineral Metabolism; End Stage Renal Disease; Hyperparathyroidism; Hypophosphatemia; Kidney Disease; Kidney Transplantation; Post Renal Transplantation

Early lung retrieval from traumatic brain-dead donors does not compromise outcomes following lung transplantation.

PubMed

Moreno, Paula; Alvarez, Antonio; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Cerezo, Francisco; Algar, Francisco Javier; Salvatierra, Angel

2013-06-01

To determine whether lung retrieval from traumatic donors performed within 24 h of brain death has a negative impact on early graft function and survival after lung transplantation (LT), when compared with those retrieved after 24 h. Review of lung transplants performed from traumatic donors over a 17-year period. Recipients were distributed into two groups: transplants from traumatic donor lungs retrieved within 24 h of brain death (Group A), and transplants from traumatic donor lungs retrieved after 24 h of brain death (Group B). Demographic data of donors and recipients, early graft function, perioperative complications and mortality were compared between both groups. Among 356 lung transplants performed at our institution, 132 were from traumatic donors (70% male, 30% female). Group A: 73 (55%); Group B: 59 (45%). There were 53 single, 77 double, and 2 combined LT. Indications were emphysema in 41 (31%), pulmonary fibrosis in 31 (23%), cystic fibrosis in 38 (29%), bronchiectasis in 9 (7%) and other indications in 13 patients (10%). Donor and recipient demographic data, need or cardiopulmonary bypass, postoperative complications and Intensive Care Unit and hospital stay did not differ between groups. Primary graft dysfunction (A vs B): 9 (16%) vs 13 (26%) P = 0.17. PaO2/FiO2 24 h post-transplant (A vs B): 303 mmHg vs 288 mmHg (P = 0.57). Number of acute rejection episodes (A vs B): 0.93 vs 1.49 (P = 0.01). Postoperative intubation time (A vs B): 99 vs 100 h (P = 0.99). 30-day mortality (A vs B): 7 (10%) vs 2 (3.5%) (P = 0.13). Freedom from bronchiolitis obliterans syndrome (A vs B): 82, 72, 37, 22 vs 78, 68, 42, 15%, at 3, 5, 10 and 15 years, respectively (P = 0.889). Survival (A vs B): 65, 54, 46, 42 and 27 vs 60, 50, 45, 43 and 29% at 3, 5, 7, 10 and 15 years, respectively (P = 0.937). In our experience, early lung retrieval after brain death from traumatic donors does not adversely affect early and long-term outcomes after LT.

Change of sleep quality from pre- to 3 years post-solid organ transplantation: The Swiss Transplant Cohort Study

PubMed Central

Denhaerynck, Kris; Huynh-Do, Uyen; Binet, Isabelle; Hadaya, Karine; De Geest, Sabina

2017-01-01

Background Poor sleep quality (SQ) is common after solid organ transplantation; however, very little is known about its natural history. We assessed the changes in SQ from pre- to 3 years post-transplant in adult heart, kidney, liver and lung recipients included in the prospective nation-wide Swiss Transplant Cohort Study. We explored associations with selected variables in patients suffering persistent poor SQ compared to those with good or variable SQ. Methods Adult single organ transplant recipients enrolled in the Swiss Transplant Cohort Study with pre-transplant and at least 3 post-transplant SQ assessment data were included. SQ was self-reported pre-transplant (at listing), then at 6, 12, 24 and 36 months post-transplant. A single SQ item was used to identify poor (0–5) and good sleepers (6–10). Between organ groups, SQ was compared via logistic regression analysis with generalized estimating equations. Within the group reporting persistently poor SQ, we used logistic regression or Kaplan-Meier analysis as appropriate to check for differences in global quality of life and survival. Results In a sample of 1173 transplant patients (age: 52.1±13.2 years; 65% males; 66% kidney, 17% liver, 10% lung, 7% heart) transplanted between 2008 and 2012, pre- transplant poor SQ was highest in liver (50%) and heart (49%) recipients. Overall, poor SQ decreased significantly from pre-transplant (38%) to 24 months post-transplant (26%) and remained stable at 3 years (29%). Patients reporting persistently poor SQ had significantly more depressive symptomatology and lower global quality of life. Conclusion Because self-reported poor SQ is related to poorer global quality of life, these results emphasize the need for further studies to find suitable treatment options for poor SQ in transplant recipients. PMID:29020112

Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

PubMed

Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

2018-05-18

Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

What can happen after lung transplantation and the importance of the time since transplantation: radiological review of post-transplantation complications.

PubMed

Daimiel Naranjo, I; Alonso Charterina, S

2016-01-01

Lung transplantation is the best treatment option in the final stages of diseases such as cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis. Better surgical techniques and advances in immunosuppressor treatments have increased survival in lung transplant recipients, making longer follow-up necessary because complications can occur at any time after transplantation. For practical purposes, complications can be classified as early (those that normally occur within two months after transplantation), late (those that normally occur more than two months after transplantation), or time-independent (those that can occur at any time after transplantation). Many complications have nonspecific clinical and radiological manifestations, so the time factor is key to narrow the differential diagnosis. Imaging can guide interventional procedures and can detect complications early. This article aims to describe and illustrate the complications that can occur after lung transplantation from the clinical and radiological viewpoints so that they can be detected as early as possible. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Challenges in transplantation for alcoholic liver disease.

PubMed

Berlakovich, Gabriela A

2014-07-07

Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

Relative reductions in soluble CD30 levels post-transplant predict acute graft function in islet allograft recipients receiving three different immunosuppression protocols.

PubMed

Hire, Kelly; Hering, Bernhard; Bansal-Pakala, Pratima

2010-08-01

Despite advances in islet transplantation, challenges remain in monitoring for anti-islet immune responses. Soluble CD30 (sCD30) has been investigated as a predictor of acute rejection in kidney, lung, and heart transplantation as well as in a single study in human islet cell recipients. In this study, sCD30 levels were retrospectively assessed in 19 allograft recipients treated with three different immunosuppression induction therapies. Soluble CD30 levels were assessed at pre-transplant; early post-transplant (day 4-day 7); one-month post-transplant; and late post-transplant (day 90-day 120) and then correlated with eventual graft outcomes at 1-year follow-up. Results showed no correlation between mean serum sCD30 levels at any point in time pre- or post-transplant and graft function at 1-year follow-up. However, analysis demonstrated that mean sCD30 levels at day 28 or day 90-day 120 decreased from pre-transplant levels in recipients with long-term islet allograft function compared to recipients with partial or non-graft function (a decrease of 43.6+/-25.6% compared to 16.7+/-35.2%, p<0.05). In another finding, immunosuppression with the ATG protocol led to a greater reduction in sCD30 levels post-transplant overall. A larger reduction post-transplant correlated with full graft function. The results demonstrate that a relative reduction in sCD30 levels post-transplant may be applicable as a biomarker to monitor graft function in islet allograft recipients. Additionally, knowledge of the impact of various immunosuppression protocols on the timing and extent of changes in post-transplant sCD30 levels could aid in patient-specific tailoring of immunosuppression. Copyright © 2010 Elsevier B.V. All rights reserved.

First two decades of paediatric heart transplantation in Sweden - outcome of listing and post-transplant results.

PubMed

Gilljam, Thomas; Higgins, Thomas; Bennhagen, Rolf; Wåhlander, Håkan

2011-11-01

To evaluate outcome in the first generation of children with end-stage heart disease to whom heart transplantation was available. Retrospective review of all 135 Swedish children <18 years old listed for heart transplantation 1989-2009, followed to December 31, 2009, including 74 (55%) with cardiomyopathy and 61 (45%) with congenital heart disease; 34 (25%) were infants (<1 year). Cumulative risk of requiring heart transplantation was 1:17,300 (11 patients who improved were omitted from outcome analysis). Waiting-list mortality was 31% (44% in infants). Median waiting time in 82 transplanted patients was 57 days (0-585 days). Post-transplant follow-up time was median 5.9 years (0.03-20.1 years), and actuarial survival was 92% at 1 year, 82% at 5 years, 76% at 10 years and 58% at 15 years. Survival after listing was 64% at 1 year, 58% at 5 years, 52% at 10 years and 40% at 15 years. Post-transplant complications included rejections (34%), malignancies (12%), renal failure (8%), coronary artery vasculopathy (6%) and re-transplantation (5%). Among 64 survivors, 84% were free of complications affecting prognosis. High waiting-list mortality and post-transplant attrition precluded 60% of this pioneer population from reaching adulthood. Functional status in survivors is generally good. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

[Hypertension and pregnancy: Post-partum period].

PubMed

Hugon-Rodin, Justine; Plu-Bureau, Geneviève

2016-01-01

Post-partum period is associated with specific characteristics in women with gestational disorders or preeclampsia. For breastfeeding women, the choice of antihypertensive treatment should take into account the impact on child health. The impact of breastfeeding on health mother must be also discussed. Moreover, for lactation inhibition, bromocriptine should not be used, especially in the context of gestational disorders. In post-partum period, the best contraceptive strategy is only-progestin contraception or non-hormonal contraceptives use. However, this choice will depend on the stabilization or normalization of blood pressure in early post-partum period. Finally, several consultations should be suggested: an information and announcement to explain the consequences of these gestational disorders and organize their multidisciplinary management and follow-up. A preconceptional consultation takes its place to anticipate potential recurrent preeclampsia or gestational hypertension and to schedule a future pregnancy in optimal conditions. Copyright © 2016. Published by Elsevier Masson SAS.

Modeling the effects of functional performance and post-transplant comorbidities on health-related quality of life after heart transplantation.

PubMed

Butler, Javed; McCoin, Nicole S; Feurer, Irene D; Speroff, Theodore; Davis, Stacy F; Chomsky, Don B; Wilson, John R; Merrill, Walter H; Drinkwater, Davis C; Pierson, Richard N; Pinson, C Wright

2003-10-01

Health-related quality of life and functional performance are important outcome measures following heart transplantation. This study investigates the impact of pre-transplant functional performance and post-transplant rejection episodes, obesity and osteopenia on post-transplant health-related quality of life and functional performance. Functional performance and health-related quality of life were measured in 70 adult heart transplant recipients. A composite health-related quality of life outcome measure was computed via principal component analysis. Iterative, multiple regression-based path analysis was used to develop an integrated model of variables that affect post-transplant functional performance and health-related quality of life. Functional performance, as measured by the Karnofsky scale, improved markedly during the first 6 months post-transplant and was then sustained for up to 3 years. Rejection Grade > or =2 was negatively associated with health-related quality of life, measured by Short Form-36 and reversed Psychosocial Adjustment to Illness Scale scores. Patients with osteopenia had lower Short Form-36 physical scores and obese patients had lower functional performance. Path analysis demonstrated a negative direct effect of obesity (beta = - 0.28, p < 0.05) on post-transplant functional performance. Post-transplant functional performance had a positive direct effect on the health-related quality of life composite score (beta = 0.48, p < 0.001), and prior rejection episodes grade > or =2 had a negative direct effect on this measure (beta = -0.29, p < 0.05). Either directly or through effects mediated by functional performance, moderate-to-severe rejection, obesity and osteopenia negatively impact health-related quality of life. These findings indicate that efforts should be made to devise immunosuppressive regimens that reduce the incidence of acute rejection, weight gain and osteopenia after heart transplantation.

Tuberculosis post-liver transplantation: a rare but complicated disease.

PubMed

Lu, W; Wai, C T; Da Costa, M; Tambyah, P A; Prabhakaran, K; Lee, K H

2005-03-01

Tuberculosis is a rare but serious complication after transplantation. We report a case and discuss its presentation and management. A 60-year-old Indonesian male presented initially with fever, acute confusion and rapidly progressive right upper lobe pneumonia 3.5 months post-liver transplant, and was diagnosed with pulmonary tuberculosis by positive sputum smear for acid-fast bacilli and tuberculosis culture. Standard anti-tuberculosis therapy was administered but was complicated by interaction with cyclosporine and drug-induced cholestasis. A high level of suspicion, prompt antituberculosis treatment and close follow-up are essential in management of post-transplant tuberculosis.

[Affective syndromes in liver transplant recipients: ¿mediated neurotoxicity immunosuppressive?].

PubMed

Restrepo, Diana Patricia; Tamayo, Alejandra

2015-01-01

The onset of affective and psychotic in liver transplant patients symptoms, raises the need to explore the possible etiologies of mental symptoms. Case report and literature review. Four clinical cases of patients undergoing orthotopic liver transplantation, who in the early post transplant showed affective symptoms, delusions and psychomotor agitation for which they needed psychiatric hospitalization and treatment with psychotropic drugs are presented. Three of the patients had clinical improvement and one patient died by suicide. The development of mental symptoms in the post-transplant period opens the possibility of considering the secondary organic mental disorder a basic condition. The adverse drug reaction may explain affective mental disorders in these four cases were reported. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients - BCSH and BTS Guidelines.

PubMed

Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

2010-06-01

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder (PTLD) in adult recipients of solid organ transplants. This review details the risk factors predisposing to development, initial features and diagnosis. It is important that the risk of developing PTLD is considered when using post transplant immunosuppression and that the appropriate investigations are carried out when there are suspicions of the diagnosis. These must include tissue for histology and computed tomography scan to assess the extent of disease. These recommendations have been made primarily for adult patients, there have been some comments made with regard to paediatric practice.

Early onset primary pulmonary cryptococcosis in a renal transplant patient.

PubMed

Tarai, B; Kher, V; Kotru, P; Sabhikhi, A; Barman, P; Rattan, A

2010-01-01

We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB). Broncho-alveolar fluid (BAL) shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold) in serum and was negative in cerebrospinal fluid (CSF). The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.

Predictors of post-traumatic psychological growth in the late years after lung transplantation.

PubMed

Fox, Kristen R; Posluszny, Donna M; DiMartini, Andrea F; DeVito Dabbs, Annette J; Rosenberger, Emily M; Zomak, Rachelle A; Bermudez, Christian; Dew, Mary Amanda

2014-04-01

Although lung transplantation improves quality of life, most psychosocial research focuses on adverse psychological and social functioning outcomes. Positive effects, particularly in the late-term years as physical morbidities increase, have received little attention. We provide the first data on a psychological benefit - post-traumatic growth (PTG) - and we focused on long-term (>5 yr) survivors. Among 178 patients from a prospective study of mental health during the first two yr post-transplant, we recontacted survivors 6-11 yr post-transplant. We assessed PTG (i.e., positive psychological change resulting from the transplant) and examined its relationship to other patient characteristics with multivariable regression analyses. Sixty-four patients (86% of survivors) were assessed (M = 8.1 yr post-transplant, SD = 1.2). Mean PTG exceeded the scale's midpoint (M = 38.6, SD = 10.0; scale midpoint = 25). Recipients experiencing greater PTG were female (p = 0.022), less educated (p = 0.014), and had a history of post-transplant panic disorder (p = 0.005), greater friend support (p = 0.048), and better perceived health (p = 0.032). Neither other pre- or post-transplant mood and anxiety disorders nor transplant-related morbidities (acute rejection, bronchiolitis obliterans syndrome) predicted PTG. PTG exceeded levels observed in other chronic disease populations, suggesting that lung transplantation may uniquely foster positive psychological change in long-term survivors. PTG occurs despite physical and psychiatric morbidities. Whether PTG promotes other positive post-transplant psychosocial outcomes deserves attention. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pre- and post- transplantation lung cancer in heart transplant recipients.

PubMed

Pricopi, Ciprian; Rivera, Caroline; Varnous, Shaida; Arame, Alex; Le Pimpec Barthes, Françoise; Riquet, Marc

2015-05-01

Heart transplantation after lung cancer surgery can be questionable because of the high risk of cancer recurrence. We report the results of two patients. The first underwent right lobectomy in 2008 for pT1N0 adenocarcinoma, heart-transplantation in 2010, and surgery for synchronous adenocarcinoma and squamous-cell carcinoma in 2012. The second underwent left segmentectomy for pT1aN0 adenosquamous carcinoma and transplantation in 1995 and then surgery for pT1aN1 adenocarcinoma in 2013. Posttransplantation lung cancer histologic analysis results were different in both cases, demonstrating the absence of metastatic recurrence. Thus, early stage lung cancer might not be a contraindication to heart transplantation, nor are long delays be necessary before registering on a waiting list. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

T-cell acute lymphoblastic leukaemia after liver transplantation: post-transplant lymphoproliferative disorder or coincidental de novo leukaemia?

PubMed

Fang, Yanan; Pinkney, Kerice A; Lee, John C; Gindin, Tatyana; Weiner, Michael A; Alobeid, Bachir; Bhagat, Govind

2013-03-01

Post-transplant lymphoproliferative disorders of T-cell origin are quite uncommon, and the vast majority represent neoplasms of mature, post-thymic T- or natural killer cells. Here, we report a rare case of T-cell acute lymphoblastic leukaemia (T-ALL), which occurred in an 18-year-old man who had undergone three liver transplants, initially for biliary atresia and subsequently for graft failure due to chronic rejection. He had received immunosuppression with cyclosporine and tacrolimus, as well as short-term treatment with OKT3. The T-ALL occurred 16 years after the first liver transplant. This case highlights the challenge for classifying rare neoplasms occurring in recipients of solid organ transplants that are currently not recognized to lie within the spectrum of post-transplant lymphoproliferative disorders. Given the long interval between the liver transplants and the development of T-ALL, a coincidental occurrence of the leukaemia cannot be ruled out. However, the potential roles of immunosuppressive therapy and other co-morbid conditions of the individual as possible risk factors for the pathogenesis of T-ALL are discussed. Copyright © 2012 John Wiley & Sons, Ltd.

Management of Non-Diffuse Large B Cell Lymphoma Post-Transplant Lymphoproliferative Disorder.

PubMed

Major, Ajay; Kamdar, Manali

2018-05-24

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common neoplasms seen after solid organ and hematopoietic stem cell transplantation, and is associated with significant morbidity and mortality. The pathogenesis is related to post-transplant immunosuppression and EBV infection. Prevention of PTLD depends upon judicious use of immunosuppression and serial EBV monitoring. Preemptive therapy consists of reduction of immunosuppression, antiviral medications, and single-agent rituximab. There are no randomized phase III trials on PTLD treatment, so current management guidelines are largely based on recent phase II trials, single-institution retrospective studies, and expert opinion. Management of PTLD is dependent upon its subtypes. Early-type and polymorphic PTLD generally respond to reduction of immunosuppression and rituximab monotherapy, whereas monomorphic PTLD often requires additional concurrent or sequential use of chemotherapy. For rare subtypes of PTLD, standard-of-care guidelines for de novo lymphomas are recommended. Surgical resection or radiotherapy may be used as adjunctive therapy depending on the extent of disease. Non-chemotherapy options such as adoptive T cell therapy have shown promising efficacy and must be explored further. Despite progress in the last decade, overall survival rates continue to be low in published series. This review highlights the need for prospective randomized trials incorporating novel agents to improve outcomes in PTLD.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury

PubMed Central

Lo, Wai-Kit; Burakoff, Robert; Goldberg, Hilary J; Feldman, Natan; Chan, Walter W

2015-01-01

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux

Using OCT to predict post-transplant renal function

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Chen, Yu; Wierwille, Jeremiah; Joh, Daniel; Alexandrov, Peter; Rogalsky, Derek; Moody, Patrick; Chen, Allen; Cooper, Matthew; Verbesey, Jennifer E.; Gong, Wei; Wang, Hsing-Wen

2013-03-01

The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of "optical biopsy", providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

Early pneumopericardium after heart transplantation.

PubMed

Duero Posada, Juan G; Moayedi, Yasbanoo; Alhussein, Mosaad; Bunce, Paul E; Yau, Terrence M; Ross, Heather J

2018-02-01

A 60-year-old woman with a history of dilated cardiomyopathy underwent heart transplantation. One month post discharge, she presented to clinic with low-grade fever and productive cough. Her chest radiograph showed air-fluid levels in the pericardial silhouette. Transthoracic echocardiogram showed a large complex pericardial collection with no evidence of cardiac tamponade. The patient was urgently taken to the operating room for exploration. A large "egg-shaped" mass in the pericardium measuring 10 × 12 cm with gaseous material was aspirated. As the posterior wall of the mass was firmly adhered to the right atrium, the capsule was incompletely excised. We present the case of a potentially life-threatening complication post transplantation that required surgical debridement and life-long antibiotic suppressive therapy. To our knowledge, this is the first report of purulent pericardial collection caused by Enterobacter cancerogenous. Further research is required to better understand the biology of this microorganism and the role it may play as a pathogen in immunocompromised patients following solid organ transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Post-transplantation Infections in Bolivia.

PubMed

Arze, S; Arze, L; Abecia, C

2016-03-01

Over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. Fifteen were urinary tract infections, recurrent in 4 patients. There were 8 cytomegalovirus infections, three of them fatal when intravenous (IV) ganciclovir was not available. Seven patients had a reactivation of tuberculosis (TB) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-TB therapy. Three patients transplanted before routine prophylaxis with the use of acyclovir developed an extensive herpes zoster infection in the 1st 6 months after transplantation, which was resolved with the use of oral acyclovir, and 1 had a disseminated herpes simplex infection resolved with the use of IV acyclovir. Three patients transplanted before routine prophylaxis with trimethoprim sulfa developed Pneumocystis carinii pneumonia in the 1st 6 months after transplantation, which was fatal in one of them. In 2 patients, we found a Nocardia infection, confined to the lung, which was cured in one of the cases and systemic and fatal in the other. Two patients transplanted before routine prophylaxis with the use of nystatin developed esophageal candidiasis in the 1st 6 months after transplantation. One patient developed infective endocarditis in a stenotic bicuspid aortic valve and died 10 years later after another incident of infective endocarditis at the prosthetic aortic valve. Two patients developed an extensive condyloma at the penis, perianal region, and perineum owing to human papillomavirus, requiring extensive surgical resection and podophyllin applications. Another patient developed fatal post-transplantation lymphoproliferative disease due to Epstein-Barr virus infection 15 years after transplantation. One patient developed a severe and fatal mucocutaneous leishmaniasis with no response to conventional antimonial therapy. It is interesting to note that despite Chagas disease being endemic

Maintenance steroid use at 30 days post-transplant and outcomes of pediatric heart transplantation: A propensity matched analysis of the Pediatric Heart Transplant Study database.

PubMed

Auerbach, Scott R; Kukreja, Manisha; Gilbert, Deborah; Bastardi, Heather; Feingold, Brian; Knecht, Kenneth; Kaufman, Beth D; Brown, Robert N; Miyamoto, Shelley D

2015-08-01

Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes. All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups. Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively). MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

One-Year Review of the SCREEN (Skin Cancer Post-Transplant) Clinic.

PubMed

Baldwin, Sarah; Au, Sheila

The Skin Cancer Post-Transplant (SCREEN) Clinic is a skin-cancer screening clinic that is fully integrated into the renal transplantation clinic at St Paul's Hospital in Vancouver, British Columbia. The purpose of this review was to determine characteristics of patients most at risk for skin cancer, to specify types and locations of skin cancers diagnosed, and to identify areas for patient and physician education. Transplant patients (91% renal; 5% heart) screened by a dermatologist during a 12-month period were stratified into low-, medium-, and high-risk groups based on detailed history and skin examination. In total, 118 skin cancers were diagnosed. White males were found to be most at risk. Squamous cell carcinoma accounted for the majority of tumours, over 25% of which demonstrated invasion. Forty-two percent of patients used only 1 to 2 bottles of sunscreen per year, and sun-protective practices were limited. With this information, we have identified potential target areas for patient and physician education.

An evaluation of the impact of donor BMI on survival and post-transplant obesity in pediatric liver transplant recipients

PubMed Central

Perito, Emily Rothbaum; Rhee, Sue; Glidden, Dave; Roberts, John Paul; Rosenthal, Philip

2012-01-01

Introduction In adult liver transplant recipients, donor BMI is associated with post-transplant obesity but not graft or patient survival. Given the U.S. obesity epidemic and already-limited supply of liver donors, clarifying whether donor BMI affects pediatric outcomes is important. Methods UNOS data on pediatric U.S. liver transplants 1990-2010 was evaluated. Data on transplants 2004-2010 (n=3788) was used for survival analysis with Kaplan-Meier and Cox proportional hazards models and for post-transplant obesity analysis with generalized estimating equations. Results For children receiving adult donor livers, donor BMI 25-35 kg/m2 was not associated with graft or patient survival in univariate or multivariate analyses. Donor BMI>35 kg/m2 increased the risk of graft loss (HR 2.54, 95%CI 1.29-5.01, p=0.007) and death (HR 3.56, 95%CI 1.64-7.72, p=0.001). For pediatric donors, donor BMI was not associated with graft loss or mortality in univariate or multivariate analysis. Donor overweight/obesity was not a risk factor for post-transplant obesity. Conclusions Overweight/obesity is common among liver transplant donors. This analysis suggests that for adult donors, BMI 25-35 should not by itself be a contraindication to liver donation. Severe obesity (BMI>35) in adult donors increased the risk of graft loss and mortality, even after adjustment for recipient, donor, and transplant risk factors. Post-transplant obesity was not associated with donor BMI in this analysis. Further research is needed to clarify the impact of donor obesity on pediatric liver transplant recipients. PMID:22467594

Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia.

PubMed

Lovisa, Federica; Zecca, Marco; Rossi, Bartolomeo; Campeggio, Mimma; Magrin, Elisa; Giarin, Emanuela; Buldini, Barbara; Songia, Simona; Cazzaniga, Giovanni; Mina, Tommaso; Acquafredda, Gloria; Quarello, Paola; Locatelli, Franco; Fagioli, Franca; Basso, Giuseppe

2018-03-01

Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%. The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10 -3 and ≥1 × 10 -3 , respectively, versus 73% in MRD-negative patients (P < 0·001). This effect was maintained in different disease remissions, but low-level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post-HSCT1 and post-HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre-emptive immuno-therapy. © 2018 John Wiley & Sons Ltd.

Post-transplant lymphoproliferative disorder and management of residual mass post chemotherapy: Case report.

PubMed

Schultz, Troy D; Zepeda, Nubia; Moore, Ronald B

2017-01-01

Post-transplant lymphoproliferative disorder (PTLD) is a rare complication. It represents a spectrum of lymphoid proliferations which occur in the setting of immunosuppression and organ transplantation. There are no reported cases or recommendations for the treatment of residual masses post rituximab of PTLD. A patient with a long standing history of immunosuppression due to multiple kidney transplants starting in 1979, presented with a very large palpable hard abdominal mass (2004) after a fourth renal transplant. There was a past history of heavy immune suppression. CT scans revealed a conglomerate mass involving the right native kidney and two prior right sided renal allografts that crossed the midline. Biopsy of the large right retroperitoneal mass revealed large B cell lymphoma (CD 20 positive); consistent with post-transplant lymphoproliferative disorder (PTLD). Management of bulky PTLD, in a highly sensitized, heavily immune suppressed patient is not well described in the literature. The mainstay of therapy is IR and Ritixumab (R) monotherapy and combination R-CHOP. CHOP chemotherapy has an associated mortality rate of up to 38%. Radiotherapy is often considered over surgery and surgery has been most frequently used when associated with bowel complications. In this case report we describe upfront Ritiximab followed by consolidation resection and cytotoxic chemotherapy as a management strategy to reduce toxicity. The approach taken by our surgical team illustrates the benefits of disease debulking in certain cases of PTLD, by guiding further therapy and spacing and reducing chemotherapy in immune suppressed patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Overview of adult congenital heart transplants

PubMed Central

Morales, David

2018-01-01

Transplantation for adult patients with congenital heart disease (ACHD) is a growing clinical endeavor in the transplant community. Understanding the results and defining potential high-risk patient subsets will allow optimization of patient outcomes. This review summarizes the scope of ACHD transplantation, the mechanisms of late ventricular dysfunction, the ACHD population at risk of developing heart failure, the indications and potential contraindications for transplant, surgical considerations, and post-transplant outcomes. The findings reveal that 3.3% of adult heart transplants occur in ACHD patients. The potential mechanisms for the development of late ventricular dysfunction include a morphologic systemic right ventricle, altered coronary perfusion, and ventricular noncompaction. The indications for transplant in ACHD patients include systemic ventricular failure refractory medical therapy, Fontan patients failing from chronic passive pulmonary circulation, and progressive cyanosis leading to functional decline. Transplantation in ACHD patients can be quite complex and may require extensive reconstruction of the branch pulmonary arteries, systemic veins, or the aorta. Vasoplegia, bleeding, and graft right ventricular dysfunction can complicate the immediate post-transplant period. The post-transplant operative mortality ranges between 14% and 39%. The majority of early mortality occurs in ACHD patients with univentricular congenital heart disease. However, there has been improvement in operative survival in more contemporary studies. In conclusion, the experience with cardiac transplantation for ACHD patients with end-stage heart failure is growing, and high-risk patient subsets have been defined. Significant strides have been made in developing evidence-based guidelines of indications for transplant, and the intraoperative management of complex reconstruction has evolved. With proper patient selection, more aggressive use of mechanical circulatory support

Benefit of early inflow exclusion during living donor liver transplantation for unresectable hepatoblastoma.

PubMed

Uchida, Hajime; Fukuda, Akinari; Sasaki, Kengo; Hirata, Yoshihiro; Shigeta, Takanobu; Kanazawa, Hiroyuki; Nakazawa, Atsuko; Miyazaki, Osamu; Nosaka, Shunsuke; Mali, Vidyadhar Padmakar; Sakamoto, Seisuke; Kasahara, Mureo

2016-11-01

Hepatoblastoma (HB) is a highly malignant primary liver tumor in children. Although liver transplantation (LT) is an effective treatment for unresectable HB with good long-term outcomes, post-transplant survival is mainly affected by recurrence, despite adjuvant chemotherapy. Novel strategies are needed to improve the outcomes in patients undergoing LT for unresectable HB. Twelve children received LT for unresectable HB. In 9 patients, we applied early exclusion of hepatic inflow (hepatic artery and portal vein) and creation of a temporary portocaval shunt during LT. There were differences in the duration of and the blood loss during operation as compared with previously reports. The estimated glomerular filtration rate was well preserved at 3, 6, and 12months and the latest follow-up after LT, and the recurrence-free survival was 88.9%. Early inflow control during LT for unresectable HB may benefit recurrence-free survival by minimizing blood loss and tumor dissemination, preserving renal function and allowing early adjuvant chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Laparoscopic Repair of Incisional Hernia Following Liver Transplantation-Early Experience of a Single Institution in Taiwan.

PubMed

Kuo, S-C; Lin, C-C; Elsarawy, A; Lin, Y-H; Wang, S-H; Wu, Y-J; Chen, C-L

2017-10-01

Ventral incisional hernia (VIH) is not uncommon following liver transplantation. Open repair was traditionally adopted for its management. Laparoscopic repair of VIH has been performed successfully in nontransplant patients with evidence of reduced recurrence rates and hospital stay. However, the application of VIH in post-transplantation patients has not been well established. Herein, we provide our initial experience with laparoscopic repair of post-transplantation VIH. From March 2015 to March 2016, 18 cases of post-transplantation VIH were subjected to laparoscopic repair (laparoscopy group). A historical control group of 17 patients who underwent conventional open repair (open group) from January 2013 to January 2015 were identified for comparison. The demographics and clinical outcomes were retrospectively compared. There were no significant differences among basic demographics between the 2 groups. No conversion was recorded in the laparoscopy group. Recurrence of VIH up to the end of the study period was not noted. In the laparoscopy group, the minor complications were lower (16.7% vs 52.9%; P = .035), the length of hospital stay was shorter (3 d vs 7 d, P = .007), but the median operative time was longer (137.5 min vs 106 min; P = .003). Laparoscopic repair of post-transplantation VIH is a safe and feasible procedure with shorter length of hospital stay. Copyright © 2017 Elsevier Inc. All rights reserved.

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor.

PubMed

Bashey, A; Solomon, S R

2014-08-01

Availability of an HLA-identical sibling (MRD) or suitably matched unrelated donor (MUD) has historically been a limiting factor in the application of allogeneic hematopoietic transplantation. Although almost all patients have an HLA-haploidentical family donor, prior attempts at transplantation from such donors using T-cell replete grafts and conventional immunosuppression were associated with unacceptable rates of GVHD, and when stringent ex vivo T-cell depletion was used to control GVHD, rates of graft rejection and post-transplant infections were prohibitive. The recent approach to HLA-haploidentical donor transplantation developed in Baltimore that uses T-cell replete grafts and post-transplant CY (Haplo-post-HCT-CY) to control post-transplant allo-reactivity appears to have overcome many of the obstacles historically associated with haploidentical donor transplantation. In particular, TRM rates of <10% are usual and rapid reconstitution of immunity leads to a low rate of post-transplant infections and no post-tranplant lymphoproliferative disorders (PTLD), consistent with the hypothesis that post-transplant CY selectively depletes proliferating alloreactive T cells responsible for GVHD and graft rejection while preserving resting memory T cells essential for post-transplant immunologic recovery. In parallel trials using similar non-myeloablative conditioning regimens, Haplo-post-HCT-CY produced similar overall survival to double umbilical cord blood transplantation(DUCBT) in adult patients (62% vs 54%), with low rates of TRM (7% vs 24%), severe acute GVHD (0% vs 21%) and chronic GVHD (13% vs 25%). Furthermore, recent non-randomized comparisons adjusted for risk factors show that Haplo-post-HCT-CY achieve at least equivalent outcomes to conventional MRD and MUD transplants. Although most experience has been obtained using BM, emerging data suggest that a G-CSF mobilized PBSC graft can also safely be used for Haplo-post-HCT-CY. Haplo-post-HCT-CY also avoids the

Post-Transplantation Natural Killer Cell Count: A Predictor of Acute Graft-Versus-Host Disease and Survival Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Kim, Seo Yeon; Lee, Hyewon; Han, Mi-Soon; Shim, Hyoeun; Eom, Hyeon-Seok; Park, Boram; Kong, Sun-Young

2016-09-01

Reconstitution of the immune system after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in post-transplant outcomes. However, the clinical relevance of the lymphocyte subset (LST) counts to transplant-related complications and survival outcomes after allo-HSCT has not been fully elucidated. A total of 70 patients who had undergone allo-HSCT from 2007 to 2013, with LST results both 7 days before conditioning and 30 or 90 days after allo-HSCT were included. The LST counts in the peripheral blood were determined using 6-color flow cytometry. Clinical information, including transplant-related events during the first 100 days after allo-HSCT, was reviewed, and any association between these events and LST was analyzed. At 30 days after allo-HSCT, the CD4 + T-cell (P = .009) and B-cell (P = .035) counts were lower and the natural killer (NK) cell count was greater (P < .001) than before conditioning. The CD8 + T-cell (P = .001) and NK cell (P < .001) counts were high 90 days after transplantation. The hazard ratios for a low NK cell count on days 30 and 90 for acute graft-versus-host disease were 6.22 and 14.67, respectively. Patients with low NK cell counts at 30 and 90 days after allo-HSCT had poorer overall survival (P = .043 and P = .028, respectively) and greater nonrelapse mortality (P = .036 and P = .033, respectively). A low NK cell count on day 30 was still prognostic for overall survival (P = .039) on multivariable analysis. NK cell counts after allo-HSCT, especially on day 30, were predictive of acute graft-versus-host disease, nonrelapse mortality, and survival. Serial lymphocyte subset analysis can be used to identify and treat patients at risk during the early period after allo-HSCT. Copyright © 2016 Elsevier Inc. All rights reserved.

Alcohol abuse in deceased liver donors: impact on post-transplant outcomes.

PubMed

Mangus, Richard S; Kubal, Chandrashekhar A; Fridell, Jonathan A; Pena, Jose M; Frost, Evan M; Joseph Tector, A

2015-01-01

Many deceased liver donors with a history of alcohol abuse are excluded based upon medical history alone. This paper summarizes the transplant outcomes for a large number of deceased liver donors with a documented history of alcohol abuse. The records for 1478 consecutive deceased liver donors were reviewed (2001-2012). As per the United Network for Organ Sharing criteria, heavy alcohol use by an organ donor is defined as chronic intake of two or more drinks per day. Donors with a documented history of alcohol abuse were divided into three groups according to duration of abuse (<10 years, 10-24 years and 25 + years). Reperfusion biopsies are reported. Outcomes include biopsy appearance, early graft function and early and late graft survival. There were 161 donors with alcohol abuse: <10 years (29%); 10-24 years (42%); and ≥25 years (29%). Risk of 90-day graft loss for these three groups was: 0%, 3% and 2%, compared to 3% for all other donors (P = 0.62). Graft survival at 1 year for donor grafts with and without alcohol abuse was 89% and 87% (P = 0.52). There was no difference in early graft function. Cox proportional hazards modelling for graft survival demonstrates no statistically significant difference in survival up to 10 years post-transplant. This study demonstrates successful transplantation of a large number of deceased donor liver grafts from donors with a documented history of alcohol abuse (n = 161; 11% of all grafts). These extended criteria donor allografts may, therefore, be utilized successfully with similar outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A new data-driven model for post-transplant antibody dynamics in high risk kidney transplantation.

PubMed

Zhang, Yan; Briggs, David; Lowe, David; Mitchell, Daniel; Daga, Sunil; Krishnan, Nithya; Higgins, Robert; Khovanova, Natasha

2017-02-01

The dynamics of donor specific human leukocyte antigen antibodies during early stage after kidney transplantation are of great clinical interest as these antibodies are considered to be associated with short and long term clinical outcomes. The limited number of antibody time series and their diverse patterns have made the task of modelling difficult. Focusing on one typical post-transplant dynamic pattern with rapid falls and stable settling levels, a novel data-driven model has been developed for the first time. A variational Bayesian inference method has been applied to select the best model and learn its parameters for 39 time series from two groups of graft recipients, i.e. patients with and without acute antibody-mediated rejection (AMR) episodes. Linear and nonlinear dynamic models of different order were attempted to fit the time series, and the third order linear model provided the best description of the common features in both groups. Both deterministic and stochastic parameters are found to be significantly different in the AMR and no-AMR groups showing that the time series in the AMR group have significantly higher frequency of oscillations and faster dissipation rates. This research may potentially lead to better understanding of the immunological mechanisms involved in kidney transplantation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Temporal trends in early clinical outcomes and health care resource utilization for liver transplantation in the United States.

PubMed

Scarborough, John E; Pietrobon, Ricardo; Marroquin, Carlos E; Tuttle-Newhall, Janet E; Kuo, Paul C; Collins, Bradley H; Desai, Dev M; Pappas, Theodore N

2007-01-01

Procedures such as liver transplantation, which entail large costs while benefiting only a small percentage of the population, are being increasingly scrutinized by third-party payors. The purpose of our study was to conduct a longitudinal analysis of the early clinical outcomes and health care resource utilization for liver transplantation in the United States. The Nationwide Inpatient Sample database was used to conduct a longitudinal analysis of the clinical outcome and resource utilization data for liver transplantation procedures in adult recipients performed in the United States over three time periods (Period I: 1988-1993; Period II: 1994-1998: Period III: 1999-2003). Compared to Period I, adult liver transplant recipients were more likely to be male, older, and non-White in Period III. Recipients were more likely to have at least one major comorbidity preoperatively than in Period I. The in-hospital mortality rate after liver transplantation decreased significantly from Period I to Period III, but the major intraoperative and postoperative complication rates increased over the same time period. Mean length of hospital stay decreased over the 15-year period, but the percentage of patients with a non-routine discharge status increased. Our findings indicate that the rate of postoperative complications and non-routine discharges after liver transplantation is increasing. However, these negative changes in the cost-outcomes relationship for liver transplantation are balanced by improving postoperative survival rates and reductions in the length of hospital stay.

Existence of circulating anti-endothelial cell antibodies after heart transplantation is associated with post-transplant acute allograft rejection.

PubMed

Lehle, Karla; Kroher, Johannes; Kolat, Philipp; von Süßkind-Schwendi, Marietta; Schmid, Christof; Haneya, Assad; Rupprecht, Leopold; Hirt, Stephan

2016-05-01

Anti-endothelial cell antibodies (AECA) may be involved in the development of heart allograft rejection. Its detection might be a cheap and noninvasive method to identify high-risk patients. An indirect immunofluorescence method on human umbilical vein endothelial cells was used to investigate the presence of AECAs in 260 pre- and post-transplant serum samples sequentially collected from 34 patients within the first year after heart transplantation (HTX). The presence of AECAs before (23.5 %) and early after HTX (14.7 %) was associated with a significantly increased risk of early acute rejection (75 and 60 %, respectively) compared to 33 % in AECA-negative patients (p = 0.049). Moreover, rejections from AECA-positive patients were more severe (p = 0.057) with a significantly increased incidence of multiple (p = 0.025). The mean number of the sum of rejection episodes was significantly higher in AECA-positive patients (p ≤ 0.05). Patients free of AECAs mainly received mycophenolate mofetil as primary immunosuppression (p = 0.067). Nevertheless, the presence of AECAs did not affect long-term outcome and mortality of HTX patients. Despite a low number of patient samples, the detection of AECAs before and early after HTX could be used as a biomarker for an increased risk of early acute rejection in high-risk patients. This easy method might be a valuable tool to support screening procedures to improve individualized immunosuppressive therapy.

Unperturbed vs. post-transplantation hematopoiesis: both in vivo but different

PubMed Central

Busch, Katrin; Rodewald, Hans-Reimer

2016-01-01

Purpose of review Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking techniques now shed light on hematopoiesis under physiological conditions. Recent findings Transposon-based genetic marks were introduced across the entire hematopoietic system to follow the clonal dynamics of these tags over time. A polyclonal source downstream from stem cells was found responsible for the production of at least granulocytes. In independent experiments, HSCs were genetically marked in adult mice, and the kinetics of label emergence throughout the system was followed over time. These experiments uncovered that during physiological steady-state hematopoiesis large numbers of HSCs yield differentiated progeny. Individual HSCs were active only rarely, indicating their very slow periodicity of differentiation rather than quiescence. Summary Noninvasive genetic experiments in mice have identified a major role of stem and progenitor cells downstream from HSCs as drivers of adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs quantitatively from normal steady-state hematopoiesis. PMID:27213498

Unperturbed vs. post-transplantation hematopoiesis: both in vivo but different.

PubMed

Busch, Katrin; Rodewald, Hans-Reimer

2016-07-01

Hematopoietic stem cell (HSC) transplantation has yielded tremendous information on experimental properties of HSCs. Yet, it remains unclear whether transplantation reflects the physiology of hematopoiesis. A limitation is the difficulty in accessing HSC functions without isolation, in-vitro manipulation and readout for potential. New genetic fate mapping and clonal marking techniques now shed light on hematopoiesis under physiological conditions. Transposon-based genetic marks were introduced across the entire hematopoietic system to follow the clonal dynamics of these tags over time. A polyclonal source downstream from stem cells was found responsible for the production of at least granulocytes. In independent experiments, HSCs were genetically marked in adult mice, and the kinetics of label emergence throughout the system was followed over time. These experiments uncovered that during physiological steady-state hematopoiesis large numbers of HSCs yield differentiated progeny. Individual HSCs were active only rarely, indicating their very slow periodicity of differentiation rather than quiescence. Noninvasive genetic experiments in mice have identified a major role of stem and progenitor cells downstream from HSCs as drivers of adult hematopoiesis, and revealed that post-transplantation hematopoiesis differs quantitatively from normal steady-state hematopoiesis.

Liver alone or simultaneous liver-kidney transplant? Pretransplant chronic kidney disease and post-transplant outcome - a retrospective study.

PubMed

Nagai, Shunji; Safwan, Mohamed; Collins, Kelly; Schilke, Randolph E; Rizzari, Michael; Moonka, Dilip; Brown, Kimberly; Patel, Anita; Yoshida, Atsushi; Abouljoud, Marwan

2018-05-02

The new Organ Procurement and Transplant Network/United Organ Sharing Network (OPTN/UNOS) simultaneous liver-kidney transplant (SLK) policy has been implemented. The aim of this study was to review liver transplant outcomes utilizing the new SLK policy. Liver transplant alone (LTA) and SLK patients between 2009 and 2015 were reviewed. Graft survival and post-transplant kidney function were investigated among LTA patients meeting the chronic kidney disease (CKD) criteria of the new policy (LTA-CKD group). To validate our findings, we reviewed and applied our analysis to the OPTN/UNOS registry. A total of 535 patients were eligible from our series. The LTA-CKD group (n = 27) showed worse 1-year graft survival, compared with the SLK group (n = 44), but not significant (81% vs. 93%, P = 0.15). The LTA-CKD group significantly increased a risk of post-transplant dialysis (odds ratio = 5.59 [95% CI = 1.27-24.7], P = 0.02 [Ref. normal kidney function]). Post-transplant dialysis was an independent risk factor for graft loss (hazard ratio = 7.25, 95% CI = 3.3-15.91, P < 0.001 [Ref. SLK]). In the validation analysis based on the OPTN/UNOS registry, the hazard of 1-year-graft loss in the LTA-CKD group (n = 751) was 34.8% higher than the SLK group (n = 2856) (hazard ratio = 1.348, 95% CI = 1.157-1.572, P < 0.001). Indicating SLK for patients who meet the CKD criteria may significantly improve transplant outcomes. © 2018 Steunstichting ESOT.

Severe right ventricular dysfunction is an independent predictor of pre- and post-transplant mortality among candidates for heart transplantation.

PubMed

Ravis, Eleonore; Theron, Alexis; Mancini, Julien; Jaussaud, Nicolas; Morera, Pierre; Chalvignac, Virginie; Guidon, Catherine; Grisoli, Dominique; Gariboldi, Vlad; Riberi, Alberto; Habib, Gilbert; Mouly-Bandini, Annick; Collart, Frederic

2017-03-01

Heart transplantation is the gold-standard treatment for end-stage heart failure. However, the shortage of grafts has led to longer waiting times and increased mortality for candidates without priority. To study waiting-list and post-transplant mortality, and their risk factors among patients registered for heart transplantation without initial high emergency procedure. All patients registered on the heart transplantation waiting list (2004-2015) without initial high emergency procedure were included. Clinical, biological, echocardiographic and haemodynamic data were collected. Waiting list and 1-year post-transplant survival were analysed with a Kaplan-Meier model. Of 221 patients enrolled, 168 (76.0%) were men. Mean age was 50.0±12.0 years. Forty-seven patients died on the waiting list, resulting in mortality rates of 11.2±2.7% at 1 year, 31.9±5.4% at 2 years and 49.4±7.1% at 3 years. Median survival was 36.0±4.6 months. In the multivariable analysis, left ventricular ejection fraction<30% (hazard ratio [HR]: 3.76, 95% confidence interval [CI]: 1.38-10.24; P=0.010) and severe right ventricular systolic dysfunction (HR: 2.89, 95% CI: 1.41-5.92; P=0.004) were associated with increased waiting-list mortality. The post-transplant survival rate was 73.1±4.4% at 1 year. Pretransplant severe right ventricular dysfunction and age>50 years were strong predictors of death after transplantation (HR: 5.38, 95% CI: 1.38-10.24 [P=0.020] and HR: 6.16, 95% CI: 1.62-9.32 [P=0.0130], respectively). Mortality among candidates for heart transplantation remains high. Patients at highest risk of waiting-list mortality have to be promoted, but without compromising post-transplant outcomes. For this reason, candidates with severe right ventricular dysfunction are of concern, because, for them, transplantation is hazardous. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation.

PubMed

Hong, Gina; White, Marissa; Lechtzin, Noah; West, Natalie E; Avery, Robin; Miller, Heather; Lee, Richard; Lovari, Robert J; Massire, Christian; Blyn, Lawrence B; Liang, Xinglun; Sutton, Deanna A; Fu, Jianmin; Wickes, Brian L; Wiederhold, Nathan P; Zhang, Sean X

2017-03-01

Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies. We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation. We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host. Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines.

PubMed

Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

2010-06-01

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi-organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

Survival of Mexican children with acute myeloid leukaemia who received early intensification chemotherapy and an autologous transplant.

PubMed

Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Villegas, Octavio Martínez; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

2015-01-01

In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005-2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999-2004, was treated as Group A, but without the early intensified chemotherapy. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

Nutrition in liver transplantation: too little or too much?

PubMed

Plank, Lindsay D; Russell, Kylie

2015-09-01

The purpose of this study was to review the most recent findings on approaches to managing the obesity and muscle wasting that are found in patients before and after liver transplantation. A number of articles have contributed to the accumulating evidence that morbid obesity is not an absolute contraindication to liver transplantation with survival outcomes similar across BMI groups. Obesity is, however, a risk factor for early post-transplant complications and obesity-related comorbidities markedly increase this risk. Very limited data are as yet available, dietary, or otherwise, related to amelioration of these comorbidities and evidence that weight loss leads to improved outcomes in obese patients is lacking. Abdominal computed tomography imaging is increasingly being used to identify muscle wasting, and poorer post-transplant survival is seen in patients with significant muscle wasting. This modality has confirmed the persistence of depleted muscle stores after transplant extending well beyond 1 year. Coupled with this is a high incidence of weight gain and metabolic syndrome and the associated risks. Although dietary intervention and exercise are considered possible approaches to address these issues, work in these areas so far is sparse. An urgent need exists for interventional studies on the basis of nutrition and/or exercise to address the challenges presented by both obesity and muscle wasting, which likely coexist in many patients in both the pretransplant and the post-transplant periods.

Early polymerase chain reaction detection of Chagas disease reactivation in heart transplant patients.

PubMed

da Costa, Priscilla Almeida; Segatto, Marcela; Durso, Danielle Fernandes; de Carvalho Moreira, Wagson José; Junqueira, Lucas Lodi; de Castilho, Fábio Morato; de Andrade, Silvio Amadeu; Gelape, Cláudio Léo; Chiari, Egler; Teixeira-Carvalho, Andréa; Junho Pena, Sergio Danilo; Machado, Carlos Renato; Franco, Gloria Regina; Filho, Geraldo Brasileiro; Vieira Moreira, Maria da Consolação; Mara Macedo, Andréa

2017-07-01

Heart transplantation is a valuable therapeutic option for Chagas disease patients with severe cardiomyopathy. During patient follow-up, the differential diagnosis between cardiac transplant rejection and Chagas disease infection reactivation remains a challenging task, which hinders rapid implementation of the appropriate treatment. Herein we investigate whether polymerase chain reaction (PCR) strategies could facilitate early detection of Trypanosoma cruzi (T cruzi) in transplanted endomyocardial biopsies (EMBs). In this study we analyzed 500 EMB specimens obtained from 58 chagasic cardiac transplant patients, using PCR approaches targeted to nuclear (rDNA 24Sα) and kinetoplastid (kDNA) markers, and compared the efficiency of these approaches with that of other tests routinely used. T cruzi DNA was detected in 112 EMB specimens derived from 39 patients (67.2%). The first positive result occurred at a median 1.0 month post-transplant. Conventional histopathologic, blood smear and hemoculture analyses showed lower sensitivity and higher median time to the first positive result. Patient follow-up revealed that 31 of 39 PCR-positive cases presented clinical reactivation of Chagas disease at different time-points after transplantation. PCR techniques showed considerable sensitivity (0.82) and specificity (0.60), with area under the receiver operating characteristic (ROC) curves of 0.708 (p = 0.001). Moreover, PCR techniques anticipated the clinical signs of Chagas disease reactivation by up to 36 months, with a median time of 6 months and an average of 9.1 months. We found a good association between the PCR diagnosis and the clinical signs of the disease, indicating that the PCR approaches used herein are suitable for early diagnosis of Chagas disease reactivation, with high potential to assist physicians in treatment decisions. For this purpose, an algorithm is proposed for surveillance based on the molecular tests. Copyright © 2017 International Society for the

Early viral-specific T-cell testing predicts late Cytomegalovirus reactivation following Liver Transplantation.

PubMed

Sood, S; Haifer, C; Yu, L; Pavlovic, J; Gow, P J; Jones, R M; Visvanathan, K; Angus, P W; Testro, A G

2018-05-29

Although antiviral prophylaxis is effective in preventing early cytomegalovirus (CMV) reactivation following liver transplantation (OLT), it predisposes patients to late CMV after prophylaxis has ceased. QuantiFERON-CMV (QFN-CMV, Qiagen, The Netherlands) measures an individual's viral-specific immune response. Fifty-nine OLT recipients were prospectively monitored post-OLT in an observational cohort study. QFN-CMV was performed at regular time-points. An absolute QFN-CMV <0.1IU/mL was considered non-reactive. 50/59 (84.7%) had a reactive QFN-CMV by M6. 38/59 (64.4%) had antiviral prophylaxis or treatment before M6, with 31/38 (81.6%) developing a reactive QFN-CMV by 6 months. Over 90% already had a reactive result as early as 3 months post-transplant. 3 patients (5.08%) developed late CMV between 6-12 months (median 251 days) - all had a non-reactive M6 QFN-CMV. 2/3 experienced CMV disease. Non-reactive M6 QFN-CMV was significantly associated with late CMV (OR=54.4, PPV=0.33, NPV=1.00, p=0.003). Although only 5% of recipients developed late CMV, 2/3 suffered CMV disease. M6 QFN-CMV has an excellent NPV for late CMV, suggesting patients who exhibit a robust ex-vivo immune response at M6 can safely cease CMV monitoring. Furthermore, >90% already express viral-specific immunity as early as 3 months. Conceivably, antiviral prophylaxis could be discontinued early in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Initial Steroid Sensitivity in Children with Steroid-Resistant Nephrotic Syndrome Predicts Post-Transplant Recurrence

PubMed Central

Ding, Wen Y.; Koziell, Ania; McCarthy, Hugh J.; Bierzynska, Agnieszka; Bhagavatula, Murali K.; Dudley, Jan A.; Inward, Carol D.; Coward, Richard J.; Tizard, Jane; Reid, Christopher; Antignac, Corinne; Boyer, Olivia

2014-01-01

Of children with idiopathic nephrotic syndrome, 10%–20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%–50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P<0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence. PMID:24511128

Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation.

PubMed

Ma, Y-R; Xu, L-P; Zhang, X-H; Yan, C-H; Wang, Y; Wang, F-R; Wang, J-Z; Chen, Y; Han, W; Chen, Y-H; Chen, H; Liu, K-Y; Huang, X-J

2017-03-01

We investigated the impact of donor type on post-relapse survival (PRS) in 85 patients with hematological relapse after their first allogeneic hematological stem cell transplantation (allo-HSCT) for hematological malignancy. The median follow-up was 64 months among survivors. Both 3-year overall survival and 3-year PRS were similar in haploidentical donor (HID) and matched sibling donor (MRD) transplantation (13.0%±4.7% vs 19.4%±7.1%, P=0.913 and 7.7±3.9% vs 9.7±5.3%, P= 0.667). Higher rates of post-relapse grade II-IV and III-IV acute GvHD (aGvHD) were observed in HID transplantation patients. A higher cumulative incidence of post-relapse extensive chronic GvHD was also observed for HID transplantation patients. Multivariate analyses confirmed that treatment including donor lymphocyte infusion (DLI), late relapse >1 year, and in first CR at transplantation were associated with superior PRS (P=0.012, hazard ratio (HR)=0.527 (0.320-0.866)); P=0.033, HR=0.534 (0.300-0.952) and P=0.046, HR=0.630 (0.400-0.992). The data suggest that post-relapse outcomes are comparable in HID and MRD transplantation, and that DLI is safe for relapsed patients after haploidentical transplantation.

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes.

PubMed

Shivaswamy, Vijay; Boerner, Brian; Larsen, Jennifer

2016-02-01

Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

PubMed Central

Shivaswamy, Vijay; Boerner, Brian

2016-01-01

Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM. PMID:26650437

Post-transplant survival in idiopathic pulmonary fibrosis patients concurrently listed for single and double lung transplantation.

PubMed

Chauhan, Dhaval; Karanam, Ashwin B; Merlo, Aurelie; Tom Bozzay, P A; Zucker, Mark J; Seethamraju, Harish; Shariati, Nazly; Russo, Mark J

2016-05-01

Lung transplantation is a widely accepted treatment for patients with end-stage lung disease related to idiopathic pulmonary fibrosis (IPF). However, there are conflicting data on whether double lung transplant (DLT) or single lung transplant (SLT) is the superior therapy in these patients. The purpose of this study was to determine whether actuarial post-transplant graft survival among IPF patients concurrently listed for DLT and SLT is greater for recipients undergoing the former or the latter. The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant candidates with IPF listed between January 1, 2001 and December 31, 2009 (n = 3,411). The study population included 1,001 (29.3%) lung transplant recipients concurrently listed for DLT and SLT, all ≥18 years of age. The primary outcome measure was actuarial post-transplant graft survival, expressed in years. Among the study population, 433 (43.26%) recipients underwent SLT and 568 (56.74%) recipients underwent DLT. The analysis included 2,722.5 years at risk, with median graft survival of 5.31 years. On univariate (p = 0.317) and multivariate (p = 0.415) regression analyses, there was no difference in graft survival between DLT and SLT. Among IPF recipients concurrently listed for DLT and SLT, there is no statistical difference in actuarial graft survival between recipients undergoing DLT vs SLT. This analysis suggests that increased use of SLT for IPF patients may increase the availability of organs to other candidates, and thus increase the net benefit of these organs, without measurably compromising outcomes. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The evolving role of alemtuzumab (Campath-1H) in renal transplantation

PubMed Central

Pham, Phuong-Thu T; Lipshutz, Gerald S; Pham, Phuong-Truc T; Kawahji, Joseph; Singer, Jennifer S; Pham, Phuong-Chi T

2009-01-01

The introduction of new immunosuppressive agents into clinical transplantation in the 1990s has resulted in excellent short-term graft survival. Nonetheless, extended long-term graft outcomes have not been achieved due in part to the nephrotoxic effects of calcineurin inhibitors (CNIs) and the adverse effects of steroid on cardiovascular disease risk factors. Induction therapy with lymphocyte depleting antibodies has originally been introduced into renal transplantation to provide intense immunosuppression in the early post-transplant period to prevent allograft rejection. Over the past half decade, induction therapy with both non-lymphocyte depleting (basiliximab and daclizumab) and lymphocyte-depleting antibodies (antithymocyte antibodies, OKT3, alemtuzumab) has increasingly been utilized in steroid or CNI sparing protocols in the early postoperative period. Alemtuzumab is a humanized monoclonal antibody targeted against CD52 on the surface of circulatory mononuclear cells. The ability of alemtuzumab (Campath-1H) to provide rapid and profound depletion of lymphocytes from the peripheral blood has sparked interest in the use of this agent as induction therapy in steroid and/or CNI minimization or avoidance protocols. This article provides an overview of the literarure on the evolving role of alemtuzumab in renal transplantation. PMID:19920920

Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival in Acute Lymphoblastic Leukemia: A CIBMTR Analysis.

PubMed

Wood, William A; Brazauskas, Ruta; Hu, Zhen-Huan; Abdel-Azim, Hisham; Ahmed, Ibrahim A; Aljurf, Mahmoud; Badawy, Sherif; Beitinjaneh, Amer; George, Biju; Buchbinder, David; Cerny, Jan; Dedeken, Laurence; Diaz, Miguel Angel; Freytes, Cesar O; Ganguly, Siddhartha; Gergis, Usama; Almaguer, David Gomez; Gupta, Ashish; Hale, Gregory; Hashmi, Shahrukh K; Inamoto, Yoshihiro; Kamble, Rammurti T; Adekola, Kehinde; Kindwall-Keller, Tamila; Knight, Jennifer; Kumar, Lalit; Kuwatsuka, Yachiyo; Law, Jason; Lazarus, Hillard M; LeMaistre, Charles; Olsson, Richard F; Pulsipher, Michael A; Savani, Bipin N; Schultz, Kirk R; Saad, Ayman A; Seftel, Matthew; Seo, Sachiko; Shea, Thomas C; Steinberg, Amir; Sullivan, Keith; Szwajcer, David; Wirk, Baldeep; Yared, Jean; Yong, Agnes; Dalal, Jignesh; Hahn, Theresa; Khera, Nandita; Bonfim, Carmem; Atsuta, Yoshiko; Saber, Wael

2018-03-19

For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed using the following macroeconomic indicators as main effects: Gross national income per capita, health expenditure per capita, and Human Development Index (HDI). The outcome was overall survival at 100 days following transplantation. In each model, transplants performed within lower resourced environments were associated with inferior overall survival. In the model with the HDI as the main effect, transplants performed in the lowest HDI quartile (n = 697) were associated with increased hazard for mortality (hazard ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with transplants performed in the countries with the highest HDI quartile. This translated into an 11% survival difference at 100 days (77% for lowest HDI quartile versus 88% for all other quartiles). Country-level macroeconomic indices were associated with lower survival at 100 days after alloHCT for ALL. The reasons for this disparity require further investigation. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prophylactic eculizumab for kidney transplantation in a child with atypical hemolytic uremic syndrome due to complement factor H mutation.

PubMed

Ranch, Daniel; Crowther, Barrett; Arar, Mazen; Assanasen, Chatchawin

2014-09-01

We present a case of successful deceased-donor kidney transplantation in a three-yr-old child with aHUS due to complement factor H mutation, using only prophylactic eculizumab treatment prior to transplant. She developed disease exacerbation in the immediate post-operative period despite having therapeutic eculizumab concentrations and evidence for complete complement pathway blockade. The patient responded well to additional doses of eculizumab and has maintained excellent graft function and disease control in the first year post-transplantation. The optimal dosing scheme for eculizumab in the perioperative period remains to be determined. More sensitive biomarkers of early disease activity are needed to improve disease monitoring. Finally, the duration of eculizumab therapy in patients with aHUS remains to be determined. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

PubMed Central

Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

2015-01-01

Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Safe and effective treatment of early suprahepatic inferior vena caval outflow compromise following orthotopic liver transplantation using percutaneous transluminal angioplasty and stent placement.

PubMed

Tasse, Jordan; Borge, Marc; Pierce, Kenneth; Brems, John

2011-01-01

To describe the safety and efficacy of percutaneous transluminal angioplasty and stent placement in patients presenting with suprahepatic inferior vena cava (IVC) outflow compromise in the early postoperative period following orthotopic liver transplantation. Between October 2002 and April 2009, 3 patients presented with IVC outflow compromise in the first 2 months following orthotopic liver transplantation. All 3 underwent percutaneous transluminal angioplasty and stent placement without complication and showed significant clinical improvement at short and intermediate term follow-up. Percutaneous transluminal angioplasty and Gianturco stent placement is a safe and effective treatment for IVC outflow compromise in the early postoperative period following orthotopic liver transplantation.

The incidence of non-melanoma skin cancer and post-transplant lympho-proliferative disorders in the Scottish cardiac transplant population and the provision of specialist dermatological follow-up.

PubMed

McPherson, Iain; Kirk, Alan

2017-01-01

Background Immunosuppression helps prevent acute rejection post-cardiac transplant but has been linked to malignancy development. This may be due to a reduction in T-lymphocyte function, a direct oncogenic effect or the increased impact of environmental carcinogens. There has been shown to be significant increases in non-melanoma skin cancers and post-transplant lympho-proliferative disorders, particularly in those treated with OKT3. Aim To investigate the survival and incidence of malignancy in the Scottish cardiac transplant population and whether rates of non-melanoma skin cancers justify the provision of specialist dermatological follow-up. Methods and results Retrospective case note analysis of patients transplanted (363) or followed up (2) in Scotland from 1992 to 2016. Kaplan-Meier survival analysis generated a survival curve. Patients had a 1-year survival of 82% and a median survival of 10.9 years. There were 60 (95% CI 47.5, 75.2) NMSCs and 8 (3.7, 12.4) post-transplant lympho-proliferative disorders diagnosed in the cohort (3110 person years follow-up). Fisher's exact test was employed to analyse the association between induction therapy (via OKT3 or rabbit antithymocyte globulin) and post-transplant lympho-proliferative disorder development. Patients treated with OKT3 had a 6.7 times greater risk ( P = 0.014) and a shorter experience of patients treated with rabbit antithymocyte globulin has so far shown no significantly altered risk ( P = 1.00) of developing a post-transplant lympho-proliferative disorder. Conclusion Incidences of non-melanoma skin cancers and post-transplant lympho-proliferative disorders were increased in the Scottish cardiac transplant population and there was a significant association between post-transplant lympho-proliferative disorder development and OKT3 therapy but not rabbit antithymocyte globulin therapy. These findings in Scottish patients reflect what is published in wider literature and support the provision of a

Is early removal of prophylactic ureteric stents beneficial in live donor renal transplantation?

PubMed Central

Indu, K. N.; Lakshminarayana, G.; Anil, M.; Rajesh, R.; George, K.; Ginil, K.; Georgy, M.; Nair, B.; Sudhindran, S.; Appu, T.; Unni, V. N.; Sanjeevan, K. V.

2012-01-01

Prophylactic ureteric stenting has been shown to reduce ureteric leaks and collecting system obstruction following renal transplantation and is in widespread use. However, the optimal time for removal of ureteric stents after renal transplantation remains unclear. Aim of this study was to compare the result of early versus late removal of ureteric stents after kidney transplantation of the laparoscopically retrieved live related donor grafts. Eligible patients were live donor kidney transplant recipients with normal urinary tracts. All recipients underwent extravesical Lich–Gregoire ureteroneocystostomy over 4F/160 cm polyurethane double J stents by a uniform technique. They were randomized on seventh postoperative day for early removal of stents on postoperative day 7 (Group I), or for late removal on postoperative day 28 (Group II). The incidence of urinary tract infections, asymptomatic bacteriuria, and urological complications were compared. Between 2007 and 2009, 130 kidney transplants were performed at one centre of which 100 were enrolled for the study, and 50 each were randomized into the two groups. Donor and recipient age, sex, native renal disease, immunosupression, number of rejection episodes, and antirejection therapy were similar in the two groups. The occurrence of symptomatic urinary tract infection during the follow-up period of 6 months was significantly less in the early stent removal group [5 out of 50 (10%) in Group I, vs 50 out of 15 (30%) in Group II, P=0.02]. Asymptomatic bacteriuria was documented in 2 out of 50 (4%) in Group I and 4 out of 50 (8%) in Group II (P=0.3). There was no statistically significant difference in the rate of ureteric leak, ureteric obstruction, or hematuria in the two groups (P=1.0). We conclude that, in kidney transplant recipients of laparoscopically retrieved live donor grafts, early stent removal at the end of first week reduces the incidence of urinary tract infection without increasing the rate of urine

Dry period management and optimization of post-partum reproductive management in dairy cattle.

PubMed

Gumen, A; Keskin, A; Yilmazbas-Mecitoglu, G; Karakaya, E; Wiltbank, Mc

2011-09-01

Dry period and early post-partum management are decisive factors for fertility in lactating dairy cows. Previous studies have shown that decreased dry matter intake (DMI) and increased non-esterified fatty acids (NEFA) negatively affect fertility and subsequent milk production. The traditional dry period decreases DMI prior to parturition, resulting in a decrease in energy intake. A negative energy balance increases NEFA concentration, and increased NEFA may impair the immune system, especially by decreasing neutrophil function prior to parturition. Earlier studies have shown that post-partum health disorders, including retained placenta and metritis, were correlated with periparturient neutrophil function. In addition, decreased DMI is also linked to a reduced body condition score (BCS) in dairy cows. These events in the periparturient period negatively affect fertility. Some manipulation, such as shortening the dry period, may be a solution to increased DMI in the periparturient period, preventing post-partum disorders and subsequent fertility issues. This article aims to explain the effects of shortening the dry period on reproduction and early post-partum treatments to improve fertility. In addition, timed artificial insemination protocols will be discussed for use during the post-partum period to improve fertility in dairy cows. © 2011 Blackwell Verlag GmbH.

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

PubMed

Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

2018-02-01

Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

Central nervous system complications after liver transplantation.

PubMed

Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

2015-08-01

We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Amiodarone use in patients listed for heart transplant is associated with increased 1-year post-transplant mortality.

PubMed

Cooper, Lauren B; Mentz, Robert J; Edwards, Leah B; Wilk, Amber R; Rogers, Joseph G; Patel, Chetan B; Milano, Carmelo A; Hernandez, Adrian F; Stehlik, Josef; Lund, Lars H

2017-02-01

Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes. We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score. Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups. Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Validation of a Pediatric Early Warning Score in Hospitalized Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients.

PubMed

Agulnik, Asya; Forbes, Peter W; Stenquist, Nicole; Rodriguez-Galindo, Carlos; Kleinman, Monica

2016-04-01

To evaluate the correlation of a Pediatric Early Warning Score with unplanned transfer to the PICU in hospitalized oncology and hematopoietic stem cell transplant patients. We performed a retrospective matched case-control study, comparing the highest documented Pediatric Early Warning Score within 24 hours prior to unplanned PICU transfers in hospitalized pediatric oncology and hematopoietic stem cell transplant patients between September 2011 and December 2013. Controls were patients who remained on the inpatient unit and were matched 2:1 using age, condition (oncology vs hematopoietic stem cell transplant), and length of hospital stay. Pediatric Early Warning Scores were documented by nursing staff at least every 4 hours as part of routine care. Need for transfer was determined by a PICU physician called to evaluate the patient. A large tertiary/quaternary free-standing academic children's hospital. One hundred ten hospitalized pediatric oncology patients (42 oncology, 68 hematopoietic stem cell transplant) requiring unplanned PICU transfer and 220 matched controls. None. Using the highest score in the 24 hours prior to transfer for cases and a matched time period for controls, the Pediatric Early Warning Score was highly correlated with the need for PICU transfer overall (area under the receiver operating characteristic = 0.96), and in the oncology and hematopoietic stem cell transplant groups individually (area under the receiver operating characteristic = 0.95 and 0.96, respectively). The difference in Pediatric Early Warning Score results between the cases and controls was noted as early as 24 hours prior to PICU admission. Seventeen patients died (15.4%). Patients with higher Pediatric Early Warning Scores prior to transfer had increased PICU mortality (p = 0.028) and length of stay (p = 0.004). We demonstrate that our institution's Pediatric Early Warning Score is highly correlated with the need for unplanned PICU transfer in hospitalized oncology and

Risk for Clostridium difficile Infection After Allogeneic Hematopoietic Cell Transplant Remains Elevated in the Postengraftment Period.

PubMed

Dubberke, Erik R; Reske, Kimberly A; Olsen, Margaret A; Bommarito, Kerry M; Seiler, Sondra; Silveira, Fernanda P; Chiller, Tom M; DiPersio, John; Fraser, Victoria J

2017-04-01

Clostridium difficile infection (CDI) is a frequent cause of diarrhea among allogeneic hematopoietic cell transplant (HCT) recipients. It is unknown whether risk factors for CDI vary by time posttransplant. We performed a 3-year prospective cohort study of CDI in allogeneic HCT recipients. Participants were enrolled during their transplant hospitalizations. Clinical assessments were performed weekly during hospitalizations and for 12 weeks posttransplant, and monthly for 30 months thereafter. Data were collected through patient interviews and chart review, and included CDI diagnosis, demographics, transplant characteristics, medications, infections, and outcomes. CDI cases were included if they occurred within 1 year of HCT and were stratified by time from transplant. Multivariable logistic regression was used to determine risk factors for CDI. One hundred eighty-seven allogeneic HCT recipients were enrolled, including 63 (34%) patients who developed CDI. 38 (60%) CDI cases occurred during the preengraftment period (days 0-30 post-HCT) and 25 (40%) postengraftment (day >30). Lack of any preexisting comorbid disease was significantly associated with lower risk of CDI preengraftment (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.9). Relapsed underlying disease (OR, 6.7; 95% CI, 1.3-33.1), receipt of any high-risk antimicrobials (OR, 11.8; 95% CI, 2.9-47.8), and graft-versus-host disease (OR, 7.8; 95% CI, 2.0-30.2) were significant independent risk factors for CDI postengraftment. A large portion of CDI cases occurred during the postengraftment period in allogeneic HCT recipients, suggesting that surveillance for CDI should continue beyond the transplant hospitalization and preengraftment period. Patients with continued high underlying severity of illness were at increased risk of CDI postengraftment.

Early postoperative pulmonary complications after heart transplantation.

PubMed

Camkiran Firat, A; Komurcu, O; Zeyneloglu, P; Turker, M; Sezgin, A; Pirat, A

2015-05-01

The aim of this study was to determine the types, incidence, and risk factors for early postoperative pulmonary complications in heart transplant recipients. We retrospectively collected data from the records of consecutive heart transplantations from January 2003 to December 2013. A total of 83 patients underwent heart transplantation. The data collected for each case were demographic features, duration of mechanical ventilation, respiratory problems that developed during the intensive care unit (ICU) stay, and early postoperative mortality (<30 d). Of the 72 patients considered, 52 (72.2%) were male. The overall mean age at the time of transplantation was 32.1 ± 16.6 years. Twenty-five patients (34.7%) developed early postoperative respiratory complications. The most frequent problem was pleural effusion (n = 19; 26.4%), followed by atelectasis (n = 6; 8.3%), acute respiratory distress syndrome (n = 5; 6.9%), pulmonary edema (n = 4; 5.6%), and pneumonia (n = 3; 4.2%). Postoperative duration of mechanical ventilation (44.2 ± 59.2 h vs 123.8 ± 190.8 h; P = .005) and the length of postoperative ICU stay (10.1 ± 5.8 h vs 19.8 ± 28.9 h; P = .03) were longer among patients who had respiratory problems. Postoperative length of stay in the hospital (22.3 ± 12.5 d vs 30.3 ± 38.3 d; P = .75) was similar in the 2 groups. The overall mortality rate was 12.5% (n = 9). The patients who had respiratory problems did not show higher mortality than those who did not have respiratory problems (16.0% vs 10.6%; P = .71). Respiratory complications were relatively common in our cohort of heart transplant recipients. However, these complications were mostly self-limiting and did not result in worse mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Immunosuppressive Agents on Hepatocyte Apoptosis Post-Liver Transplantation

PubMed Central

Lim, Eu Jin; Chin, Ruth; Nachbur, Ueli; Silke, John; Jia, Zhiyuan; Angus, Peter W.; Torresi, Joseph

2015-01-01

Introduction Immunosuppressants are used ubiquitously post-liver transplantation to prevent allograft rejection. However their effects on hepatocytes are unknown. Experimental data from non-liver cells indicate that immunosuppressants may promote cell death thereby driving an inflammatory response that promotes fibrosis and raises concerns that a similar effect may occur within the liver. We evaluated apoptosis within the liver tissue of post-liver transplant patients and correlated these findings with in vitro experiments investigating the effects of immunosuppressants on apoptosis in primary hepatocytes. Methods Hepatocyte apoptosis was assessed using immunohistochemistry for M30 CytoDEATH and cleaved PARP in human liver tissue. Primary mouse hepatocytes were treated with various combinations of cyclosporine, tacrolimus, sirolimus, or MMF. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved PARP and cleaved caspase 3. Results Post-liver transplant patients had a 4.9-fold and 1.7-fold increase in M30 CytoDEATH and cleaved PARP compared to normal subjects. Cyclosporine and tacrolimus at therapeutic concentrations did not affect hepatocyte apoptosis, however when they were combined with MMF, cell death was significantly enhanced. Cell viability was reduced by 46% and 41%, cleaved PARP was increased 2.6-fold and 2.2-fold, and cleaved caspase 3 increased 2.2-fold and 1.8-fold following treatment with Cyclosporine/MMF and Tacrolimus/MMF respectively. By contrast, the sirolimus/MMF combination did not significantly reduce hepatocyte viability or promote apoptosis. Conclusion Commonly used immunosuppressive drug regimens employed after liver transplantation enhance hepatocyte cell death and may thus contribute to the increased liver fibrosis that occurs in a proportion of liver transplant recipients. PMID:26390404

The Affordable Care Act Medicaid Expansion Correlated With Increased Heart Transplant Listings In African-Americans But Not Hispanics Or Caucasians

PubMed Central

Breathett, Khadijah; Allen, Larry A.; Helmkamp, Laura; Colborn, Kathryn; Daugherty, Stacie L.; Khazanie, Prateeti; Lindrooth, Richard; Peterson, Pamela

2016-01-01

Objectives The aim of this study was to determine if the Affordable Care Act (ACA) Medicaid Expansion was associated with increased census-adjusted heart transplant listing rates for racial/ethnic minorities. Background Underinsurance limits access to transplants, especially among racial/ethnic minorities. Changes in racial/ethnic listing rates post the ACA Medicaid Expansion are unknown. Methods Using the Scientific Registry of Transplant Recipients, we analyzed 5,651 patients from early adopter states (implemented ACA Medicaid Expansion by 1/2014) and 4,769 patients from non-adopter states (no implementation during study period) from 2012–2015. Piecewise linear models, stratified by race/ethnicity, were fit to monthly census-adjusted rates of heart transplant listings before and after 1/2014. Results A significant 30% increase in the rate of heart transplant listings for African-Americans in early adopter states occurred immediately following the ACA Medicaid Expansion on 1/1/2014 [pre 0.15 to post 0.20/100,000, increase 0.05/100,000 (95%Confidence Interval (CI): 0.01,0.08)]; in contrast, the rates for African-Americans in non-adopter states remained constant [pre and post 0.15/100,000, increase 0.006/100,000 (95%CI: −0.03,0.04)]. Hispanics experienced an opposite trend, with no significant change in early adopter states [pre 0.03 to post 0.04/100,000, increase 0.01/100,000 (95%CI: −0.004,0.02)] and a significant increase in non-adopter states [pre 0.03 to post 0.05/100,000, increase 0.02/100,000 (95%CI: 0.002,0.03)]. There were no significant changes in listing rates among Caucasians in either early adopter or non-adopter states. Conclusions Implementation of the ACA Medicaid Expansion was associated with increased heart transplant listings in African-Americans but not Hispanics or Caucasians. Broadening of the ACA in states with large African-American populations may reduce disparities in heart transplant listings. PMID:28109783

Recent advances in the risk factors, diagnosis and management of Epstein-Barr virus post-transplant lymphoproliferative disease.

PubMed

Aguayo-Hiraldo, Paibel; Arasaratnam, Reuben; Rouce, Rayne H

Fifty years after the first reports of Epstein-Barr virus (EBV)-associated endemic Burkitt's lymphoma, EBV has emerged as the third most prevalent oncogenic virus worldwide. EBV infection is associated with various malignancies including Hodgkin and non-Hodgkin lymphoma, NK/T-cell lymphoma and nasopharyngeal carcinoma. Despite the highly specific immunologic control in the immunocompetent host, EBV can cause severe complications in the immunocompromised host (namely, post-transplant lymphoproliferative disease). This is particularly a problem in patients with delayed immune reconstitution post-hematopoietic stem cell transplant or solid organ transplant. Despite advances in diagnostic techniques and treatment algorithms allowing earlier identification and treatment of patients at highest risk, mortality rates remain as high as 90% if not treated early. The cornerstones of treatment include reduction in immunosuppression and in vivo B cell depletion with an anti-CD20 monoclonal antibody. However, these treatment modalities are not always feasible due to graft rejection, emergence of graft vs. host disease, and toxicity. Newer treatment modalities include the use of adoptive T cell therapy, which has shown promising results in various EBV-related malignancies. In this article we will review recent advances in risk factors, diagnosis and management of EBV-associated malignancies, particularly post-transplant lymphoproliferative disease. We will also discuss new and innovative treatment options including adoptive T cell therapy as well as management of special situations such as chronic active EBV and EBV-associated hemophagocytic lymphohistiocytosis. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Disseminated Aspergillus fumigatus infection with consecutive mitral valve endocarditis in a lung transplant recipient.

PubMed

Scherer, Mirela; Fieguth, Hans-Gerd; Aybek, Tayfun; Ujvari, Zsolt; Moritz, Anton; Wimmer-Greinecker, Gerhard

2005-12-01

Aspergillus infection is a known complication of lung transplantation and remains associated with high mortality rates. The manifestation of the infection varies from simple colonization of the lung to disseminated complicated infections. Early Aspergillus infection has been rarely observed in a small number of lung transplant recipients; most cases occur during the late post-operative period. The pulmonary involvement has often been described as the first clinical localization of the disease. Although other various forms of Aspergillus infection are not uncommonly encountered after lung transplantation, Aspergillus mitral valve endocarditis is rare. We present a case of disseminated Aspergillus fumigatus infection with consecutive mitral valve endocarditis having developed 78 days after double-lung transplantation for cystic fibrosis.

Cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in seropositive kidney transplant recipients

PubMed Central

Ryu, Ji Hyeong; Choi, Ae-Ran; Yu, Ji Hyun; Lim, Jihyang; Han, Kyungja; Kim, Sang Il; Yang, Chul Woo; Chung, Byung Ha

2017-01-01

Although cytomegalovirus (CMV) specific cell-mediated immunity (CMI) has been suggested as a predictive marker for CMV infection, proper CMI monitoring strategy in CMV-seropositive recipients and optimal method are not defined. The aim of this study was to evaluate two interferon gamma release assays during early post-transplant period as a predictor of the development of CMV infection in CMV-seropositive patients. A total of 124 CMV-seropositive recipients who received kidney transplantation from CMV-seropositive donor were prospectively examined. At pre-transplant and post-transplant 1 and 3 months, CMV-CMIs were tested using QuantiFERON-CMV assay (QF-CMV) and CMV specific T cell ELISPOT against CMV pp65 and IE-1 antigens (pp65-ELISPOT, IE-1-ELISPOT). CMV DNAemia occurred in 16 (12.9%) patients within 3 months after transplant. Post-transplant pp65 or IE-1 ELISPOT response, but not QF-CMV, was significantly associated with CMV DNAemia. The pp65 ELISPOT (cut-off; 30 spots/200,000 cells) and IE-1 ELISPOT (10 spots/200,000 cells) at post-transplant 1 month predicted the risk of post-transplant CMV DNAemia (P = 0.019). Negative predictive values (NPV) for protection from CMV DNAemia in case of positive ELISPOT results were 94.5% (95% CI: 86.9–97.8%) and 97.6% (95% CI: 86.3–99.6%) in pp65-ELISPOT and IE-1-ELISPOT assays, respectively. These results suggest that the variability may exist between CMV ELISPOT assays and QF-CMV, and CMV ELISPOT at post-transplant 1 month can identify the risk of CMV DNAemia in seropositive kidney transplant recipients. PMID:29232714

Cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in seropositive kidney transplant recipients.

PubMed

Lee, Hyeyoung; Park, Ki Hyun; Ryu, Ji Hyeong; Choi, Ae-Ran; Yu, Ji Hyun; Lim, Jihyang; Han, Kyungja; Kim, Sang Il; Yang, Chul Woo; Chung, Byung Ha; Oh, Eun-Jee

2017-01-01

Although cytomegalovirus (CMV) specific cell-mediated immunity (CMI) has been suggested as a predictive marker for CMV infection, proper CMI monitoring strategy in CMV-seropositive recipients and optimal method are not defined. The aim of this study was to evaluate two interferon gamma release assays during early post-transplant period as a predictor of the development of CMV infection in CMV-seropositive patients. A total of 124 CMV-seropositive recipients who received kidney transplantation from CMV-seropositive donor were prospectively examined. At pre-transplant and post-transplant 1 and 3 months, CMV-CMIs were tested using QuantiFERON-CMV assay (QF-CMV) and CMV specific T cell ELISPOT against CMV pp65 and IE-1 antigens (pp65-ELISPOT, IE-1-ELISPOT). CMV DNAemia occurred in 16 (12.9%) patients within 3 months after transplant. Post-transplant pp65 or IE-1 ELISPOT response, but not QF-CMV, was significantly associated with CMV DNAemia. The pp65 ELISPOT (cut-off; 30 spots/200,000 cells) and IE-1 ELISPOT (10 spots/200,000 cells) at post-transplant 1 month predicted the risk of post-transplant CMV DNAemia (P = 0.019). Negative predictive values (NPV) for protection from CMV DNAemia in case of positive ELISPOT results were 94.5% (95% CI: 86.9-97.8%) and 97.6% (95% CI: 86.3-99.6%) in pp65-ELISPOT and IE-1-ELISPOT assays, respectively. These results suggest that the variability may exist between CMV ELISPOT assays and QF-CMV, and CMV ELISPOT at post-transplant 1 month can identify the risk of CMV DNAemia in seropositive kidney transplant recipients.

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial.

PubMed

Nashan, Bjorn; Schemmer, Peter; Braun, Felix; Dworak, Markus; Wimmer, Peter; Schlitt, Hans

2015-03-26

Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy. The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients. Hephaistos is an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll 330 de novo liver transplant recipients from 15 centers across Germany. Patients are randomized in a 1:1 ratio (7-21 days post-transplantation) to receive everolimus (trough levels 3-8 ng/mL) with reduced tacrolimus (trough levels <5 ng/mL), or standard tacrolimus (trough levels 6-10 ng/mL) after entering a run-in period (3-5 days post-transplantation). In the run-in period, patients are treated with induction therapy, mycophenolate mofetil, tacrolimus, and corticosteroids according to local practice. Randomization is stratified by HCV status and model of end-stage liver disease scores at transplantation. The primary objective of the study is to exhibit superior renal function (estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard tacrolimus at Month 12. Other objectives are: to assess the incidence of treated biopsy-proven acute rejection, graft loss, or death; the incidences of components of the composite efficacy endpoint; renal function via estimated glomerular filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft

Re-Transplantation, Higher Creatinine Levels in Hepatitis C Virus Patients, and Donor Age Are Predictors of Mortality in Long-Term Analysis of Late Acute Rejection in Liver Transplantation.

PubMed

Nacif, Lucas Souto; Pinheiro, Rafael Soares; de Arruda Pécora, Rafael Antônio; Tanigawa, Ryan Yukimatsu; Rocha-Santos, Vinicius; Andraus, Wellington; Alves, Venancio Avancini Ferreira; D'Albuquerque, Luiz Carneiro

2017-01-10

BACKGROUND Late acute rejection (LAR) differs in its clinical and histological presentation and management from early acute rejection. This clinical entity is not completely understood; thus, we aimed to identify significant prognostic factors that can influence post-transplant survival in LAR patients. The purpose of this study was to evaluate the incidence and post-transplant survival of patients from a single center with a focus on late acute rejection. MATERIAL AND METHODS From January 2002 to June 2013, all liver biopsies from patients with rejection were scored using the Banff criteria. The groups were compared, and simple and multiple logistic regression and survival curves were created. RESULTS A total of 779 liver transplants were performed; 585 patients with no rejections and 194 patients with rejections were analyzed. The overall incidence of LAR was 6.7%, and there was a higher prevalence of early acute cellular rejection than LAR. The mean time to LAR was 564 days (median 214 days, range 91-2642). LAR had a more severe grade (35.3%) than early acute rejection (23.5%). The survival rates were similar between both modalities for the long-term period. Worse mortality rates were observed in liver re-transplantation (HR 4.77; p<0.0001); in hepatitis C virus patients with increased creatinine levels (HR 22.48; p=0.016); and in donors >41 years of age (OR 2.1; p=0.047) in a long-term analysis of LAR. CONCLUSIONS Liver re-transplantation, higher creatinine levels in hepatitis C virus patients, and donor age were predictors of mortality in this long-term analysis of late acute rejection in liver transplantation.

Variables associated with the risk of early death after liver transplantation at a liver transplant unit in a university hospital.

PubMed

Azevedo, L D; Stucchi, R S; de Ataíde, E C; Boin, I F S F

2015-05-01

Graft dysfunction after liver transplantation is a serious complication that can lead to graft loss and patient death. This was a study to identify risk factors for early death (up to 30 days after transplantation). It was an observational and retrospective analysis at the Liver Transplantation Unit, Hospital de Clinicas, State University of Campinas, Brazil. From July 1994 to December 2012, 302 patients were included (>18 years old, piggyback technique). Of these cases, 26% died within 30 days. For analysis, Student t tests and chi-square were used to analyze receptor-related (age, body mass index, serum sodium, graft dysfunction, Model for End-Stage Liver Disease score, renal function, and early graft dysfunction [EGD type 1, 2, or 3]), surgery (hot and cold ischemia, surgical time, and units of packed erythrocytes [pRBC]), and donor (age, hypotension, and brain death cause) factors. Risk factors were identified by means of logistic regression model adjusted by the Hosmer-Lemeshow test with significance set at P < .05. We found that hyponatremic recipients had a 6.26-fold higher risk for early death. There was a 9% reduced chance of death when the recipient serum sodium increased 1 unit. The chance of EGD3 to have early death was 18-fold higher than for EGD1 and there was a 13% increased risk for death for each unit of pRBC transfused. Donor total bilirubin, hyponatremia, massive transfusion, and EGD3 in the allocation graft should be observed for better results in the postoperative period. Copyright © 2015 Elsevier Inc. All rights reserved.

Extracorporeal membrane oxygenation support and post-heart transplant outcomes among United States adults.

PubMed

Zalawadiya, Sandip; Fudim, Marat; Bhat, Geetha; Cotts, William; Lindenfeld, JoAnn

2017-01-01

Patients supported with extracorporeal membrane oxygenation (ECMO) are given priority listing status for heart transplant (HT). Data on post-HT outcomes for adults with ECMO support at the time of HT are limited. We analyzed data from the United Network for Organ Registry (UNOS) registry for 157 ECMO-supported adults (age ≥ 18 years) undergoing HT after January 1, 2000. Data at the time of HT were examined for their association with post-transplant mortality using multivariable Cox proportional hazard analyses. Patients (69.4% males; mean age, 46.0 ± 15.6 years; 15.9% African Americans) were monitored for median of 0.55 years (interquartile range, 0.04-4.5). Seventy patients (44.6%) died during follow-up (survival at 1 year was 57.8%), of which 43 (61.4%) died within 30 days post-HT. For patients surviving the first 30 days after transplant, long-term survival was acceptable (82.3% at 1 year and 76.2% at 5 years). Prevalence of immediate post-HT complications, such as stroke and need for dialysis, were 10.1% and 28.1%, respectively. Post-HT survival did not differ between those who received an allograft before and after January 1, 2009 (univariate hazard ratio, 0.84; 95% confidence interval, 0.51-1.38; p = 0.48). Among the predictors identified for 30-day and long-term mortality were recipient history of renal insufficiency (RI; defined as estimated glomerular filtration rate < 45 ml/min/1.73 m 2 or dialysis) and mechanical ventilation (MV; interaction p < 0.05); those with both MV and RI had significantly poorer post-transplant survival (29.4% and 12.5% for 30-day and 1-year survival, respectively) compared with those without (78.7% and 71.4% for 30-day and 1-year survival, respectively). Post-HT mortality did not change for ECMO-supported adults in the contemporary era, and those with RI and MV had significantly poorer post-transplant survival. A critical review of priority listing status for ECMO-supported patients is warranted for optimal allocation and

Tertiary Excess of Fibroblast Growth Factor 23 and Hypophosphatemia Following Kidney Transplantation

PubMed Central

Seeherunvong, Wacharee; Wolf, Myles

2010-01-01

Hypophosphatemia due to inappropriate urinary phosphate wasting is a frequent metabolic complication of the early period following kidney transplantation. Although previously considered to be caused by tertiary hyperparathyroidism, recent evidence suggests a primary role for persistently elevated circulating levels of the phosphorus-regulating hormone, fibroblast growth factors 23 (FGF23). In the setting of a healthy renal allograft, markedly increased FGF23 levels from the dialysis period induce renal phosphate wasting and inhibition of calcitriol production, which contribute to hypophosphatemia. While such tertiary FGF23 excess and resultant hypophosphatemia typically abates within the first few weeks to months post-transplant, some recipients manifest persistent renal phosphate wasting. Furthermore, increased FGF23 levels have been associated with increased risk of kidney disease progression, cardiovascular disease and death outside of the transplant setting. Whether tertiary FGF23 excess is associated with adverse transplant outcomes is unknown. In this article, we review the physiology of FGF23, summarize its relationship with hypophosphatemia after kidney transplantation, and speculate on its potential impact on long term outcomes of renal allograft recipients. PMID:20946192

Voriconazole-induced periostitis in two post-transplant patients

PubMed Central

Bucknor, Matthew D.; Gross, Andrew J.; Link, Thomas M.

2013-01-01

While drug-related periostitis has been known of for many years, the specific association of diffuse periostitis with voriconazole (most frequently in transplant patients) has only been recently explicitly addressed in the literature. Recognition of the radiologic and clinical manifestations of voriconazole-related periostitis is important for helping to narrow an otherwise broad differential diagnosis. We present two cases that illustrate different radiologic presentations of this painful cause of diffuse periostitis. Case 1 features a 60 year-old woman with a history of orthotopic heart transplant who was hospitalized for “full body pain” with progressively worsening bone tenderness involving the humeri, knees, femurs, hips, and hands. Case 2 describes a 48 year-old man with a history of acute lymphoblastic leukemia status post stem cell transplant who presented with diffuse arthralgias involving bilateral ankles, knees, wrists, and elbows. PMID:24421948

Longitudinal follow-up of nutritional status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation.

PubMed

Urbain, P; Birlinger, J; Lambert, C; Finke, J; Bertz, H; Biesalski, H-K

2013-03-01

There are few longitudinal data on nutritional status and body composition of patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). We assessed nutritional status of 105 patients before alloHCT and its course during the early post-transplant period to day +30 and day +100 via weight history, body mass index (BMI) normalized for gender and age, Subjective Global Assessment, phase angle normalized for gender, age, and BMI, and fat-free and body fat masses. Furthermore, we present a multivariate regression model investigating the impact of factors on body weight. At admission, 23.8% reported significant weight losses (>5%) in the previous 6 months, and we noted 31.5% with abnormal age- and sex-adjusted BMI values (10th, 90th percentiles). BMI decreased significantly (P<0.0001) in both periods by 11% in total, meaning a weight loss of 8.6±5.7 kg. Simultaneously, the patients experienced significant losses (P<0.0001) of both fat-free and body fat masses. Multivariate regression model revealed clinically relevant acute GVHD (parameter estimate 1.43; P=0.02) and moderate/severe anorexia (parameter estimate 1.07; P=0.058) as independent factors influencing early weight loss. In conclusion, our results show a significant deterioration in nutritional status during the early post-transplant period. Predominant alloHCT-associated complications such as anorexia and acute GVHD became evident as significant factors influencing nutritional status.

Growth in pediatric renal transplant recipients.

PubMed

Vasudevan, A; Phadke, K

2007-04-01

One of the fundamental challenges in managing pediatric renal transplant recipient is to ensure normal growth and development. The goal of renal transplant is not just to prolong life but to optimize quality of life. Short stature during childhood may be associated with academic underachievement and development of comorbidities such as attention deficit hyperactivity disorder, learning disability, and mood disorders. The most important factors affecting growth are use of corticosteroids, allograft function, and age and height deficit at the time of transplant. Aggressive conservative management of chronic renal failure and early use of growth hormone therapy will help in optimizing height at time of transplant. Early transplant, steroid minimization or withdrawal, and growth hormone therapy will help in achieving normal adult height in a majority of renal post transplant population. Steroid avoidance to achieve good growth still needs to be validated.

The effect of pre-transplant pain and chronic disease self-efficacy on quality of life domains in the year following hematopoietic stem cell transplantation.

PubMed

O'Sullivan, Madeline L; Shelby, Rebecca A; Dorfman, Caroline S; Kelleher, Sarah A; Fisher, Hannah M; Rowe Nichols, Krista A; Keefe, Francis J; Sung, Anthony D; Somers, Tamara J

2018-04-01

Pain is common for hematopoietic stem cell transplant (HSCT) patients and may be experienced pre-transplant, acutely post-transplant, and for months or years following transplant. HSCT patients with persistent pain may be at risk for poor quality of life following transplant; however, the impact of pre-transplant pain on quality of life post-transplant is not well understood. Self-efficacy for chronic disease management is associated with quality of life among cancer patients and may impact quality of life for HSCT patients. The primary aim was to examine the effect of pre-transplant pain and self-efficacy on quality of life domains in the year following transplant. One hundred sixty-six HSCT patients completed questionnaires providing information on pain, self-efficacy, and quality of life prior to transplant, at discharge, and 3-, 6-, and 12-months post-transplant as part of a longitudinal, observational study. Linear mixed modeling examined the trajectories of these variables and the effect of pre-transplant pain and self-efficacy on post-transplant quality of life. Pain and social and emotional quality of life remained stable in the year following transplant while self-efficacy and physical and functional quality of life improved. Pre-transplant pain was significantly related to lower physical well-being post-transplant. Lower pre-transplant self-efficacy was related to lower quality of life across all domains post-transplant. Above and beyond the effect of pre-transplant pain, self-efficacy for managing chronic disease is important in understanding quality of life following transplant. Identifying patients with pain and/or low self-efficacy pre-transplant may allow for early intervention with self-management strategies.

Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

PubMed

de Oliveira, G L V; Ferreira, A F; Gasparotto, E P L; Kashima, S; Covas, D T; Guerreiro, C T; Brum, D G; Barreira, A A; Voltarelli, J C; Simões, B P; Oliveira, M C; de Castro, F A; Malmegrim, K C R

2017-03-01

Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIM EL , FAS, FASL, A1, BCL2, BCLX L , CFLIP L and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIM EL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8 + Fas + T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIP L and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLX L and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation. © 2016 British Society for Immunology.

Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer.

PubMed

Kusaka, M; Okamoto, M; Takenaka, M; Sasaki, H; Fukami, N; Kataoka, K; Ito, T; Kenmochi, T; Hoshinaga, K; Shiroki, R

2017-06-01

Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract). Nineteen patients were included in this study and a total of 53 gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm. The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison with the general population (1091 ± 63 vs 823 ± 94; P = .0024). The number of genes with altered expression decreased after the induction of mechanistic target of rapamycin (mTOR) inhibitor (1484 ± 227 vs 883 ± 154; P = .0439). No cases of possible digestive cancer were detected in this study period. The gene expression profiling of peripheral blood samples may be a useful and noninvasive diagnostic tool that allows for the early detection of cancer of the digestive system. Copyright © 2017 Elsevier Inc. All rights reserved.

Preoperative Recipient Parameters Allow Early Estimation of Postoperative Outcome and Intraoperative Transfusion Requirements in Liver Transplantation.

PubMed

Schumacher, Carsten; Eismann, Hendrik; Sieg, Lion; Friedrich, Lars; Scheinichen, Dirk; Vondran, Florian W R; Johanning, Kai

2018-01-01

Liver transplantation is a complex intervention, and early anticipation of personnel and logistic requirements is of great importance. Early identification of high-risk patients could prove useful. We therefore evaluated prognostic values of recipient parameters commonly available in the early preoperative stage regarding postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. All adult patients undergoing first liver transplantation at Hannover Medical School between January 2005 and December 2010 were included in this retrospective study. Demographic, clinical, and laboratory data as well as clinical courses were recorded. Prognostic values regarding 30- and 90-day outcomes were evaluated by uni- and multivariate statistical tests. Identified risk parameters were used to calculate risk scores. There were 426 patients (40.4% female) included with a mean age of 48.6 (11.9) years. Absolute 30-day mortality rate was 9.9%, and absolute 90-day mortality rate was 13.4%. Preoperative leukocyte count >5200/μL, platelet count <91 000/μL, and creatinine values ≥77 μmol/L were relevant risk factors for both observation periods ( P < .05, respectively). A score based on these factors significantly differentiated between groups of varying postoperative outcomes and intraoperative transfusion requirements ( P < .05, respectively). A score based on preoperative creatinine, leukocyte, and platelet values allowed early estimation of postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. Results might help to improve timely logistic and personal strategies.

Does recipient work status pre-transplant affect post-heart transplant survival? A United Network for Organ Sharing database review.

PubMed

Ravi, Yazhini; Lella, Srihari K; Copeland, Laurel A; Zolfaghari, Kiumars; Grady, Kathleen; Emani, Sitaramesh; Sai-Sudhakar, Chittoor B

2018-05-01

Recipient-related factors, such as education level and type of health insurance, are known to affect heart transplantation outcomes. Pre-operative employment status has shown an association with survival in abdominal organ transplant patients. We sought to evaluate the effect of work status of heart transplant (HTx) recipients at the time of listing and at the time of transplantation on short- and long-term survival. We evaluated the United Network for Organ Sharing (UNOS) registry for all adult HTx recipients from 2001 to 2014. Recipients were grouped based on their work status at listing and at heart transplantation. Kaplan-Meier estimates illustrated 30-day, 1-year, 5-year, and 10-year survival comparing working with non-working groups. The Cox proportional hazards regression model was applied to adjust for covariates that could potentially confound the post-transplantation survival analysis. Working at listing for HTx was not significantly associated with 30-day and 1-year survival. However, 5- and 10-year mortality were 14.5% working vs 19.8% not working (p < 0.0001) and 16% working vs 26% not working (p < 0.0001), respectively. Working at HTx appeared to be associated with a survival benefit at every time interval, with a trend toward improved survival at 30 days and 1 year and a significant association at 5 and 10 years. Kaplan-Meier analysis demonstrated a 5% and 10% decrease in 5- and 10-year mortality, respectively, for the working group compared with the group not working at transplantation. The Cox proportional hazards regression model showed that working at listing and working at transplantation were each associated with decreased mortality (hazard ratio [HR] = 0.8, 95% confidence interval [CI] 0.71 to 0.91; and HR = 0.76, 95% CI 0.65 to 0.89, respectively). This study is the first analysis of UNOS STAR data on recipient work status pre-HTx demonstrating: (1) an improvement in post-transplant survival for working HTx candidates; and (2

No association between infections, HLA type and other transplant-related factors and risk of cutaneous squamous cell carcinoma in solid organ transplant recipients.

PubMed

Ingvar, Åsa; Ekström Smedby, Karin; Lindelöf, Bernt; Fernberg, Pia; Bellocco, Rino; Tufveson, Gunnar; Höglund, Petter; Adami, Johanna

2012-11-01

Recipients of solid organ transplants are at a markedly increased risk of cutaneous squamous cell carcinoma (SCC). We investigated potential associations between post-transplant infections, HLA type, and other transplant-related factors and risk of SCC, taking immuno-suppressive treatment into account. A population-based case-control study was conducted. All patients who developed SCC during follow-up (1970-1997) were eligible as cases (n = 207). Controls (n = 189) were individually matched to the cases on age and calendar period of transplantation. Detailed exposure information was collected through an extensive, blinded review of medical records. Odds ratios were computed with conditional logistic regression. There were no significant associations with any infectious agents, or with number and timing of infections, specific HLA-type, donor characteristics, or other transplant characteristics and risk of post-transplant SCC. These results suggest that risk of post-transplant SCC is neither closely related to specific post-transplant infectious disorders, nor to the infectious load or specific HLA types.

Life after a lung transplant: a balance of joy and challenges.

PubMed

Graarup, Jytte; Mogensen, Elin Lindberg; Missel, Malene; Berg, Selina Kikkenborg

2017-11-01

psychological challenges after lung transplantation. Several areas call for interventions from healthcare professionals during the early post-transplant period. © 2017 John Wiley & Sons Ltd.

Memory B lymphocytes determine repertoire oligoclonality early after haematopoietic stem cell transplantation

PubMed Central

OMAZIC, B; LUNDKVIST, I; MATTSSON, J; PERMERT, J; NÄSMAN-BJÖRK, I

2003-01-01

The objective of this study was to investigate if oligoclonality of the Ig repertoire post-haematopoietic stem cell transplantation (HSCT) is restricted to memory B lymphocytes or if it is a general property among B lymphocytes. As a measure of B lymphocyte repertoire diversity, we have analysed size distribution of polymerase chain reaction (PCR) amplified Ig H complementarity determining region 3 (CDR3) in naive and memory B lymphocytes isolated from patients before HSCT and at 3, 6 and 12 months after HSCT as well as from healthy controls. We demonstrate a limited variation of the IgH CDR3 repertoire in the memory B lymphocyte population compared to the naive B cell population. This difference was significant at 3 and 6 months post-HSCT. Compared to healthy controls there is a significant restriction of the memory B lymphocyte repertoire at 3 months after HSCT, but not of the naive B lymphocyte repertoire. Twelve months after HSCT, the IgH CDR3 repertoire in both memory and naive B lymphocytes are as diverse as in healthy controls. Thus, our findings suggest a role for memory B cells in the restriction of the oligoclonal B cell repertoire observed early after HSCT, which may be of importance when considering reimmunization of transplanted patients. PMID:12974769

Predicting Post-transplant Recurrence of IgA Nephropathy: The Importance of Crescents

PubMed Central

Avasare, Rupali S.; Rosenstiel, Paul E.; Zaky, Ziad S.; Tsapepas, Demetra; Appel, Gerald B.; Markowitz, Glen S.; Bomback, Andrew S.; Canetta, Pietro A.

2017-01-01

Background Most studies assessing the predictors of recurrent IgA nephropathy in the renal allograft have focused on post-transplant features. Identifying high risk pre-transplant features of IgA nephropathy is useful for counseling patients and may help tailor immunosuppression post-transplant. Methods We investigated the pre-transplant clinical and biopsy features of 62 patients with IgAN who received transplants at Columbia University Medical Center from 2001 to 2012 and compared the characteristics and outcomes of patients with IgAN recurrence to those without recurrence. The primary outcome was time to recurrent IgAN. Secondary outcomes were a composite of doubling of creatinine or allograft failure, and recurrent IgAN as a cause of allograft dysfunction. Results Of the 62 patients, 14 had recurrent IgAN in the allograft. Mean time to recurrence was 2.75 years. Those with recurrent disease were younger at time of native kidney biopsy (29 years vs. 41 years, P < 0.0009). Black race and Hispanic ethnicity composed a higher proportion of the recurrent disease group. On multivariable analysis, significant predictors of recurrent IgAN included age at diagnosis (HR 0.911, 95% CI 0.85 to 0.98), burden of crescents on native biopsy (HR 1.21 per 10% increase in crescents, 95% CI 1.00 to 1.47), and allograft rejection (HR 3.59, 95% CI 1.10 to 11.7) Conclusions Features of native IgAN can help predict the risk of recurrent disease in the renal allograft. In particular, immunologically active disease represented by earlier age of onset and greater burden of crescents on native biopsy is more likely to recur post-transplant. PMID:28056461

[Early human transplants: 60th anniversary of the first successful kidney transplants].

PubMed

Gentili, Marc E

2015-11-01

First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Sequential kidney/islet transplantation using prednisone-free immunosuppression.

PubMed

Kaufman, Dixon B; Baker, Marshall S; Chen, Xiaojuan; Leventhal, Joseph R; Stuart, Frank P

2002-08-01

Islet transplantation is becoming established as a treatment option for type I diabetes in select patients. Individuals with type I diabetes who have previously received a successful kidney allograft may be good candidates for islet transplantation. They have already assumed the risks of chronic immunosuppression, so the added procedural risk of a subsequent islet transplant would be minimal. Furthermore, because of the preimmunosuppressed state it is possible that islet-after-kidney transplantation may result in a more efficient early islet engraftment. Consequently, insulin independence might be achieved with significantly fewer islets than the approximately 8-10,000 islet equivalents/kg/b.w. currently required. A mass that usually demands two or more cadaveric donors. A case of successful islet-after-kidney transplantation is described using the steroid-free Edmonton immunosuppression protocol. Characteristics of the final islet product are: a) islet equivalents: 265,888 (4100 islet equivalents/kg/b.w.); b) islet purity: 75-80%; c) viability: >95% (trypan blue exclusion); and d) mean islet potency (static low-high glucose challenge): 4.16 +/- 1.91-fold increase. Post-transplant the patient's hypoglycemic episodes abated. Exogenous insulin requirements were eliminated at week 12 post-transplant as basal and Ensure (Abbott Laboratories, Abbott Park, IL, USA) oral glucose stimulated C-peptide levels peaked and stabilized. Twenty-four-hour continuous glucose monitoring confirmed moment-to-moment glycemic control, and periodic nonfasting finger stick glucose determinations over the next month confirmed glycemia was controlled. Hemoglobin A1c levels declined from a pretransplant level of 6.9% to 5.3%. Renal allograft function remained changed.

Clinical predictors and outcome implications of early readmission in lung transplant recipients.

PubMed

Osho, Asishana A; Castleberry, Anthony W; Yerokun, Babatunde A; Mulvihill, Michael S; Rucker, Justin; Snyder, Laurie D; Davis, Robert D; Hartwig, Matthew G

2017-05-01

The purpose of this study was to identify risk factors and outcome implications for 30-day hospital readmission in lung transplant recipients. We conducted a retrospective cohort study of lung transplant cases from a single, high-volume lung transplant program between January 2000 and March 2012. Demographic and health data were reviewed for all patients. Risk factors for 30-day readmission (defined as readmission within 30 days of discharge from index lung transplant hospitalization) were modeled using logistic regression, with selection of parameters by backward elimination. The sample comprised 795 patients after excluding scheduled readmissions and in-hospital deaths. Overall 30-day readmission rate was 45.4% (n = 361). Readmission rates were similar across different diagnosis categories and procedure types. By univariate analysis, post-operative complications that predisposed to 30-day readmission included pneumonia, any infection, and atrial fibrillation (all p < 0.05). In the final multivariate model, occurrence of any post-transplant complication was the most significant risk factor for 30-day readmission (odds ratio = 1.764; 95% confidence interval, 1.259-2.470). Even for patients with no documented perioperative complication, readmission rates were still >35%. Kaplan-Meier analysis and multi-variate regression modeling to assess readmission as a predictor of long-term outcomes showed that 30-day readmission was not a significant predictor of worse survival in lung recipients. Occurrence of at least 1 post-transplant complication increases risk for 30-day readmission in lung transplant recipients. In this patient population, 30-day readmission does not predispose to adverse long-term survival. Quality indicators other than 30-day readmission may be needed to assess hospitals that perform lung transplantation. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

How Thinking About the Donor Influences Post-traumatic Growth in Liver Transplant Recipients.

PubMed

Martín-Rodríguez, A; Pérez-San-Gregorio, M Á; Avargues-Navarro, M L; Borda-Mas, M; Pérez-Bernal, J; Gómez-Bravo, M Á

2018-03-01

The aim of this work was to find out whether thinking frequently about the donor influences post-traumatic growth of liver transplant recipients. The sample of 240 patients selected was made up of 185 men and 55 women with an overall mean age of 60.21 (SD 9.3) years. All of them had received liver transplants from cadaver donors. Transplant recipients were asked whether they thought frequently about the donor (yes or no) and filled out the Post-traumatic Growth Inventory. The t test for unpaired samples was applied to analyze how thinking frequently about the donor or not influenced post-traumatic growth. We also calculated the effect sizes by means of Cohen d or Cohen w depending on the nature of the variables analyzed (quantitative or qualitative). The liver transplant recipients who thought frequently about the donor, compared with those who did not, had higher total scores on post-traumatic growth (P = .000; d = 0.57; medium effect size). Furthermore, considering the effect sizes, the differences between the subgroups were more relevant on the following subscales: new possibilities (P = .000; d = 0.53; medium effect size), appreciation of life (P = .000; d = 0.60; medium effect size), and spiritual change (P = .000; d = 0.54; medium effect size). Patients who think frequently about the donor have more post-traumatic growth than those who do not. Copyright © 2017 Elsevier Inc. All rights reserved.

Anatomy in Cologne--Institutional development and body supply from the Weimar Republic to the early post-war period.

PubMed

Kaiser, Stephanie; Gross, Dominik

2015-07-01

The Anatomical Institute of the University of Cologne was founded in 1925. This paper highlights its institutional development and the sources from which it procured bodies for dissection. A comparison is drawn between the first years of the institute's existence during the Weimar Republic (1925-1932) and its rebuilding after war damage in the early post-war period (1947-1954). The institute and its procurement of bodies have not previously been investigated for these two time periods. The Third Reich, for which a detailed study already exists, will be mentioned as well to allow better evaluation of the periods before and after National Socialism. Based on newly evaluated archival material and body journals which will be examined both quantitatively and qualitatively, it becomes apparent that the Cologne institute experienced a chronic shortage of bodies both during the Weimar Republic and the first post-war decade (even though the delivery facilities were mostly the same). However, the situation of the institute in terms of structure, organization and personnel as well as body supply in the aftermath of World War II proved much more challenging than during the time of the Weimar Republic. Copyright © 2015 Elsevier GmbH. All rights reserved.

Rituximab is not a "magic drug" in post-transplant recurrence of nephrotic syndrome.

PubMed

Grenda, Ryszard; Jarmużek, Wioletta; Rubik, Jacek; Piątosa, Barbara; Prokurat, Sylwester

2016-09-01

Pediatric patients with end-stage renal failure due to severe drug-resistant nephrotic syndrome are at risk of rapid recurrence after renal transplantation. Treatment options include plasmapheresis, high-dose of cyclosporine A/methylprednisolone and more recently-rituximab (anti-B CD20 monoclonal depleting antibody). We report five patients with immediate (1-2 days) post-transplant recurrence of nephrotic syndrome, treated with this kind of combined therapy including 2-4 weekly doses of 375 mg/m(2) of rituximab. Only two (of five) patients have showed full long-term remission, while the partial remission was seen in two cases, and no clinical effect at all was achieved in one patient. The correlation between B CD19 cells depletion and clinical effect was present in two cases only. Severe adverse events were present in two patients, including one fatal rituximab-related acute lung injury. The anti-CD20 monoclonal antibody may be not effective in all pediatric cases of rapid post-transplant recurrence of nephrotic syndrome, and benefit/risk ratio must be carefully balanced on individual basis before taking the decision to use this protocol. • nephrotic syndrome may recur immediately after renal transplantation • plasmapheresis combined with pharmacotherapy is used as rescue management • rituximab was reported as effective drug both in primary and post-transplant nephrotic syndrome What is New: • rituximab may not be effective is several cases of post-transplant nephrotic syndrome due to variety of underlying mechanisms of the disease, which may be or not be responsive to this drug • there may be no correlation between drug-induced depletion of specific B cells and clinical effect; this might suggest B-cell independent manner of rituximab action.

Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

PubMed

Anand, Sarah; Thomas, Samantha; Hyslop, Terry; Adcock, Janet; Corbet, Kelly; Gasparetto, Cristina; Lopez, Richard; Long, Gwynn D; Morris, Ashley K; Rizzieri, David A; Sullivan, Keith M; Sung, Anthony D; Sarantopoulos, Stefanie; Chao, Nelson J; Horwitz, Mitchell E

2017-07-01

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

PubMed

Schaefer, S M; Süsal, C; Opelz, G; Döhler, B; Becker, L E; Klein, K; Sickmüller, S; Waldherr, R; Macher-Goeppinger, S; Schemmer, P; Beimler, J; Zeier, M; Morath, C

2016-02-01

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Soluble CD30 levels in recipients undergoing heart transplantation do not predict post-transplant outcome.

PubMed

Ypsilantis, Efthymios; Key, Timothy; Bradley, J Andrew; Morgan, C Helen; Tsui, Stephen; Parameshwar, Jayan; Taylor, Craig J

2009-11-01

The pre-transplant serum level of soluble CD30 (sCD30), a proteolytic derivative of the lymphocyte surface receptor CD30, has been suggested as a biomarker for immunologic risk after organ transplantation. Pre-transplant serum sCD30 levels were determined in 200 consecutive adult heart transplant recipients undertaken at a single center. Transplant outcome (acute rejection in the first 12 months and patient survival up to 5 years post-transplant) was determined. Patients treated with a left ventricular assist device (LVAD) prior to transplantation (n = 28) had higher levels of sCD30 (median 64 U/ml, range 12 to 112 U/ml) than those (n = 172) with no LVAD (median 36 U/ml, range 1 to 158 U/ml, p < 0.0001). Recipients were categorized according to whether sCD30 levels were "low" (lower quartile, <24 U/ml, n = 50), "intermediate" (24 to 58 U/ml, n = 100) or "high" (upper quartile, >58 U/ml, n = 50). Neither acute rejection nor recipient survival differed according to sCD30 level, with values (mean +/- SEM) of 0.30 +/- 0.04, 0.23 +/- 0.03 and 0.30 +/- 0.05 acute rejection episodes per 100 days in the low, intermediate and high groups, respectively, with recipient survival rates at 1 year of 77.7%, 84.9% and 86% and at 5 years of 73.6%, 67.9% and 75.8%, respectively. Pre-transplant serum sCD30 level does not predict acute allograft rejection or recipient survival after heart transplantation, although sCD30 levels are increased by LVAD, possibly as a result of biomaterial-host immune interaction.

The "Post-Post Period" and Environmental Education Research

ERIC Educational Resources Information Center

McKenzie, Marcia

2005-01-01

Described as "post-experimental" and of the "post-post period," the current moment in social science research is typified by multi-voiced texts, researcher reflexivity, cultural criticism, and experimental works; characteristics in keeping with post-structurally informed understandings of social science research as contingent, evolving and messy.…

Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study

PubMed Central

D'Souza, Anita; Dispenzieri, Angela; Wirk, Baldeep; Zhang, Mei-Jie; Huang, Jiaxing; Gertz, Morie A.; Kyle, Robert A.; Kumar, Shaji; Comenzo, Raymond L.; Peter Gale, Robert; Lazarus, Hillard M.; Savani, Bipin N.; Cornell, Robert F.; Weiss, Brendan M.; Vogl, Dan T.; Freytes, César O.; Scott, Emma C.; Landau, Heather J.; Moreb, Jan S.; Costa, Luciano J.; Ramanathan, Muthalagu; Callander, Natalie S.; Kamble, Rammurti T.; Olsson, Richard F.; Ganguly, Siddhartha; Nishihori, Taiga; Kindwall-Keller, Tamila L.; Wood, William A.; Mark, Tomer M.; Hari, Parameswaran

2015-01-01

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality

Early post-natal neuroactive steroid manipulation modulates ondansetron effects on initial periods of alcohol consumption in rats.

PubMed

Bartolomé, Iris; Llidó, Anna; Darbra, Sònia; Pallarès, Marc

2018-06-21

Neuroactive steroids (NS) such as allopregnanolone are crucial for brain development and adult behaviour. Early post-natal alterations of NS by administering finasteride induce a decrease in the sensitivity to stimulant effects of low alcohol doses, an increase in alcohol consumption, and a decrease in ventrostriatal dopamine and serotonin levels. The aim of the present study is to observe if the effects of the 5HT3 receptor antagonist ondansetron on initial alcohol consumption are modulated by post-natal NS manipulation. For this purpose, allopregnanolone, finasteride, or vehicle was injected from day 5 to 9. In adulthood, a novel object preference test was carried out in order to detect a possible novelty-seeking pattern in our animals, which has been related to vulnerability to drug abuse. The subjects then had access to two bottles (alcohol or control solutions) one hour daily for two consecutive weeks. Ondansetron (0.01 mg/kg, 0.1 mg/kg or vehicle) was administered before the hour of consumption in the initial phase (days 1, 2, 3) of the procedure, and after prolonged alcohol intake (days 11, 12, 13). Results indicated that finasteride animals showed a higher preference to explore the new object, as well as a higher alcohol consumption than the rest of the groups. Moreover, 0.1 mg/kg of ondansetron decreased alcohol consumption, but only in the post-natal finasteride group, suggesting a possible increase in 5HT3 receptor sensitivity in these animals. In conclusion, NS manipulation in crucial stages of development, such as early post-natal periods, seems to play an important role on the effects of ondansetron on alcohol intake and in the vulnerability to develop drug use or abuse. Copyright © 2018. Published by Elsevier Inc.

The impact of patient education and psychosocial supports on return to normalcy 36 months post-kidney transplant.

PubMed

Wilkins, Freda; Bozik, Karen; Bennett, Katherine

2003-01-01

Improvements in immunosuppression, and expansion of immunosuppression coverage by Medicare now necessitate beginning to define success in transplantation from a holistic or whole person approach rather than the historical emphasis on patient and graft survival alone. In a new transplant environment, efforts will have to be made to redefine practice so that kidney transplant recipients are prepared for 10 or more years of life with a transplanted graft. Currently, 83% of transplanted patients will never return to work. The purpose of this study is to determine how targeted education and specific psychosocial supports affect the transplant patient's return to normalcy 36 months after kidney transplant. Normalcy is defined as age and socially appropriate activities for that patient. This is a synopsis of a 1-year cross-sectional study of 51 patients who received kidney transplants in 1999 at or near their 36-month anniversary date. Thirty-six months was chosen because this is the date when most patients will lose their Medicare coverage for immunosuppression. In 1999, a multidisciplinary plan was initiated to restructure the transplant recipient evaluation process, such that education about kidney transplantation and expectations for return to normalcy were addressed at the initial 'introduction to transplant session'. These measures were then consistently reinforced with each subsequent contact. At the second contact, written verbal plans for medication purchase and return to normalcy were identified. The team made a conscious effort to develop relationships with the recipients and their significant others, with the intention to better empower them to return to normalcy post-transplant. These measures (education and psychosocial support) were this study's independent variables. At 36 months, all patients were contacted by telephone and a 12-item questionnaire was administered. The questionnaire sought information about the study's dependent variables - employment and

Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

PubMed

Wadei, H M; Lee, D D; Croome, K P; Mai, M L; Golan, E; Brotman, R; Keaveny, A P; Taner, C B

2016-03-01

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013.

PubMed

Fosby, Bjarte; Melum, Espen; Bjøro, Kristian; Bennet, William; Rasmussen, Allan; Andersen, Ina Marie; Castedal, Maria; Olausson, Michael; Wibeck, Christina; Gotlieb, Mette; Gjertsen, Henrik; Toivonen, Leena; Foss, Stein; Makisalo, Heikki; Nordin, Arno; Sanengen, Truls; Bergquist, Annika; Larsson, Marie E; Soderdahl, Gunnar; Nowak, Greg; Boberg, Kirsten Muri; Isoniemi, Helena; Keiding, Susanne; Foss, Aksel; Line, Pål-Dag; Friman, Styrbjörn; Schrumpf, Erik; Ericzon, Bo-Göran; Höckerstedt, Krister; Karlsen, Tom H

2015-06-01

The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004-2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).

Immunizations in solid organ and hematopoeitic stem cell transplant patients: A comprehensive review

PubMed Central

L'Huillier, Arnaud G; Kumar, Deepali

2015-01-01

The Solid Organ Transplantation (SOT) and Haematopoietic Stem Cell Transplantation (HSCT) population is continuously increasing as a result of broader indications for transplant and improved survival. Infectious diseases, including vaccine-preventable diseases, are a significant threat for this population, primarily after but also prior to transplantation. As a consequence, clinicians must ensure that patients are optimally immunized before transplantation, to provide the best protection during the early post-transplantation period, when immunosuppression is the strongest and vaccine responses are poor. After 3–6 months, inactivated vaccines immunization can be resumed. By contrast, live-attenuated vaccines are lifelong contraindicated in SOT patients, but can be considered in HSCT patients at least 2 years after transplantation, if there is no immunosuppression or graft-versus-host-disease. However, because of the advantages of live-attenuated over inactivated vaccines - and also sometimes the absence of an inactivated alternative - an increasing number of prospective studies on live vaccine immunization after transplantation are performed and give new insights about safety and immunogenicity in this population. PMID:26291740

Lung transplantation for lymphangioleiomyomatosis: the European experience.

PubMed

Benden, Christian; Rea, Federico; Behr, Jürgen; Corris, Paul A; Reynaud-Gaubert, Martine; Stern, Marc; Speich, Rudolf; Boehler, Annette

2009-01-01

Lung transplantation has been accepted widely as therapy for end-stage pulmonary lymphangioleiomyomatosis (LAM); however, single-center and national experience is limited due to the rarity of LAM. We report the recent European experience of lung transplantation for LAM. A self-administered questionnaire was distributed to 30 European lung transplant centers to evaluate patients who underwent primary lung transplantation for LAM (1997 to 2007). Seventy percent of centers responded to the questionnaire. A total of 61 lung transplants were undertaken in women only, with mean age at transplant 41.3 years (SD 5.1). Centers performed a median of 2 (0 to 9) transplant operations. Severe pleural adhesions were the most common intra-operative complication. Early deaths (N = 6) were due to primary graft or multiple-organ failure or sepsis. Twelve recipients were diagnosed with bronchiolitis obliterans syndrome at a median of 20 months (range 10 to 86 months) post-transplant. LAM-related complications included renal angiomyolipoma and pneumothorax in the native lung. Recurrence of LAM occurred in 4 recipients. As of December 2007, actuarial Kaplan-Meier survival was 79% at 1 year and 73% at 3 years post-transplant. Post-transplant outcome for pulmonary LAM in the recent era appears to have improved compared with the previous era. LAM-related complications remain common, but recurrence of LAM in the allograft is rare.

Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease.

PubMed

Kawaguchi, Yoshikuni; Sugawara, Yasuhiko; Akamatsu, Nobuhisa; Kaneko, Junichi; Tanaka, Tomohiro; Tamura, Sumihito; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

2014-11-27

Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.

Post-autologous transplant maintenance therapies in lymphoid malignancies: are we there yet?

PubMed

Epperla, N; Fenske, T S; Lazarus, H M; Hamadani, M

2015-11-01

Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post-auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5- and 10-year PFS rates are ~60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT.

Post-transplant monitoring of soluble CD30 level as predictor of graft outcome: a single center experience from China.

PubMed

Wang, Dong; Wu, Weizhen; Yang, Shunliang; Wang, Qinghua; Tan, Jianming

2012-12-01

There are no reliable parameters for post-transplantation immunological monitoring, which might enable recipient-tailored immunosuppressive therapy. 250 renal graft recipients were enrolled and detected for sCD30 level pre-transplantation, and on days 5 and 14, and on months 1, 3, 6, 12, 24, 36, 48 and 60 post-transplantation. Analysis was performed on correlation between sCD30 level and acute rejection, lung infection, or graft loss respectively. sCD30 levels descended to a nadir with a mean of 10.2 ± 3.8 U/mL on day 30 post-transplantation, then rose gradually, and approached 21.8 ± 10.1 U/mL on month 3, 34.2 ± 16.5 U/mL on month 6, and 42.9 ± 29.5 U/mL on month 12, then presented a stable level. Recipients with AR had significantly higher sCD30 levels than those without AR on days 5 and 14 post-transplantation. Recipients with pneumonia had significantly lower sCD30 levels within 3 months post-transplantation than those without pneumonia. Significantly higher sCD30 levels were recorded in recipients who suffered graft loss than those with normal graft function on days 5 and 14, and on months 6, 12, and 24. High sCD30 level (≥ 48.3 U/mL) at month 12 post-transplantation has an obvious detrimental effect on renal graft survival (p=0.000, HR=9.075). Serum sCD30 level might reflect immune state of renal graft recipients. Post-transplantation sequential monitoring of sCD30 level is necessary, which might not only identify recipients at the risk of acute rejection and graft loss, but also chosen as an independent predictor of pneumonia in renal transplant recipients. Copyright © 2012 Elsevier B.V. All rights reserved.

Physical activity levels early after lung transplantation.

PubMed

Wickerson, Lisa; Mathur, Sunita; Singer, Lianne G; Brooks, Dina

2015-04-01

Little is known of the early changes in physical activity after lung transplantation. The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population. This was a prospective cohort study. Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire). Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=-.48, P=.007), daily steps (r=-.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=-.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps. Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study. Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise

Influence of Transplant Center Procedural Volume on Survival Outcomes of Heart Transplantation for Children Bridged with Mechanical Circulatory Support.

PubMed

Hsieh, Alex; Tumin, Dmitry; McConnell, Patrick I; Galantowicz, Mark; Tobias, Joseph D; Hayes, Don

2017-02-01

Transplant center expertise improves survival after heart transplant (HTx) but it is unknown whether center expertise ameliorates risk associated with mechanical circulatory support (MCS) bridge to transplantation. This study investigated whether center HTx volume reduced survival disparities among pediatric HTx patients bridged with extracorporeal membrane oxygenation (ECMO), left ventricular assist device (LVAD), or no MCS. Patients ≤18 years of age receiving first-time HTx between 2005 and 2015 were identified in the United Network of Organ Sharing registry. Center volume was the total number of HTx during the study period, classified into tertiles. The primary outcome was 1 year post-transplant survival, and MCS type was interacted with center volume in Cox proportional hazards regression. The study cohort included 4131 patients, of whom 719 were supported with LVAD and 230 with ECMO. In small centers (≤133 HTx over study period), patients bridged with ECMO had increased post-transplant mortality hazard compared to patients bridged with LVAD (HR 0.29, 95% CI 0.12, 0.71; p = 0.006) and patients with no MCS (HR 0.33, 95% CI 0.19, 0.57; p < 0.001). Interactions of MCS type with medium or large center volume were not statistically significant, and the same differences in survival by MCS type were observed in medium- or large-volume centers (136-208 or ≥214 HTx over the study period). Post-HTx survival disadvantage of pediatric patients bridged with ECMO persisted regardless of transplant program volume. The role of institutional ECMO expertise outside the transplant setting for improving outcomes of ECMO bridge to HTx should be explored.

Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score.

PubMed

Kalafateli, Maria; Mantzoukis, Konstantinos; Choi Yau, Yan; Mohammad, Ali O; Arora, Simran; Rodrigues, Susana; de Vos, Marie; Papadimitriou, Kassiani; Thorburn, Douglas; O'Beirne, James; Patch, David; Pinzani, Massimo; Morgan, Marsha Y; Agarwal, Banwari; Yu, Dominic; Burroughs, Andrew K; Tsochatzis, Emmanuel A

2017-02-01

Although malnutrition and sarcopenia are prevalent in cirrhosis, their impact on outcomes following liver transplantation is not well documented. The associations of nutritional status and sarcopenia with post-transplant infections, requirement for mechanical ventilation, intensive care (ICU) and hospital stay, and 1 year mortality were assessed in 232 consecutive transplant recipients. Nutritional status and sarcopenia were assessed using the Royal Free Hospital-Global Assessment (RFH-GA) tool and the L3-psoas muscle index (L3-PMI) on CT, respectively. A wide range of RFH-SGA and L3-PMI were observed within similar Model for End-stage Liver Disease (MELD) sub-categories. Malnutrition and sarcopenia were independent predictors of all outcomes. Post-transplant infections were associated with MELD (OR = 1.055, 95%CI = 1.002-1.11) and severe malnutrition (OR = 6.55, 95%CI = 1.99-21.5); ventilation > 24 h with MELD (OR = 1.1, 95%CI = 1.036-1.168), severe malnutrition (OR = 8.5, 95%CI = 1.48-48.87) and suboptimal donor liver (OR = 2.326, 95%CI = 1.056-5.12); ICU stay > 5 days, with age (OR = 1.054, 95%CI = 1.004-1.106), MELD (OR = 1.137, 95%CI = 1.057-1.223) and severe malnutrition (OR = 7.46, 95%CI = 1.57-35.43); hospital stay > 20 days with male sex (OR = 2.107, 95%CI = 1.004-4.419) and L3-PMI (OR = 0.996, 95%CI = 0.994-0.999); 1 year mortality with L3-PMI (OR = 0.996, 95%CI = 0.992-0.999). Patients at the lowest L3-PMI receiving suboptimal grafts had longer ICU/hospital stay and higher incidence of infections. Malnutrition and sarcopenia are associated with early post-liver transplant morbidity/mortality. Allocation indices do not include nutritional status and may jeopardize outcomes in nutritionally compromised individuals.

Development of models to predict early post-transplant recurrence of hepatocellular carcinoma that also integrate the quality and characteristics of the liver graft: A national registry study in China.

PubMed

Ling, Qi; Liu, Jimin; Zhuo, Jianyong; Zhuang, Runzhou; Huang, Haitao; He, Xiangxiang; Xu, Xiao; Zheng, Shusen

2018-04-27

Donor characteristics and graft quality were recently reported to play an important role in the recurrence of hepatocellular carcinoma after liver transplantation. Our aim was to establish a prognostic model by using both donor and recipient variables. Data of 1,010 adult patients (training/validation: 2/1) undergoing primary liver transplantation for hepatocellular carcinoma were extracted from the China Liver Transplant Registry database and analyzed retrospectively. A multivariate competing risk regression model was developed and used to generate a nomogram predicting the likelihood of post-transplant hepatocellular carcinoma recurrence. Of 673 patients in the training cohort, 70 (10.4%) had hepatocellular carcinoma recurrence with a median recurrence time of 6 months (interquartile range: 4-25 months). Cold ischemia time was the only independent donor prognostic factor for predicting hepatocellular carcinoma recurrence (hazard ratio = 2.234, P = .007). The optimal cutoff value was 12 hours when patients were grouped according to cold ischemia time at 2-hour intervals. Integrating cold ischemia time into the Milan criteria (liver transplantation candidate selection criteria) improved the accuracy for predicting hepatocellular carcinoma recurrence in both training and validation sets (P < .05). A nomogram composed of cold ischemia time, tumor burden, differentiation, and α-fetoprotein level proved to be accurate and reliable in predicting the likelihood of 1-year hepatocellular carcinoma recurrence after liver transplantation. Additionally, donor anti-hepatitis B core antibody positivity, prolonged cold ischemia time, and anhepatic time were linked to the intrahepatic recurrence, whereas older donor age, prolonged donor warm ischemia time, cold ischemia time, and ABO incompatibility were relevant to the extrahepatic recurrence. The graft quality integrated models exhibited considerable predictive accuracy in early hepatocellular carcinoma recurrence risk

Annual literature review of donor-specific HLA antibodies after organ transplantation.

PubMed

Kaneku, Hugo

2011-01-01

The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

A simple method to treat post-kydney transplantation lymphocele.

PubMed

Damiano, G; Lombardo, C; Palumbo, V D; Buffa, D; Maione, C; Gioviale, M C; Cacciabaudo, F; Spinelli, G; Calvagna, C; Lo Monte, A I

2011-01-01

To describe our experience with ultrasonic-guided instillation of povidone-iodine to treat post-kidney transplantation lymphocele. Patients and methods. We studied the safety and efficacy of this procedure for treatment of lymphocele in 6 male kidney transplanted recipients in which we assisted a progressive increase of creatinine and urinary proteins levels and color-Doppler ultrasonography demonstrated an increase (25,4%) of index of resistence (IR) Using eco-colorDoppler, the related-graft lymphocele location and the distance to the anterior abdominal wall were determined; then, a radiopaque double-lumen catheter was used to instillate 5% povidone-iodine 10 ml. Results. Percutaneous drainage achieved a resolution rate of 100%. Studying the rate of peripheral and internal vascularization of the kidney before and after treatment, eco-colorDoppler showed a significant decrease of the IR (24,6%). Conclusions. The US-guided povidone-iodine instillation for treatment of lymphocele following renal transplantation may be considered as first choice therapy in such disease.

Parents' education level and mortality and morbidity of children after liver transplantation.

PubMed

Bahador, Z; Dehghani, S M; Bahador, A; Nikeghbalian, S; Hafezi, N; Bahador, M; Malek-Hosseini, S A

2015-01-01

So far numerous post-transplant outcome predictors have been studied to decrease the loss of resources and grafts after organ transplantation. The role of education, as a predictor, in liver transplantation outcome has so far been studied in several articles. However, in most of the studies it was evaluated as a surrogate for socioeconomic status or other variants. The absolute impact of parents' education has rarely been studied. Adult patients are their own caregivers whereas pediatric liver transplantation recipients are mostly cared by their parents. To evaluate the effect of level of patients' education on the mortality and morbidity of pediatric liver transplant recipients. We studied a group of 91 children who had undergone liver transplantation in our center from March 21, 2012 to July 21, 2013. In this retrospective study, patients' medical charts and questionnaire were used to collect the necessary data. Post-transplantation mortality and complications were divided into two categories: Early (<6 months after liver transplantation), and late (≥6 months after the transplantation). Parents' educational level was also categorized into 5 groups. Multivariate analysis of all groups showed that paternal education is an independent predictor of the late post-transplantation complications (p=0.024). Educational level of children's mothers had no significant correlation with the late post-transplantation complications (p=0.45). Neither maternal (p=0.59) nor paternal (p=0.607) education had significant effect on the late post-transplantation mortality. Paternal educational level of liver transplanted children is associated with the late post-transplantation complications.

Effects of an early referral system on liver transplantation for hepatoblastoma at Texas Children's Hospital.

PubMed

Kueht, Michael; Thompson, Patrick; Rana, Abbas; Cotton, Ronald; O'Mahony, Christine; Goss, John

2016-06-01

The purposes of this study were to analyze the effects of an ERS on time to transplantation and to describe our center's experience with OLT for HB. Patients who received OLT for HB between 2000 and 2013 were included. Patient and allograft characteristics, chemotherapy regimens, and prior surgical therapies were examined. The interval between diagnosis and OLT prior to and following the institution of an ERS for transplant was compared. Survival and tumor recurrence were analyzed. Nineteen patients received OLT for HB (mean age 33 months). All children received grafts from deceased donors. Two patients underwent prior resections. Tumor recurred in four patients (21.1%). Both patients who received salvage transplants experienced post-OLT recurrence. Three of the four recurrences occurred in spite of adjuvant chemotherapy. There were three deaths: two from metastatic disease. One- and five-yr survivals were 86.1% and 73.8%. After the institution of the ERS, the mean interval between tissue diagnosis and OLT was significantly reduced. Our series of 19 patients demonstrates a 21% recurrence of HB following OLT despite chemotherapy. Five-yr survival reached 73.8%. A system of early referral can effectively reduce times between diagnosis and transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Therapeutic approach to respiratory infections in lung transplantation.

PubMed

Clajus, Carolina; Blasi, Francesco; Welte, Tobias; Greer, Mark; Fuehner, Thomas; Mantero, Marco

2015-06-01

Lung transplant recipients (LTRs) are at life-long risk for infections and disseminated diseases owing to their immunocompromised state. Besides organ failure and sepsis, infection can trigger acute and chronic graft rejection which increases mortality. Medical prophylaxis and treatment are based on comprehensive diagnostic work-up including previous history of infection and airway colonisation to reduce long-term complications and mortality. Common bacterial pathogens include Pseudomonas and Staphylococcus, whilst Aspergillus and Cytomegalovirus (CMV) are respectively the commonest fungal and viral pathogens. Clinical symptoms can be various in lung transplant recipients presenting an asymptomatic to severe progress. Regular control of infection parameters, daily lung function testing and lifelong follow-up in a specialist transplant centre are mandatory for early detection of bacterial, viral and fungal infections. After transplantation each patient receives intensive training with rules of conduct concerning preventive behaviour and to recognize early signs of post transplant complications. Early detection of infection and complications are important goals to reduce major complications after lung transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of early neurological complications on clinical outcome following lung transplant.

PubMed

Gamez, Josep; Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

2017-01-01

Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

Influence of early neurological complications on clinical outcome following lung transplant

PubMed Central

Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

2017-01-01

Background Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. Methods We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Results Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients’ survival. Conclusions The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors. PMID:28301586

[Post-transplant lymphoproliferative disorder: a clinicopathologic study of 15 cases].

PubMed

Chen, Ding-bao; Wang, Ying; Song, Qiu-jing; Shen, Dan-hua

2012-09-01

To study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD). The clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues. Amongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral

Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.

PubMed

Pochon, Cécile; Oger, Emmanuel; Michel, Gérard; Dalle, Jean-Hugues; Salmon, Alexandra; Nelken, Brigitte; Bertrand, Yves; Cavé, Hélène; Cayuela, Jean-Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Geneviève; Méchinaud, Françoise; Rohrlich, Pierre; Paillard, Catherine; Demeocq, François; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Eliaou, Jean-François; Semana, Gilbert; Drunat, Séverine; Jonveaux, Philippe; Bordigoni, Pierre; Gandemer, Virginie

2015-04-01

Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ≥10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention. © 2014 John Wiley & Sons Ltd.

Necrosis of the femoral head after kidney transplantation.

PubMed

Lausten, G S; Lemser, T; Jensen, P K; Egfjord, M

1998-12-01

We reviewed the medical records of 750 patients (445 men, 305 women), who had received a kidney transplant during the period 1968-1995, for any sign of necrosis of the femoral head. For post-operative immunosuppression, 374 patients had received high-dose corticosteroids (average 12.5 g during the first year post-operatively), while 376 patients had received low-dose corticosteroids (average 6.5 g during the first year post-operatively) and cyclosporin A. Survival curves according to Kaplan and Meier (J Am Stat Ass 1958: 53: 457-481) were constructed. In the high-dose steroid group, 42/374 patients (11.2%) developed femoral head necrosis, at an average of 26.2 months post-transplantation. In the low-dose steroid group, only 19/376 (5.1%) patients developed this complication, at an average of 20.5 months post-transplantation. This difference in numbers of femoral head necroses was highly significant (p < 0.005). We conclude that steroid doses should be minimized whenever feasible in post-transplant immunosuppression therapy.

Cerebral Toxoplasmosis Masquerading Cns Lymphoma on FDG PET-CT in Post Renal Transplant Patient

PubMed Central

Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi; Das, Chandan Jyoti; Shamim, Shamim Ahmed

2017-01-01

20 year old post renal transplant patient developed recurrent episodes of seizure. MRI revealed focal lesion in right parieto-occipital lobe with perilesional edema. FDG PET-CT revealed multiple hypermetabolic lesions in bilateral cerebral hemisphere. Subsequent biopsy from the lesion demonstrated bradyzoites of Toxoplasma gondii with inflammatory cells and thereby, a confirmatory diagnosis of cerebral toxoplasmosis was made. This case demonstrates the fact that increased FDG uptake in cerebral lesions in post transplant patient should be interpreted with caution and confirmed with histopathological correlation. PMID:28533649

Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.

PubMed

Huang, Yihung; Tilea, Anca; Gillespie, Brenda; Shahinian, Vahakn; Banerjee, Tanushree; Grubbs, Vanessa; Powe, Neil; Rios-Burrows, Nilka; Pavkov, Meda; Saran, Rajiv

2017-08-01

Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m 2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m 2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care. Copyright © 2017 by the American Society of Nephrology.

Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide.

PubMed

Bashey, Asad; Zhang, Mei-Jie; McCurdy, Shannon R; St Martin, Andrew; Argall, Trevor; Anasetti, Claudio; Ciurea, Stefan O; Fasan, Omotayo; Gaballa, Sameh; Hamadani, Mehdi; Munshi, Pashna; Al Malki, Monzr M; Nakamura, Ryotaro; O'Donnell, Paul V; Perales, Miguel-Angel; Raj, Kavita; Romee, Rizwan; Rowley, Scott; Rocha, Vanderson; Salit, Rachel B; Solh, Melhem; Soiffer, Robert J; Fuchs, Ephraim Joseph; Eapen, Mary

2017-09-10

Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P < .001) and chronic (HR, 0.35; P < .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up.

Family Caregivers of Liver Transplant Recipients: Coping Strategies Associated With Different Levels of Post-traumatic Growth.

PubMed

Pérez-San-Gregorio, M Á; Martín-Rodríguez, A; Borda-Mas, M; Avargues-Navarro, M L; Pérez-Bernal, J; Gómez-Bravo, M Á

2018-03-01

Analyze the influence of 2 variables (post-traumatic growth and time since liver transplantation) on coping strategies used by the transplant recipient's family members. In all, 218 family members who were their main caregivers of liver transplant recipients were selected. They were evaluated using the Posttraumatic Growth Inventory and the Brief COPE. A 3 × 3 factorial analysis of variance was used to analyze the influence that post-traumatic growth level (low, medium, and high) and time since transplantation (≤3.5 years, >3.5 to ≤9 years, and >9 years) exerted on caregiver coping strategies. No interactive effects between the two factors in the study were found. The only significant main effect was the influence of the post-traumatic growth factor on the following variables: instrumental support (P = .007), emotional support (P = .005), self-distraction (P = .006), positive reframing (P = .000), acceptance (P = .013), and religion (P = <.001). According to the most relevant effect sizes, low post-traumatic growth compared with medium growth was associated with less use of self-distraction (P = .006, d = -0.52, medium effect size), positive reframing (P = .001, d = -0.62, medium effect size), and religion (P = .000, d = -0.66, medium effect size), and in comparison with high growth, it was associated with less use of positive reframing (P = .002, d = -0.56, medium effect size) and religion (P = .000, d = 0.87, large effect size). Regardless of the time elapsed since the stressful life event (liver transplantation), family members with low post-traumatic growth usually use fewer coping strategies involving a positive, transcendent vision to deal with transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical relevance of pre and post-transplant immune markers in kidney allograft recipients: anti-HLA and MICA antibodies and serum levels of sCD30 and sMICA.

PubMed

Solgi, Ghasem; Furst, Daniel; Mytilineos, Joannis; Pourmand, Gholamreza; Amirzargar, Ali Akbar

2012-03-01

This retrospective study aims to determine the prognostic values of HLA and MICA antibodies, serum levels of sCD30 and soluble form of MHC class I related chain A (sMICA) in kidney allograft recipients. Sera samples of 40 living unrelated donor kidney recipients were tested by ELISA and Flow beads techniques for the presence of anti HLA and MICA antibodies and the contents of sCD30 and sMICA. HLA and MICA antibody specification was performed by LABScreen single antigen beads to determine whether the antibodies were directed against donor mismatches. Within first year post operatively 9 of 40 patients (22.5%) showed acute rejection episodes (ARE) that four of them lost their grafts compared to 31 functioning transplants (P=0.001). The presence of HLA antibodies before and after transplantation was significantly associated with ARE (P=0.01 and P=0.02 respectively). Sensitization to HLA class II antigens pre-transplant was strongly associated with higher incidence of ARE (P=0.004). A significant correlation was found between ARE and appearance of non-donor specific antibodies (P=0.02). HLA antibody positive patients either before or after transplantation showed lower graft survival rates than those without antibodies during three years follow-up (P=0.04 and P=0.02). Anti-MICA antibodies were observed in 8/40(20%) and 5/40(12.5%) of patients pre and post-transplant respectively. Coexistence of HLA and MICA antibodies was shown in 2 of 4 cases with graft loss. A significant increased level of sCD30 at day 14 (P=0.001) and insignificant decreased levels of sMICA pre and post operatively were detected in rejecting transplants compared to functioning graft group. Our findings support the view that monitoring of HLA and MICA antibodies as well as sCD30 levels early after transplant has predictive value for early and late allograft dysfunctions and the presence of these factors are detrimental to graft function and survival. Copyright © 2012 Elsevier B.V. All rights

Carbachol improves secretion in the early phase after rabbit submandibular gland transplantation.

PubMed

Shi, L; Cong, X; Zhang, Y; Ding, C; Ding, Q W; Fu, F Y; Wu, L L; Yu, G Y

2010-05-01

To investigate the changes in the muscarinic receptor signaling pathway with submandibular gland (SMG) transplantation and whether carbachol improves secretion in transplanted SMGs. SMG autotransplantation was performed in a rabbit model. Carbachol (1 microM) was infused into the transplanted glands from postoperative day 1-7. The expression of the M1 and M3 muscarinic receptors, aquaporin-5 (AQP5), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by RT-PCR, immunoblotting or immunofluorescence. The content of inositol 1, 4, 5-trisphosphate (IP(3)) was measured by radioimmunoassay. Salivary flow of the transplanted SMGs was decreased after transplantation. As well, the expressions of M1 and M3 receptors and their downstream signaling molecules, IP(3), p-ERK1/2 and AQP5, were all reduced. Atrophy of acinar cells was shown in transplanted glands. However, all these alterations were reversed after carbachol treatment for 7 days. Furthermore, carbachol directly increased the mRNA expression of AQP5 and phosphorylation of ERK1/2 in cultured neonatal rabbit SMG cells. A lack of acetylcholine and downregulation of the muscarinic receptor signaling pathway is involved in the early hypofunction of transplanted SMGs. Carbachol treatment could be a new therapeutic strategy to improve secretion and prevent the obstruction of Wharton's duct in the early phase after SMG transplantation.

Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement.

PubMed

Truong, Dinh Quang; Darwish, Ahmed A; Gras, Jérémie; Wieërs, Grégoire; Cornet, Anne; Robert, Annie; Mourad, Michel; Malaise, Jacques; de Ville de Goyet, Jean; Reding, Raymond; Latinne, Dominique

2007-06-01

Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.

Nutritional status, lipid profile and HOMA-IR in post-liver transplant patients.

PubMed

Da Silva Alves, Vanessa; Hack Mendes, Roberta; Pinto Kruel, Cleber Dario

2014-05-01

A high prevalence of overweight, obesity, diabetes and dyslipidemia has been reported following liver transplantation (LT). Although these conditions are known to induce an increased risk for cardiovascular events, which are among the major causes of death in post-LT patients, much debate remains in the literature regarding the applicability of different nutritional assessments methods to this population. To assess the nutritional status, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR) and dietary intake adequacy in the post-LT period. Cross-sectional study of patients after a maximum of 2 years post-LT, involving the assessment of body mass index (BMI), percent weight loss, arm (AC) and arm muscle circumference (AMC), triceps skinfold (TSF), neck (NC) and waist (WC) circumference, lipid profile, HOMA-IR and percent adequacy of dietary intake. In the group of 36 patients, 61.1% were male, mean age 53.2 years (± 10.6). Severe weight loss was noted in 66.7% of patients. Most individuals were eutrophic according to BMI, AC and AMC, while TSF showed malnutrition, NC demonstrated overweight and WC showed metabolic risk. Dyslipidemia was diagnosed in 87.5% of patients, and insulin resistance in 57% of the patients. Most patients had adequate dietary intake, although the time since transplant was positively correlated with AC (r = 0.353; p = 0.035) and negatively correlated with vitamin A intake (r = - 0.382; p = 0.022), with the caloric adequacy (r = -0.338; p = 0.044) and vitamin A adequacy (r = -0.382; p = 0.021). Although anthropometry provided somewhat variable nutritional diagnoses, when combined with biochemical tests, findings showed the prevalence of cardiovascular risk. As such, patients should be provided with transdisciplinary assistance, and strategies should be developed so as to reduce the risk factors recorded in this population. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

The observational study of selected sexual behaviour issues in female organ transplant recipients.

PubMed

Szpotanska-Sikorska, Monika; Mazanowska, Natalia; Staruch, Monika; Wielgos, Miroslaw; Pietrzak, Bronislawa

2017-06-01

To investigate sexual behaviour in women following solid organ transplantation. A cross-sectional single-centre survey study of 230 female organ transplant recipients, aged 18-45years. Sexual behaviour, contraceptive awareness and methods of birth control. 205 females declared to be post their sexual initiation. The mean age at sexual initiation in our study population was 20.3±3.3years (range: 14-32). Fifty-three percent (122/230) of the patients declared that they had only one sexual partner at enrolment. After transplantation female organ recipients became more sexually active (71% vs. 83%; p=0.018). The frequency of sexual intercourse decreased significantly in the post-transplant period (p=0.004). In the group of sexually active females before transplantation the frequency of sexual intercourses decreased significantly in the post-transplant period (mean Δ -0.16±0.79; p=0.004). An increase or lack of change in the frequency of sexual intercourse was noted amongst younger transplant-recipients (OR: 0.91; 95%CI 0.86-0.97) and women with effective birth control methods post-transplantation (OR: 3.68; 95%CI 1.60-8.49). Sexual education of organ transplant recipients is necessary, mainly in younger patients, who present to be more sexually active, thus they need to be taught about effective family planning. Copyright © 2017 Elsevier B.V. All rights reserved.

Pediatric lung transplantation

PubMed Central

2017-01-01

Pediatric lung transplantation has been undertaken since the 1980s, and it is today considered an accepted therapy option in carefully selected children with end-stage pulmonary diseases, providing carefully selected children a net survival benefit and improved health-related quality of life. Nowadays, >100 pediatric lung transplants are done worldwide every year. Here, specific pediatric aspects of lung transplantation are reviewed such as the surgical challenge, effects of immunosuppression on the developing pediatric immune system, and typical infections of childhood, as it is vital to comprehend that children undergoing lung transplants present a real challenge as children are not ‘just small adults’. Further, an update on the management of the pediatric lung transplant patient is provided in this review, and future challenges outlined. Indications for lung transplantation in children are different compared to adults, the most common being cystic fibrosis (CF). However, the primary diagnoses leading to pediatric lung transplantation vary considerably by age group. Furthermore, there are regional differences regarding the primary indication for lung transplantation in children. Overall, early referral, careful patient selection and appropriate timing of listing are crucial to achieve real survival benefit. Although allograft function is to be preserved, immunosuppressant-related side effects are common in children post-transplantation. Strategies need to be put into practice to reduce drug-related side effects through careful therapeutic drug monitoring and lowering of target levels of immunosuppression, to avoid acute-reversible and chronic-irreversible renal damage. Instead of a “one fits all approach”, tailored immunosuppression and a personalized therapy is to be advocated, particularly in children. Further, infectious complications are a common in children of all ages, accounting for almost 50% of death in the first year post-transplantation

Predicting Post-Transplant Recurrence of IgA Nephropathy: The Importance of Crescents.

PubMed

Avasare, Rupali S; Rosenstiel, Paul E; Zaky, Ziad S; Tsapepas, Demetra S; Appel, Gerald B; Markowitz, Glen S; Bomback, Andrew S; Canetta, Pietro A

2017-01-01

Most studies that have assessed the predictors of recurrent IgA nephropathy (IgAN) in the renal allograft have focused on post-transplant features. Identifying high-risk pre-transplant features of IgAN is useful for counseling patients and may help in tailoring post-transplant immunosuppression. We investigated the pre-transplant clinical and biopsy features of 62 patients with IgAN who received transplants at Columbia University Medical Center from 2001 to 2012 and compared the characteristics and outcomes of patients with IgAN recurrence to those without recurrence. The primary outcome was time to recurrent IgAN. Secondary outcomes were a composite of doubling of creatinine or allograft failure, and recurrent IgAN as a cause of allograft dysfunction. Of the 62 patients, 14 had recurrent IgAN in the allograft. Mean time to recurrence was 2.75 years. Those with recurrent disease were younger at the time of native kidney biopsy (29 vs. 41 years, p < 0.0009). Black race and Hispanic ethnicity composed a higher proportion of the recurrent disease group. On multivariable analysis, significant predictors of recurrent IgAN included age at diagnosis (hazards ratio (HR) 0.911, 95% CI 0.85-0.98), burden of crescents on native biopsy (HR 1.21 per 10% increase in crescents, 95% CI 1.00-1.47) and allograft rejection (HR 3.59, 95% CI 1.10-11.7). Features of native IgAN can help predict the risk of recurrent disease in the renal allograft. In particular, immunologically active disease represented by earlier age of onset and greater burden of crescents on native biopsy is more likely to recur after transplant. © 2017 S. Karger AG, Basel.

Disseminated Mycobacterium bovis infection post-kidney transplant following remote intravesical BCG therapy for bladder cancer.

PubMed

Ziegler, Jennifer; Ho, Julie; Gibson, Ian W; Nayak, Jasmir G; Stein, Markus; Walkty, Andrew; Orr, Pamela

2018-05-29

Intravesical Bacillus Camlette-Guérin (BCG) is the treatment of choice for non-muscle invasive bladder cancer, and has been used successfully for over 40 years. A rare and potentially fatal complication of intravesical BCG therapy is BCG-induced sepsis. We report a rare case in which a patient with end-stage renal disease secondary to chronic granulomatous interstitial nephritis underwent remote, pre-transplant intravesical BCG treatment for high-grade non-invasive papillary bladder carcinoma. The patient subsequently received a deceased donor kidney transplant 5 years after BCG therapy, with thymoglobulin induction therapy and standard triple maintenance immunosuppression. Two years post-transplant, he developed BCG-induced sepsis confirmed by cultures from urine, blood and left native kidney biopsy. He died from disseminated BCG-induced sepsis and failure of his renal allograft. This case highlights the potential adverse reactions associated with intravesical BCG therapy that may occur years after bladder cancer therapy is completed, and should heighten physician awareness for BCG-related infections during pre-transplant assessment and post-transplant care of solid organ transplants recipients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Early Improvement in Marrow Fibrosis Following Haploidentical Stem Cell Transplantation for a Patient with Myelodysplastic Syndrome with Bone Marrow Fibrosis

PubMed Central

Takahashi, Shuichiro; Tsumanuma, Riko; Aizawa, Keiko; Osakabe, Mitsumasa; Maeda, Kunihiko; Omoto, Ejiro

2016-01-01

The prognosis for myelodysplastic syndrome with bone marrow fibrosis (MDS-F) is worse than the prognosis of MDS without fibrosis. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy; however, the indications and the procedures involved in HSCT remain unclear. We herein describe a 69-year-old Japanese man with MDS-F who received haploidentical HSCT and post-transplantation cyclophosphamide. Although the first HSCT resulted in secondary graft failure, the second HSCT using PTCy led to successful engraftment after early improvement in fibrosis. Since the incidence of graft failure is high in myelofibrosis patients, a secondary HSCT using PTCy may be successful if employed. PMID:27853082

Age-Dependent Risk of Graft Failure in Young Kidney Transplant Recipients.

PubMed

Kaboré, Rémi; Couchoud, Cécile; Macher, Marie-Alice; Salomon, Rémi; Ranchin, Bruno; Lahoche, Annie; Roussey-Kesler, Gwenaelle; Garaix, Florentine; Decramer, Stéphane; Pietrement, Christine; Lassalle, Mathilde; Baudouin, Véronique; Cochat, Pierre; Niaudet, Patrick; Joly, Pierre; Leffondré, Karen; Harambat, Jérôme

2017-06-01

The risk of graft failure in young kidney transplant recipients has been found to increase during adolescence and early adulthood. However, this question has not been addressed outside the United States so far. Our objective was to investigate whether the hazard of graft failure also increases during this age period in France irrespective of age at transplantation. Data of all first kidney transplantation performed before 30 years of age between 1993 and 2012 were extracted from the French kidney transplant database. The hazard of graft failure was estimated at each current age using a 2-stage modelling approach that accounted for both age at transplantation and time since transplantation. Hazard ratios comparing the risk of graft failure during adolescence or early adulthood to other periods were estimated from time-dependent Cox models. A total of 5983 renal transplant recipients were included. The risk of graft failure was found to increase around the age of 13 years until the age of 21 years, and decrease thereafter. Results from the Cox model indicated that the hazard of graft failure during the age period 13 to 23 years was almost twice as high as than during the age period 0 to 12 years, and 25% higher than after 23 years. Among first kidney transplant recipients younger than 30 years in France, those currently in adolescence or early adulthood have the highest risk of graft failure.

Goal disturbance changes pre/post-renal transplantation are related to changes in distress.

PubMed

de Vries, Alicia M; Schulz, Torben; Westerhuis, Ralf; Navis, Gerjan J; Niesing, Jan; Ranchor, Adelita V; Schroevers, Maya J

2017-09-01

Renal transplantation (RTx) is considered the treatment of choice for end-stage renal disease (ESRD) given its association with lower mortality, and improved overall quality of life and psychological functioning compared to dialysis. However, much less is known about which factors underlie these psychological improvements across RTx. Goal theory suggests that experienced disturbances in important goals are related to lower psychological functioning. This study aimed to (1) identify the most disturbed and most important goals for patients before RTx, (2) to examine changes in goal disturbance and goal importance pre/post-RTx, and (3) to examine whether changes in goal disturbance are associated with changes in psychological distress over time, and whether this relationship is mediated by changes in perceived control. In this longitudinal study, 220 patients completed questionnaires before and after RTx, including questionnaires to assess goals (GOALS questionnaire), psychological distress (GHQ-12), and perceived control (Mastery scale). End-stage renal disease affected both general and disease-specific goals. Approximately 30% of the patients indicated to experience high or very high disturbance before transplantation. Goal disturbance generally decreased significantly pre- to post-RTx, whereas goal importance did not change significantly pre- to post-RTx. No mediation effect of perceived control was found. Instead, both changes in goal disturbance and perceived control showed independent effects on changes in distress. Intervention strategies targeting attainable and realistic goal setting, and perceived control in RTx recipients who do not benefit optimally from RTx, might enhance psychological functioning in this population. Statement of contribution What is already known on this subject? Kidney transplantation improves patients' psychological functioning. Experienced disturbances in important life goals are related to lower psychological functioning in chronic

Liver transplantation in the Nordic countries – An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982–2013

PubMed Central

Fosby, Bjarte; Melum, Espen; Bjøro, Kristian; Bennet, William; Rasmussen, Allan; Andersen, Ina Marie; Castedal, Maria; Olausson, Michael; Wibeck, Christina; Gotlieb, Mette; Gjertsen, Henrik; Toivonen, Leena; Foss, Stein; Makisalo, Heikki; Nordin, Arno; Sanengen, Truls; Bergquist, Annika; Larsson, Marie E.; Soderdahl, Gunnar; Nowak, Greg; Boberg, Kirsten Muri; Isoniemi, Helena; Keiding, Susanne; Foss, Aksel; Line, Pål-Dag; Friman, Styrbjörn; Schrumpf, Erik; Ericzon, Bo-Göran; Höckerstedt, Krister; Karlsen, Tom H.

2015-01-01

Abstract Aim and background. The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. Materials and methods. The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. Results. Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004–2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. Conclusion. The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR). PMID:25959101

The Oral Cavity State in Renal Transplant Recipients

PubMed Central

Gašpar, Marija; Glavina, Ana; Grubišić, Kristina; Sabol, Ivan; Bušić, Mirela; Mravak, Marinka

2015-01-01

Aim Patients with a solid organ transplant can have many different complications in the mouth, as a result of immunosuppression and side effects of drugs. The aim of this study was to examine the frequency and type of oral lesions in renal transplant patients, dental status, oral hygiene, oral lesions related to drugs which patients take and the time of transplantation as well as the frequency of patient’s visits to the dentist in the post-transplant period. Material and methods The study was performed in a period of two years and included 100 subjects with a renal transplant during their regular control visits to the Department of Nephrology and Dialysis, Clinical Hospital Centre Zagreb and the Department of Oral Medicine, School of Dental Medicine, University of Zagreb and 100 randomly selected control subjects at the Department of Endodontics and Restorative Dentistry, School of Dental Medicine, University of Zagreb. Results Results showed a significantly higher incidence of oral lesions in patients with renal transplant (31%) compared to control subjects. The most frequent were erythematous (inflammatory changes), keratotic lesions and gingival hyperplasia. The average DMFT index was significantly lower in patients with renal transplant than in the control group. One third of patients had a subjective feeling of dry mouth. Oral hygiene was poor overall, and only a small number of subjects used the additional sustainers for oral hygiene. Most patients did not visit the dentist after the transplantation. Conclusion Renal transplant patients need a comprehensive and regular dental care during the pre- and post-transplant period and a doctor of dental medicine should be part of a multidisciplinary team of medical specialists. PMID:27688404

Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment.

PubMed

Peláez-Jaramillo, Maria J; Cárdenas-Mojica, Allison A; Gaete, Paula V; Mendivil, Carlos O

2018-04-01

Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.

Long-Term Survival of Photoreceptors Transplanted into the Adult Murine Neural Retina Requires Immune Modulation

PubMed Central

West, Emma L.; Pearson, Rachael A.; Barker, Susie E.; Luhmann, Ulrich F. O.; Maclaren, Robert E.; Barber, Amanda C.; Duran, Yanai; Smith, Alexander J.; Sowden, Jane C.; Ali, Robin R.

2012-01-01

Stem cell therapy presents an opportunity to replace photoreceptors that are lost as a result of inherited and age-related degenerative disease. We have previously shown that murine postmitotic rod photoreceptor precursor cells, identified by expression of the rod-specific transcription factor Nrl, are able to migrate into and integrate within the adult murine neural retina. However, their long-term survival has yet to be determined. Here, we found that integrated Nrl.gfp+ve photoreceptors were present up to 12 months post-transplantation, albeit in significantly reduced numbers. Surviving cells had rod-like morphology, including inner/outer segments and spherule synapses. In a minority of eyes, we observed an early, marked reduction in integrated photoreceptors within 1 month post-transplantation, which correlated with increased numbers of amoeboid macrophages, indicating acute loss of transplanted cells due to an inflammatory response. In the majority of transplants, similar numbers of integrated cells were observed between 1 and 2 months post-transplantation. By 4 months, however, we observed a significant decrease in integrated cell survival. Macrophages and T cells were present around the transplantation site, indicating a chronic immune response. Immune suppression of recipients significantly increased transplanted photoreceptor survival, indicating that the loss observed in unsuppressed recipients resulted from T cell-mediated host immune responses. Thus, if immune responses are modulated, correctly integrated transplanted photoreceptors can survive for extended periods of time in hosts with partially mismatched H-2 haplotypes. These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective. PMID:20857496

An individualised risk-adapted protocol of pre- and post transplant zoledronic acid reduces bone loss after allogeneic stem cell transplantation: results of a phase II prospective trial.

PubMed

Grigg, A; Butcher, B; Khodr, B; Bajel, A; Hertzberg, M; Patil, S; D'Souza, A B; Ganly, P; Ebeling, P; Wong, E

2017-09-01

Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure. Of 82 patients enrolled, 70 were alive and without relapse at day 100. A single pretransplant dose of ZA prevented femoral neck bone loss at day 100 compared with baseline (mean change -2.6±4.6%). Using the risk-adapted protocol, 42 patients received ZA between days 100 and 365 post alloSCT, and this minimised bone loss at day 365 compared with pretransplant levels (mean change -2.9±5.3%). Femoral neck bone loss was significantly reduced in ZA-treated patients compared with historical untreated controls at days 100 and 365. This study demonstrates that a single dose of ZA pre-alloSCT prevents femoral neck bone loss at day 100 post alloSCT, and that a risk-adapted algorithm is able to guide ZA administration from days 100 to 365 post transplant and minimise further bone loss.

The potential association of CMV-specific CD8+ T lymphocyte reconstitution with the risk of CMV reactivation and persistency in post allogeneic stem cell transplant patients.

PubMed

Shams El-Din, Ahmed Ali; El-Desoukey, Nermeen Ahmed; Amin Tawadrous, Dalia Gamil; Fouad, Neveen Mohammed Baha El-Din; Abdel-Mooti, Mohammed; Hotar, Said Fathy

2018-01-09

development of cytomegalovirus (CMV)-specific CD8+ T cell response is crucial in preventing symptomatic CMV infection specially, in stem cell transplant (SCT) patients. The aim of this study was to evaluate CMV-specific CD8+ T cell reconstitution in allogeneic SCT recipients and to study the possible association between CMV-specific CD8+ T cell recovery with protection from CMV reactivation and persistency. Human leuKocyte antigen (HLA)-tetramers were used for CMV-specific CD8+ cell quantitation by Flow cytometry in twenty post-allogeneic SCT patients. Nine patients (45%) developed rapid recovery of CMV-specific CD8+ cells, among them; 7 patients (78%) had no CMV reactivation in the first 95 days post-transplant. Five patients had developed persistent CMV viremia; all of them had not developed CMV-specific CD8+ recovery till day 95 post-transplant. Patients with persistent CMV viremia had a statistically significant lower means of CMV-specific CD8+ percent and absolute count compared to those without persistent viremia (p = .001, .015), respectively. The incidence of CMV reactivation and persistency was higher among patients with delayed CMV-specific CD8+ reconstitution in the first 95 days post-transplant. CMV-specific CD8+ cells can help in categorizing patients into risk groups: (early recovery/low risk) and (delayed recovery/increased risk), this tool may guide clinicians in the selection of patients who may profit from prophylactic antiviral therapy and frequent viral monitoring.

Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Manbok, E-mail: manbok66@dankook.ac.kr; Rahman, Masmudur M.; Cogle, Christopher R.

Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignanciesmore » in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.« less

Sinusitis in patients undergoing allogeneic bone marrow transplantation - a review.

PubMed

Drozd-Sokolowska, Joanna Ewa; Sokolowski, Jacek; Wiktor-Jedrzejczak, Wieslaw; Niemczyk, Kazimierz

Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31-955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT) prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT), preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Outcomes of Early Adolescent Donor Hearts in Adult Transplant Recipients.

PubMed

Madan, Shivank; Patel, Snehal R; Vlismas, Peter; Saeed, Omar; Murthy, Sandhya; Forest, Stephen; Jakobleff, William; Sims, Daniel; Lamour, Jacqueline M; Hsu, Daphne T; Shin, Julia; Goldstein, Daniel; Jorde, Ulrich P

2017-12-01

This study sought to determine outcomes of adult recipients of early adolescent (EA) (10 to 14 years) donor hearts. Despite a shortage of donor organs, EA donor hearts (not used for pediatric patients) are seldom used for adults because of theoretical concerns for lack of hormonal activation and changes in left ventricular mass. Nonetheless, the outcomes of adult transplantation using EA donor hearts are not clearly established. All adult (≥18 years of age) heart transplant recipients in the United Network for Organ Sharing database between April 1994 and September 2015 were eligible for this analysis. Recipients of EA donor hearts were compared with recipients of donor hearts from the usual adult age group (ages 18 to 55 years). Main outcomes were all-cause mortality and cardiac allograft vasculopathy up to 5 years, and primary graft failure up to 90 days post-transplant. Propensity score analysis was used to identify a cohort of recipients with similar baseline characteristics. Of the 35,054 eligible adult recipients, 1,123 received hearts from EA donors and 33,931 from usual-age adult donors. With the use of propensity score matching, 944 recipients of EA donor hearts were matched to 944 recipients of usual-age adult donor hearts. There was no difference in 30-day, 1-year, 3-year, and 5-year recipient survival or primary graft failure rates in the 2 groups using both Cox hazards ratio and Kaplan-Meier analysis. Of note, adult patients who received EA donor hearts had a trend toward less cardiac allograft vasculopathy (Cox hazard ratio, 0.80; 95% confidence interval: 0.62 to 1.01; p = 0.07). In this largest analysis to date, we found strong evidence that EA donor hearts, not used for pediatric patients, can be safely transplanted in appropriate adult patients and have good outcomes. This finding should help increase the use of EA donor hearts. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Early graft function and carboxyhemoglobin level in liver transplanted patients.

PubMed

Ali, Yasser; Negmi, H; Elmasry, N; Sadek, M; Riaz, A; Al Ouffi, H; Khalaf, H

2007-10-01

Heme-Oxygenase-1 catalyzes hemoglobin into bilirubin, iron, and carbon monoxide, a well known vasodilator. Heme-Oxygenase-1 expression and carbon monoxide production as measured by blood carboxyhemoglobin levels, increase in end stage liver disease patients. We hypothesized that there may be a correlation between carboxyhemoglobin level and early graft function in patients undergoing liver transplant surgeries. In a descriptive retrospective study, 39 patients who underwent liver transplantation between the year 2005 and 2006 at KFSH&RC, are included in the study. All patients received general anesthesia with isoflurane in 50% oxygen and air. Levels of oxyhemoglobin, carboxyhemoglobin and methemoglobin concentration in percentage were recorded at preoperative time, anhepatic phase, end of surgery, ICU admission and 24 hr after surgery. The level of lactic acid, prothrombin time (PT), partial thrombin time (PTT), serum total bilirubin and ammonia were also recorded at ICU admission and 24 hr after surgery. The numbers of blood units transfused were recorded. 39 patients were included in the study with 13/39 for living donor liver transplant (LDLT) compared to 26/39 patients scheduled for deceased donor liver transplant (DDLT). The mean age was 35.9 +/- 16.9 years while the mean body weight was 60.3 +/- 20.9 Kg. Female to male ratio was 21/18. The median packed red blood cell (PRBC) units was 4 (Rang 0-40). There was a significant increase in carboxyhemoglobin level during the anhepatic phase, end of surgery and on ICU admission compared with preoperative value (p<0.005). However, there was insignificant changes in methemoglobin level and significant decrease in oxyhemoglobin levels throughout the study period compared to the preoperative value (p<0.005). The changes in carboxyhemoglobin level on ICU admission and 24 hrs postoperatively were positively correlated with the changes in serum total bilirubin and prothrombin time (R = 0.35, 0.382, 0.325 and 0

Increased duration of dual pegylated interferon and ribavirin therapy for genotype 1 hepatitis C post-liver transplantation increases sustained virologic response: a retrospective review.

PubMed

Wells, Malcolm M; Roth, Lee S; Marotta, Paul; Levstik, Mark; Mason, Andrew L; Bain, Vincent G; Chandok, Natasha; Aljudaibi, Bandar M

2013-01-01

In patients with advanced post-transplant hepatitis C virus (HCV) recurrence, antiviral treatment (AVT) with interferon and ribavirin is indicated to prevent graft failure. The aim of this study was to determine and report Canadian data with respect to the safety, efficacy, and spontaneous virologic response (SVR) predictors of AVT among transplanted patients with HCV recurrence. A retrospective chart review was performed on patients transplanted in London, Ontario and Edmonton, Alberta from 2002 to 2012 who were treated for HCV. Demographic, medical, and treatment information was collected and analyzed. A total of 85 patients with HCV received pegylated interferon with ribavirin post-liver transplantation and 28 of the 65 patients (43%) with genotype 1 achieved SVR. Of the patients having genotype 1 HCV who achieved SVR, there was a significantly lower stage of fibrosis (1.37 ± 0.88 vs. 1.89 ± 0.96; P = 0.03), increased ribavirin dose (total daily dose 1057 ± 230 vs. 856 ± 399 mg; P = 0.02), increased rapid virologic response (RVR) (6/27 vs. 0/31; P = 0.05), increased early virologic response (EVR) (28/28 vs. 18/35; P = 0.006), and longer duration of therapy (54.7 ± 13.4 weeks vs. 40.2 ± 18.7; P = 0.001). A logistic regression model using gender, age, RVR, EVR, anemia, duration of therapy, viral load, years' post-transplant, and type of organ (donation after cardiac death vs. donation after brain death) significantly predicted SVR (P < 0.001), with duration of therapy having a significant odds ratio of 1.078 (P = 0.007). This study identified factors that predict SVR in HCV-positive patients who received dual therapy post-transplantation. Extending therapy from 48 weeks to 72 weeks of dual therapy is associated with increased SVR rates. Future studies examining the role of extended therapy are needed to confirm these findings, since the current study is a retrospective one.

Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.

PubMed

Hoskote, Aparna; Burch, Michael

2015-06-01

Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level >2.5 mg/dL (221 μmol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care.

Continuous monitoring of kidney transplant perfusion with near-infrared spectroscopy.

PubMed

Malakasioti, Georgia; Marks, Stephen D; Watson, Tom; Williams, Fariba; Taylor-Allkins, Mariesa; Mamode, Nizam; Morgan, Justin; Hayes, Wesley N

2018-05-11

Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitoring tissue oxygenation percutaneously. NIRS monitoring of kidney transplant perfusion has not previously been validated to the gold standard of DUS. We examined whether NIRS tissue oxygenation indices can reliably assess blood flow in established paediatric kidney transplants. Paediatric kidney transplant recipients ages 1-18 years with stable allograft function were eligible. Participants underwent routine DUS assessment of kidney transplant perfusion, including resistive index (RI) and peak systolic velocity at the upper and lower poles. NIRS data [tissue oxygenation index (TOI%)] were recorded for a minimum of 2 min with NIRS sensors placed on the skin over upper and lower allograft poles. Twenty-nine subjects with a median age of 13.3 (range 4.8-17.8) years and a median transplant vintage of 26.5 months participated. Thirteen (45%) were female and 20 (69%) were living donor kidney recipients. NIRS monitoring was well tolerated by all, with 96-100% valid measurements. Significant negative correlations were observed between NIRS TOI% and DUS RI at both the upper and lower poles (r = -0.4 and -0.6, P = 0.04 and 0.001, respectively). Systolic blood pressure but not estimated glomerular filtration rate also correlated with NIRS TOI% (P = 0.01). NIRS indices correlate well with DUS perfusion and haemodynamic parameters in established paediatric kidney transplant recipients. Further studies are warranted to extend NIRS use for continuous real-time monitoring of early post-transplant perfusion status.

Acute Kidney Injury after Liver Transplantation.

PubMed

Durand, François; Francoz, Claire; Asrani, Sumeet K; Khemichian, Saro; Pham, Thomas A; Sung, Randall S; Genyk, Yuri S; Nadim, Mitra K

2018-05-29

Since the implementation of the MELD score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of post liver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post LT AKI which then predisposes to posttransplant chronic kidney disease (CKD). Prevention of posttransplant AKI is essential in the improvement of long term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate (GFR). New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post LT in patients with early posttransplant AKI may improve GFR in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late CKD.

The number of lung transplants can be safely doubled using extended criteria donors; a single-center review.

PubMed

Meers, Caroline; Van Raemdonck, Dirk; Verleden, Geert M; Coosemans, Willy; Decaluwe, Herbert; De Leyn, Paul; Nafteux, Philippe; Lerut, Toni

2010-06-01

Relaxing the standard lung donor criteria may significantly increase the reported 15% organ yield but post-transplant recipient outcome should be carefully monitored. Charts from all consecutive deceased organ donors within our hospital network were reviewed over a 2-year period. Reasons for lung refusals and number of lungs transplanted were analysed. Hospital outcome including early recipient survival was compared between standard- and extended criteria donors. Out of 283 referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of these effective donors were declined for lung donation because of chest X-ray abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at our center, 23 from standard criteria donors versus 27 from extended criteria donors. There were no significant differences in hospital outcome and in early survival between lung recipients from both donor groups. Lung acceptance rate (34.1%) in our donor network is 10-20% higher than reported figures. The number of lung transplants in our center doubled by accepting extended criteria donors. This policy did not negatively influence our results after lung transplantation.

No survival benefit to gaining private health insurance coverage for post-lung transplant care in adults with cystic fibrosis.

PubMed

Tumin, Dmitry; Foraker, Randi E; Tobias, Joseph D; Hayes, Don

2016-03-01

The use of public insurance is associated with diminished survival in patients with cystic fibrosis (CF) following lung transplantation. No data exist on benefits of gaining private health insurance for post-transplant care among such patients previously using public insurance. The United Network for Organ Sharing database was used to identify first-time lung transplant recipients participating in Medicare or Medicaid, diagnosed with CF, and transplanted between 2005 and 2015. Survival outcomes were compared between recipients gaining private insurance after transplantation and those maintaining public coverage throughout follow-up. Since implementation of the lung allocation score, 575 adults with CF received lung transplantation funded by Medicare or Medicaid and contributed data on insurance status post-transplant. There were 128 (22%) patients who gained private insurance. Multivariable analysis of time-varying insurance status found no survival benefit of gaining private insurance (HR = 0.822; 95% CI = 0.525, 1.286; p = 0.390). Further analysis demonstrated that resuming public insurance coverage was detrimental, relative to gaining and keeping private insurance (HR = 2.315; 95% CI = 1.020, 5.258; p = 0.045). Survival disadvantages of lung transplant recipients with CF who have public health insurance were not ameliorated by a switch to private coverage for post-transplant care. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ex vivo administration of trimetazidine improves post-transplant lung function in pig model.

PubMed

Cosgun, Tugba; Iskender, Ilker; Yamada, Yoshito; Arni, Stephan; Lipiski, Miriam; van Tilburg, Koen; Weder, Walter; Inci, Ilhan

2017-07-01

Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed. There was a trend towards better oxygenation during EVLP in the TMZ group ( P  = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P  < 0.05). Tissue thiobarbituric acid levels, myeloperoxidase activity and protein concentrations in bronchoalveolar lavage samples were significantly lower in the TMZ group at the end of EVLP ( P  < 0.05). Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

High circulating CD4+CD25hiFOXP3+ T-cell sub-population early after lung transplantation is associated with development of bronchiolitis obliterans syndrome.

PubMed

Durand, Maxim; Lacoste, Philippe; Danger, Richard; Jacquemont, Lola; Brosseau, Carole; Durand, Eugénie; Tilly, Gaelle; Loy, Jennifer; Foureau, Aurore; Royer, Pierre-Joseph; Tissot, Adrien; Roux, Antoine; Reynaud-Gaubert, Martine; Kessler, Romain; Mussot, Sacha; Dromer, Claire; Brugière, Olivier; Mornex, Jean François; Guillemain, Romain; Claustre, Johanna; Degauque, Nicolas; Magnan, Antoine; Brouard, Sophie

2018-06-01

Chronic bronchiolitis obliterans syndrome (BOS) remains a major limitation for long-term survival after lung transplantation. The immune mechanisms involved and predictive biomarkers have yet to be identified. The purpose of this study was to determine whether peripheral blood T-lymphocyte profile could predict BOS in lung transplant recipients. An in-depth profiling of CD4 + and CD8 + T cells was prospectively performed on blood cells from stable (STA) and BOS patients with a longitudinal follow-up. Samples were analyzed at 1 and 6 months after transplantation, at the time of BOS diagnosis, and at an intermediate time-point at 6 to 12 months before BOS diagnosis. Although no significant difference was found for T-cell compartments at BOS diagnosis or several months beforehand, we identified an increase in the CD4 + CD25 hi FoxP3 + T-cell sub-population in BOS patients at 1 and 6 months after transplantation (3.39 ± 0.40% vs 1.67 ± 0.22% in STA, p < 0.001). A CD4 + CD25 hi FoxP3 + T-cell threshold of 2.4% discriminated BOS and stable patients at 1 month post-transplantation. This was validated on a second set of patients at 6 months post-transplantation. Patients with a proportion of CD4 + CD25 hi FoxP3 + T cells up to 2.4% in the 6 months after transplantation had a 2-fold higher risk of developing BOS. This study is the first to report an increased proportion of circulating CD4 + CD25 hi FoxP3 + T cells early post-transplantation in lung recipients who proceed to develop BOS within 3 years, which supports its use as a BOS predictive biomarker. Copyright © 2018. Published by Elsevier Inc.

The role of suture cutout in the failure of meniscal root repair during the early post-operative period: a biomechanical study.

PubMed

Perez-Blanca, Ana; Prado Nóvoa, María; Lombardo Torre, Maximiano; Espejo-Reina, Alejandro; Ezquerro Juanco, Francisco; Espejo-Baena, Alejandro

2018-04-01

To assess the role of suture cutout in the mechanics of failure of the repaired posterior meniscal root during the early post-operative period when using sutures of different shape. Twenty medial porcine menisci were randomized in two groups depending on the suture shape used to repair the posterior root: thread or tape. The sutured menisci were subjected to cyclic loading (1000 cycles, (10, 30) N) followed by load-to-failure testing. Residual displacements, stiffness, and ultimate failure load were determined. During tests, the tissue-suture interface was recorded using a high-resolution camera. In cyclic tests, cutout progression at the suture insertion points was not observed for any specimen of either group and no differences in residual displacements were found between use of thread or tape. In load-to-failure tests, suture cutout started in all menisci at a load close to the ultimate failure and all specimens failed by suture pullout. Suture tape had a greater ultimate load with no other differences. In a porcine model of a repaired posterior meniscal root subjected to cyclic loads representative of current rehabilitation protocols in the early post-operative period under restricted loading conditions, suture cutout was not found as a main source of permanent root displacement when using suture thread or tape. Suture cutout progression started at high loading levels close to the ultimate load of the construct. Tape, with a meniscus-suture contact area larger than thread, produced higher ultimate load.

[Mold infections in lung transplants].

PubMed

Solé, Amparo; Ussetti, Piedad

2014-01-01

Invasive infections by molds, mainly Aspergillus infections, account for more than 10% of infectious complications in lung transplant recipients. These infections have a bimodal presentation: an early one, mainly invading bronchial airways, and a late one, mostly focused on lung or disseminated. The Aspergillus colonization at any time in the post-transplant period is one of the major risk factors. Late colonization, together with chronic rejection, is one of the main causes of late invasive forms. A galactomannan value of 0.5 in bronchoalveolar lavage is currently considered a predictive factor of pulmonary invasive infection. There is no universal strategy in terms of prophylaxis. Targeted prophylaxis and preemptive treatment instead of universal prophylaxis, are gaining more followers. The therapeutic drug monitoring level of azoles is highly recommended in the treatment. Monotherapy with voriconazole is the treatment of choice in invasive aspergillosis; combined antifungal therapies are only recommended in severe, disseminated, and other infections due to non-Aspergillus molds. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

PubMed

Nicoletto, Bruna Bellincanta; Pedrollo, Elis Forcellini; Carpes, Larissa Salomoni; Coloretti, Natália Gomes; Krolikowski, Thaiana Cirino; Souza, Gabriela Corrêa; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti; Canani, Luis Henrique

2018-01-01

The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; p<0.01) and increased at one year (53.15 ± 2.55 ng/mL; p<0.01 vs. three months), remaining significantly lower than before transplantation (p<0.01) (pover time<0.01). At one year after transplantation, there was a significant increase in body mass index, trunk fat and waist circumference compared to immediate period after transplantation. Progranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

Factors contributing to employment patterns after liver transplantation.

PubMed

Beal, Eliza W; Tumin, Dmitry; Mumtaz, Khalid; Nau, Michael; Tobias, Joseph D; Hayes, Don; Washburn, Kenneth; Black, Sylvester M

2017-06-01

Many liver transplant recipients return to work, but their patterns of employment are unclear. We examine patterns of employment 5 years after liver transplantation. First-time liver transplant recipients ages 18-60 years transplanted from 2002 to 2009 and surviving at least 5 years were identified in the United Network for Organ Sharing registry. Recipients' post-transplant employment status was classified as follows: (i) never employed; (ii) returned to work within 2 years and remained employed (continuous employment); (iii) returned to work within 2 years, but was subsequently unemployed (intermittent employment); or (iv) returned to work ≥3 years post-transplant (delayed employment). Of 28 306 liver recipients identified during the study period, 12 998 survived at least 5 years and contributed at least 1 follow-up of employment status. A minority of patients (4654; 36%) were never employed, while 3780 (29%) were continuously employed, 3027 (23%) were intermittently employed, and 1537 (12%) had delayed employment. In multivariable logistic regression analysis, predictors of intermittent and delayed employment included lower socioeconomic status, higher local unemployment rates, and post-transplant comorbidities or complications. Never, intermittent, and delayed employment are common after liver transplantation. Socioeconomic and labor market characteristics may add to clinical factors that limit liver transplant recipients' continuous employment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term outcomes and management of the heart transplant recipient.

PubMed

McCartney, Sharon L; Patel, Chetan; Del Rio, J Mauricio

2017-06-01

Cardiac transplantation remains the gold standard in the treatment of advanced heart failure. With advances in immunosuppression, long-term outcomes continue to improve despite older and higher risk recipients. The median survival of the adult after heart transplantation is currently 10.7 years. While early graft failure and multiorgan system dysfunction are the most important causes of early mortality, malignancy, rejection, infection, and cardiac allograft vasculopathy contribute to late mortality. Chronic renal dysfunction is common after heart transplantation and occurs in up to 68% of patients by year 10, with 6.2% of patients requiring dialysis and 3.7% undergoing renal transplant. Functional outcomes after heart transplantation remain an area for improvement, with only 26% of patients working at 1-year post-transplantation, and are likely related to the high incidence of depression after cardiac transplantation. Areas of future research include understanding and managing primary graft dysfunction and reducing immunosuppression-related complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Post-Transplant Lymphoproliferative Disorder (PTLD) Manifesting in the Oral Cavity of a 13-Year-Old Liver Transplant Recipient (LTx).

PubMed

Krasuska-Sławińska, Ewa; Minko-Chojnowska, Izabela; Pawłowska, Joanna; Dembowska-Bagińska, Bożenna; Pronicki, Maciej; Olczak-Kowalczyk, Dorota

2015-08-18

BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a potential complication of solid organ or bone marrow transplants. The main PTLD risk factors are: the Epstein-Barr virus (EBV), transplant type, and use of immunosuppressants. It mainly consists of an uncontrolled growth of lymphocytes in transplant recipients under chronic immunosuppressive therapy. About 85% of PTLDs are EBV-containing B-cell proliferations; 14% are T-cell proliferations, of which only 40% contain EBV; and the remaining 1% is NK-cell or plasmocyte proliferations. PTLD may present various clinical manifestations, from non-specific mononucleosis-like syndrome to graft or other organ damage resulting from pathologic lymphocyte infiltration. PTLD may manifest in the oral cavity. CASE REPORT The objective of this study was to present the case of a 13-year-old female living-donor liver transplant recipient, resulting from biliary cirrhosis caused by congenital biliary atresia, with exophytic fibrous lesions on buccal mucosa and tongue. Exophytic and hyperplastic lesion of oral mucosa were removed and histopathological examination revealed polymorphic PTLD. The patient underwent 6 cycles of CHOP chemotherapy and all the oral lesions regressed completely. CONCLUSIONS All oral pathological lesions in organ transplant recipients need to be surgically removed and histopathologically examined because they present an increased risk of neoplastic transformations such as PTLD.

Impact of post-kidney transplant parathyroidectomy on allograft function

PubMed Central

Parikh, Samir; Nagaraja, Haikady; Agarwal, Anil; Samavedi, Srinivas; Von Visger, Jon; Nori, Uday; Andreoni, Kenneth; Pesavento, Todd; Singh, Neeraj

2013-01-01

Background The impact of parathyroidectomy on allograft function in kidney transplant patients is unclear. Methods We conducted a retrospective, observational study of all kidney transplant recipients from 1988 to 2008 who underwent parathyroidectomy for uncontrolled hyperparathyroidism (n = 32). Post-parathyroidectomy, changes in estimated glomerular filtration rate (eGFR) and graft loss were recorded. Cross-sectional associations at baseline between eGFR and serum calcium, phosphate, and parathyroid hormone (PTH), and associations between their changes within subjects during the first two months post-parathyroidectomy were assessed. Results Post-parathyroidectomy, the mean eGFR declined from 51.19 mL/min/1.73 m2 at parathyroidectomy to 44.78 mL/min/1.73 m2 at two months (p < 0.0001). Subsequently, graft function improved, and by 12 months, mean eGFR recovered to 49.76 mL/min/1.73 m2 (p = 0.035). Decrease in serum PTH was accompanied by a decrease in eGFR (p = 0.0127) in the first two months post-parathyroidectomy. Patients whose eGFR declined by ≥ 20% (group 1) in the first two months post-parathyroidectomy were distinguished from the patients whose eGFR declined by <20% (group 2). The two groups were similar except that group 1 had a higher baseline mean serum PTH compared with group 2, although not significant (1046.7 ± 1034.2 vs. 476.6 ± 444.9, p = 0.14). In group 1, eGFR declined at an average rate of 32% (p < 0.0001) during the first month post-parathyroidectomy compared with 7% (p = 0.1399) in group 2, and the difference between these two groups was significant (p = 0.0003). The graft function recovered in both groups by one yr. During median follow-up of 66.00 ± 49.45 months, 6 (18%) patients lost their graft with a mean time to graft loss from parathyroidectomy of 37.2 ± 21.6 months. The causes of graft loss were rejection (n = 2), pyelonephritis (n = 1) and chronic allograft nephropathy (n = 3). No graft loss occurred during the first-year post

Improved Survival in Pediatric Heart Transplant Recipients: Have White, Black and Hispanic Children Benefited Equally?

PubMed Central

Singh, T. P.; Almond, C. S.; Gauvreau, K.

2014-01-01

We assessed whether the improvement in post-transplant survival in pediatric heart transplant (HT) recipients during the last 2 decades has benefited the major racial groups in the US equally. We analyzed all children <18 years of age who underwent their first HT in the US during 1987–2008. We compared trends in graft loss (death or re-transplant) in white, black and Hispanic children in 5 successive cohorts (1987–1992, 1993–1996, 1997–2000, 2001–2004, 2005–2008). The primary endpoint was early graft loss within 6 months post-transplant. Longer-term survival was assessed in recipients who survived the first 6 months. The improvement in early post-transplant survival was similar (hazard ratio [HR] for successive eras 0.80, 95% confidence interval [CI] 0.7, 0.9, P=0.24 for black-era interaction, P=0.22 for Hispanic-era interaction) in adjusted analysis. Longer-term survival was worse in black children (HR 2.2, CI 1.9, 2.5) and did not improve in any group with time (HR 1.0 for successive eras, CI 0.9, 1.1, P=0.57; P=0.19 for black-era interaction, P=0.21 for Hispanic-era interaction). Thus, the improvement in early post-HT survival during the last 2 decades has benefited white, black and Hispanic children equally. Disparities in longer-term survival have not narrowed with time; the survival remains worse in black recipients. PMID:21199352

Functional evaluation of patients treated with osteochondral allograft transplantation for post-traumatic ankle arthritis: one year follow-up.

PubMed

Berti, L; Vannini, F; Lullini, G; Caravaggi, P; Leardini, A; Giannini, S

2013-09-01

Severe post-traumatic ankle arthritis poses a reconstructive challenge in active patients. Whereas traditional surgical treatments, i.e. arthrodesis and arthroplasty, provide good pain relief, arthrodesis is associated to functional and psychological limitations, and arthroplasty is prone to failure in the active patient. More recently the use of bipolar fresh osteochondral allografts transplantation has been proposed as a promising alternative to the traditional treatments. Preliminary short- and long-term clinical outcomes for this procedure have been reported, but no functional evaluations have been performed to date. The clinical and functional outcomes of a series of 10 patients who underwent allograft transplantation at a mean follow-up of 14 months are reported. Clinical evaluation was performed with the AOFAS score, functional assessment by state-of-the-art gait analysis. The clinical score significantly improved from a median of 54 (range 12-65) pre-op to 76.5 (range 61-86) post-op (p=0.002). No significant changes were observed for the spatial-temporal parameters, but motion at the hip and knee joints during early stance, and the range of motion of the ankle joint in the frontal plane (control: 13.8°±2.9°; pre-op: 10.4°±3.1°, post-op: 12.9°±4.2°; p=0.02) showed significant improvements. EMG signals revealed a good recovery in activation of the biceps femoris. This study showed that osteochondral allograft transplantation improves gait patterns. Although re-evaluation at longer follow-ups is required, this technique may represent the right choice for patients who want to delay the need for more invasive joint reconstruction procedures. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulatory dendritic cells for promotion of liver transplant operational tolerance: Rationale for a clinical trial and accompanying mechanistic studies.

PubMed

Thomson, Angus W; Humar, Abhinav; Lakkis, Fadi G; Metes, Diana M

2018-05-01

Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8 + memory T cell responses in the early post-transplant period. Based on these observations, and in view of the critical need to reduce patient dependence on non-specific IS agents that predispose to cardiometabolic side effects and renal insufficiency, we will conduct a first-in-human safety and preliminary efficacy study of donor-derived DCreg infusion to achieve early (18 months post-transplant) complete IS withdrawal in low-risk, living donor liver transplant recipients receiving standard-of-care IS (mycophenolate mofetil, tacrolimus and steroids). We will test the hypothesis that, although donor-derived DCreg are short-lived, they will induce robust donor-specific T cell hyporesponsiveness. We will examine immunological mechanisms by sequential analysis of blood and tissue samples, incorporating cutting-edge technologies. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

T cell costimulation blockade promotes transplantation tolerance in combination with sirolimus and post-transplantation cyclophosphamide for haploidentical transplantation in children with severe aplastic anemia.

PubMed

Jaiswal, Sarita Rani; Bhakuni, Prakash; Zaman, Shamsuz; Bansal, Satish; Bharadwaj, Priyanka; Bhargava, Sneh; Chakrabarti, Suparno

2017-08-01

We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0.04). Chronic GVHD (12.5% vs 56%, p=0.02) and CMV reactivation (30% vs 80%, p=0.03) were also reduced in the COSBL group. T and NK cell subset analysis revealed higher CD56 bright CD16 - NK cells in the CONTROL group (p=0.004), but similar CD56 dim CD16 + NK cells in both groups at day+30. Tregs (CD4 + CD25 + CD127 dim/- FoxP3+) were markedly higher in the COSBL group at day+30 (8.4% vs 1.1%) and the trend was maintained through day+90 (p<0.01). The GVHD and Disease-free survival at one year in the COSBL group was 80% vs. 30% in the CONTROL group (p=0.05). Our preliminary findings suggest that COSBL in combination with PTCy and sirolimus might augment transplantation tolerance in children with SAA, probably due to synergistic effect on early recovery of Tregs. Copyright © 2017 Elsevier B.V. All rights reserved.

Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors.

PubMed

Cura, C I; Lattes, R; Nagel, C; Gimenez, M J; Blanes, M; Calabuig, E; Iranzo, A; Barcan, L A; Anders, M; Schijman, A G

2013-12-01

Organ transplantation (TX) is a novel transmission modality of Chagas disease. The results of molecular diagnosis and characterization of Trypanosoma cruzi acute infection in naïve TX recipients transplanted with organs from infected deceased donors are reported. Peripheral blood and cerebrospinal fluid samples from the TX recipients of organs from infected donors were prospectively and sequentially studied for detection of T. cruzi by means of kinetoplastid DNA polymerase chain reaction (kDNA-PCR). In positive blood samples, a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and quantitative real-time PCR (qPCR) to quantify parasitic loads were performed. Minicircle signatures of T. cruzi infecting populations were also analyzed using restriction fragment length polymorphism (RFLP)-PCR. Eight seronegative TX recipients from four infected donors were studied. In five, the infection was detected at 68.4 days post-TX (36-98 days). In one case, it was transmitted to two of three TX recipients. The comparison of the minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. The five cases were infected by DTU TcV. This report reveals the relevance of systematic monitoring of TX recipients using PCR strategies in order to provide an early diagnosis allowing timely anti-trypanosomal treatment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

[The first national program of pediatric lung transplantation: the experience in pediatric intensive care].

PubMed

Frías Pérez, M; Montero Schiemann, C; Ibarra de la Rosa, I; Ulloa Santamaría, E; Muñoz Bonet, J; Velasco Jabalquinto, M; Pérez Navero, J; Lama Martínez, R; Santos Luna, F; Salvatierra Velázquez, A; López Pujol, J

1999-06-01

The aim of this study was to analyze the postoperative progress and medical management in the Pediatric Intensive Care Unit (PICU) of patients that underwent bilateral lung transplant. From April 1997 to June 1998, 10 pediatric lung transplants were performed at the Hospital Reina Sofía (Córdoba, Spain). There were 4 males and 6 females (mean age 11.5 years, range 5 to 15 years). Indications for transplantation were cystic fibrosis (n = 9) and one pulmonary fibrosis secondary to viral infection. Before the transplant, two patients required mechanical ventilation for acute respiratory decompensation and one patient was ventilator-dependent. Immunosuppression consisted of corticosteroids, azathioprine and cyclosporine or tacrolimus. Post-transplantation management included early extubation, when possible, optimal fluid balance to prevent lung edema, low aggressive mechanical ventilation and adequate treatment of complications, such as rejection and infection. There were no peri-operative mortalities. The mean stay in the PICU was 28 days (median: 17 days) and the mean time on mechanical ventilation was 19 days (median: 5.5 days). The most frequent complications were rejection (n = 8), hyperglycemia (n = 6), renal failure (n = 4), arterial hypertension (n = 4) and respiratory infections (n = 3). There were no airway complications. Even if the post-operative period in pediatric lung transplant patients is difficult, the results have been good with an important improvement in the quality of life of these patients has been achieved.

Serum Uric Acid and Renal Transplantation Outcomes: At Least 3-Year Post-transplant Retrospective Multivariate Analysis

PubMed Central

Zhang, Kun; Gao, Baoshan; Wang, Yuantao; Wang, Gang; Wang, Weigang; Zhu, Yaxiang; Yao, Liyu; Gu, Yiming; Chen, Mo; Zhou, Honglan; Fu, Yaowen

2015-01-01

Since the association of serum uric acid and kidney transplant graft outcome remains disputable, we sought to evaluate the predictive value of uric acid level for graft survival/function and the factors could affect uric acid as time varies. A consecutive cohort of five hundred and seventy three recipients transplanted during January 2008 to December 2011 were recruited. Data and laboratory values of our interest were collected at 1, 3, 6, 12, 24 and 36 months post-transplant for analysis. Cox proportional hazard model, and multiple regression equation were built to adjust for the possible confounding variables and meet our goals as appropriate. The current cohort study lasts for 41.86 ± 15.49 months. Uric acid level is proven to be negatively associated with eGFR at different time point after adjustment for age, body mass index and male gender (standardized β ranges from -0.15 to -0.30 with all P<0.001).Males with low eGFR but high level of TG were on CSA, diuretics and RAS inhibitors and experienced at least one episode of acute rejection and diabetic issue were associated with a higher mean uric acid level. Hyperuricemia was significantly an independent predictor of pure graft failure (hazard ratio=4.01, 95% CI: 1.25-12.91, P=0.02) after adjustment. But it was no longer an independent risk factor for graft loss after adjustment. Interestingly, higher triglyceride level can make incidence of graft loss (hazard ratio=1.442, for each unit increase millimoles per liter 95% CI: 1.008-2.061, P=0.045) and death (hazard ratio=1.717, 95% CI: 1.105-2.665, P=0.016) more likely. The results of our study suggest that post-transplant elevated serum uric acid level is an independent predictor of long-term graft survival and graft function. Together with the high TG level impact on poor outcomes, further investigations for therapeutic effect are needed. PMID:26208103

Pathophysiology of Post Transplant Hypertension in Kidney Transplant: Focus on Calcineurin Inhibitors Induced Oxidative Stress and Renal Sodium Retention and Implications with RhoA/Rho Kinase Pathway.

PubMed

Calò, Lorenzo A; Ravarotto, Verdiana; Simioni, Francesca; Naso, Elena; Marchini, Francesco; Bonfante, Luciana; Furian, Lucrezia; Rigotti, Paolo

2017-01-01

Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule. We examined literature data including those coming from our group regarding the role of oxidative stress and sodium retention in CNIs induced hypertension and their involvement in cardiovascular-renal remodeling. Based on the available data, we have provided support to the activation of RhoA/Rho kinase pathway as an important effector in the pathophysiology of CNIs induced post-transplant hypertension via activation of oxidative stress and sodium retention. Clarification of how the biochemical and molecular mechanisms that regulate the processes involved in CNIs induced post transplant hypertension work and interact, would provide further insights not only into the comprehension of the pathophysiology of CNIs induced post transplant hypertension but could also have a positive impact on the clinical ground through the identification of significant targets. Their specific pharmacologic targeting might have multiple beneficial effects on the whole cardiovascular-renal function. The demonstration that in kidney transplanted patients with CNIs induced post-transplanted hypertension, the

Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis.

PubMed

De Oliveira, Nilto C; Julliard, Walker; Osaki, Satoru; Maloney, James D; Cornwell, Richard D; Sonetti, David A; Meyer, Keith C

2016-10-07

Survival for patients with idiopathic pulmonary fibrosis (IPF) and high lung allocation score (LAS) values may be significantly reduced in comparison to those with lower LAS values. To evaluate outcomes for high-risk IPF patients as defined by LAS values ≥46 (N=42) versus recipients with LAS values <46 (N=89). We retrospectively reviewed records of 131 consecutive patients with IPF who received lung transplants at our institution between 1999 and 2013. The mean LAS was significantly higher (59.5, interquartile range 43.9-75.9 vs. 39.3, interquartile range 37.7-44.3; p<0.01) for the high-risk cohort. The higher LAS cohort had significantly lower percent predicted forced vital capacity (FVC) versus recipients with LAS <46 (41.3±14.1% vs. 53.2±16.2%; p<0.01) and required more supplemental oxygen (7±5 vs. 4±2 L/min, p<0.01) prior to transplant versus recipients with LAS <46. Although the incidence of early post-LTX pulmonary complications was increased for the higher LAS group versus recipients with LAS <46, 30-day mortality and actuarial survival did not differ between the two cohorts. Although lung transplantation in patients with IPF and high LAS values is associated with increased risk of early post-transplant complications, long-term post-transplant survival for our high-LAS cohort was equivalent to that for the lower LAS recipients.

Recipient-donor KIR ligand matching prevents CMV reactivation post-haploidentical T cell-replete transplantation.

PubMed

Zhao, Xiang-Yu; Luo, Xue-Yi; Yu, Xing-Xing; Zhao, Xiao-Su; Han, Ting-Ting; Chang, Ying-Jun; Huo, Ming-Rui; Xu, Lan-Ping; Zhang, Xiao-Hui; Liu, Kai-Yan; Li, Dan; Jiang, Zheng-Fan; Huang, Xiao-Jun

2017-06-01

Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation. Donor-recipient KIR ligand matching decreased CMV reactivation [51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012], refractory CMV infection [17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004] and CMV disease [3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024] by day 100 post-transplantation. In addition, the percentage of γ-interferon expression on donor-derived NK cells was significantly higher in the recipients among the recipient-donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft-versus-host or host-versus-graft direction mismatch on days 30 and 100 post-transplantation (P = 0·036 and 0·047, respectively). These findings have suggested that donor-recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell-mediated protection against CMV reactivation. © 2017 John Wiley & Sons Ltd.

Post-operative imaging in liver transplantation: State-of-the-art and future perspectives

PubMed Central

Girometti, Rossano; Como, Giuseppe; Bazzocchi, Massimo; Zuiani, Chiara

2014-01-01

Orthotopic liver transplantation (OLT) represents a major treatment for end-stage chronic liver disease, as well as selected cases of hepatocellular carcinoma and acute liver failure. The ever-increasing development of imaging modalities significantly contributed, over the last decades, to the management of recipients both in the pre-operative and post-operative period, thus impacting on graft and patients survival. When properly used, imaging modalities such as ultrasound, multidetector computed tomography, magnetic resonance imaging (MRI) and procedures of direct cholangiography are capable to provide rapid and reliable recognition and treatment of vascular and biliary complications occurring after OLT. Less defined is the role for imaging in assessing primary graft dysfunction (including rejection) or chronic allograft disease after OLT, e.g., hepatitis C virus (HCV) recurrence. This paper: (1) describes specific characteristic of the above imaging modalities and the rationale for their use in clinical practice; (2) illustrates main imaging findings related to post-OLT complications in adult patients; and (3) reviews future perspectives emerging in the surveillance of recipients with HCV recurrence, with special emphasis on MRI. PMID:24876739

Multiple indications for everolimus after liver transplantation in current clinical practice

PubMed Central

Bilbao, Itxarone; Dopazo, Cristina; Lazaro, Jose; Castells, Lluis; Caralt, Mireia; Sapisochin, Gonzalo; Charco, Ramon

2014-01-01

AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical practice. METHODS: From October 1988 to December 2012, 1023 liver transplantations were performed in 955 patients in our Unit. Seventy-four patients (7.74%) received immunosuppression with everolimus at some time post-transplantation. Demographic characteristics, everolimus indication, time elapsed from transplantation to the introduction of everolimus, doses and levels administered, efficacy, side effects, discontinuation and post-conversion survival were analyzed. RESULTS: Mean age at the time of conversion to everolimus was 57.7 ± 10 years. Indications for conversion were: refractory rejection 31.1%, extended hepatocellular carcinoma in explanted liver 19%, post-transplant hepatocellular carcinoma recurrence 8.1%, de novo tumour 17.6%, renal insufficiency 8.1%, severe neurotoxicity 10.8%, and others 5.4%. Median time from transplantation to introduction of everolimus was 6 mo (range: 0.10-192). Mean follow-up post-conversion was 22 ± 19 mo (range: 0.50-74). The event for which the drug was indicated was resolved in 60.8% of patients, with the best results in cases of refractory rejection, renal insufficiency and neurotoxicity. Results in patients with cancer were similar to those of a historical cohort treated with other immunosuppressants. The main side effects were dyslipidemia and infections. Post-conversion acute rejection occurred in 14.9% of cases. The drug was discontinued in 28.4% of patients. CONCLUSION: Everolimus at low doses in combination with tacrolimus is a safe immunosuppressant with multiple early and late indications post-liver transplantation. PMID:25032101

Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide.

PubMed

Arango, Marcos; Combariza, Juan F

2017-06-01

Noninfection-related fever can occur after peripheral blood stem cell infusion in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. The objective of this study was to analyze the incidence of fever and characterize some clinical features of affected patients. A retrospective case-series study with 40 patients who received haploidentical hematopoietic stem cell transplantation was carried out. Thirty-three patients (82.5%) developed fever; no baseline characteristic was associated with its development. Median time to fever onset was 25.5h (range, 9.5-100h) and median peak temperature was 39.0°C (range, 38.1-40.5°C). Not a single patient developed hemodynamic or respiratory compromise that required admission to the intensive care unit. Fever was not explained by infection in any case. Ninety-one percent of the febrile episodes resolved within 96h of cyclophosphamide administration. No significant difference in overall survival, event-free survival, or graft versus host disease-free/relapse-free survival was found in the group of febrile individuals after peripheral blood stem cell infusion. Fever after peripheral blood stem cell infusion in this clinical setting was common; it usually subsides with cyclophosphamide administration. The development of fever was not associated with an adverse prognosis. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

[Nosocomial infection in patients receiving a solid organ transplant or haematopoietic stem cell transplant].

PubMed

Moreno Camacho, Asunción; Ruiz Camps, Isabel

2014-01-01

Bacterial infections are the most common infections in solid organ transplant recipients. These infections occur mainly in the first month after transplantation and are hospital-acquired. Nosocomial infections cause significant morbidity and are the most common cause of mortality in this early period of transplantation. These infections are caused by multi-drug resistant (MDR) microorganisms, mainly Gram-negative enterobacteria, non-fermentative Gram-negative bacilli, enterococci, and staphylococci. The patients at risk of developing nosocomial bacterial infections are those previously colonized with MDR bacteria while on the transplant waiting list. Intravascular catheters, the urinary tract, the lungs, and surgical wounds are the most frequent sources of infection. Preventive measures are the same as those applied in non-immunocompromised, hospitalized patients except in patients at high risk for developing fungal infection. These patients need antifungal therapy during their hospitalization, and for preventing some bacterial infections in the early transplant period, patients need vaccinations on the waiting list according to the current recommendations. Although morbidity and mortality related to infectious diseases have decreased during the last few years in haematopoietic stem cell transplant recipients, they are still one of the most important complications in this population. Furthermore, as occurs in the general population, the incidence of nosocomial infections has increased during the different phases of transplantation. It is difficult to establish general preventive measures in these patients, as there are many risk factors conditioning these infections. Firstly, they undergo multiple antibiotic treatments and interventions; secondly, there is a wide variability in the degree of neutropenia and immunosuppression among patients, and finally they combine hospital and home stay during the transplant process. However, some simple measures could be

Long-term success of combined kidney-lung transplantation in a patient with cystic fibrosis.

PubMed

Borro, José M; Rama, Pablo; Rey, Teresa; Fernández-Rivera, Constantino

2013-06-01

Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function. Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.

Long-term results of pediatric liver transplantation in a combined pediatric and adult transplant program.

PubMed

Atkison, Paul R; Ross, B Catherine; Williams, Sandy; Howard, John; Sommerauer, John; Quan, Douglas; Wall, William

2002-06-25

from period 3. Among these patients, 1-year survival was 33% (3/9) for period 1, 83% (5/6) for period 2 and 100% (7/7) for period 3. Eighteen of the 22 deaths occurred within 4 months after surgery. Only 3 (3%) of the 116 patients experienced post-transplant lymphoproliferative disease. Steroids were discontinued (usually within 2 years after surgery) for the following proportions of surviving transplant recipients: 17 (89%) of the 19 patients from period 1, 29 (78%) of the 37 patients from period 2 and 21 (55%) of the 38 patients from period 3. Most of the surviving patients had normal growth (82/94 or 87%) and development (73/94 or 78%), and these outcomes were consistent across the 3 periods of study. Survival and long-term outcomes continue to improve for most children who receive liver transplants. These improvements may be due to improved surgical technique, perioperative care and, to a lesser extent, immunosuppressive therapy.

Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas

PubMed Central

Epperla, Narendranath; Fenske, Timothy S; Hari, Parameswaran N; Hamadani, Mehdi

2015-01-01

Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton’s tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT. PMID:26421260

Early donor management increases the retrieval rate of hearts for transplantation in marginal donors.

PubMed

Abuanzeh, Razi; Hashmi, Faisal; Dimarakis, Ioannis; Khasati, Noman; Machaal, Ali; Yonan, Nizar; Venkateswaran, Rajamiyer V

2015-01-01

present in 28.6% (n=4) and 33.5% (n=4) in Groups A and B, respectively (P=0.793). Cardiopulmonary resuscitation was performed on 3 (21.4%) patients in Group A and 2 (16.7%) in Group B (P=0.759). A history of hypertension was present in 7.1% (n=1) of the Group A and 33.3% (n=4) of the Group B donors. In our study, we were able to retrieve more than half of the potential heart donors as a result of early active donor management without impacting on the post-transplant recipient outcome. Early active donor management may assist in increasing the number of heart transplantations, thus warranting further investigation. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Clinical and immunological relevance of antibodies in solid organ transplantation.

PubMed

Mehra, N K; Baranwal, A K

2016-12-01

The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection. Long-term graft survival too is adversely affected by the presence of either pre- or post-transplant DSA. HLA matching status of the recipient - donor pair - is an important factor in the modulation of humoral response following transplantation and in a way affects de novo development of DSA. Data collected over the past decade clearly indicate significantly lower level of DSAs in optimally matched donor-recipient pairs. HLA mismatches especially those on HLA-DR and HLA-C loci have wider implications on post-transplant graft survival. The presence of circulating anti-HLA antibodies leads to endothelial damage in the newly grafted organ through complement dependent or independent pathways. Although detection of C4d deposition in renal biopsies serves as an important indicator of humoral rejection, its absence does not preclude the presence of DSAs and humoral rejection, and hence, it cannot be relied upon in every case. The emergence of epitope-based screening for anti-HLA antibodies on Luminex platform with high degree of sensitivity has revolutionized the screening for anti-HLA antibodies and DSAs. Studies indicate that humoral response to non-HLA antigens might also have a detrimental effect on allograft survival. High titres of such circulating antibodies may even lead to hyperacute rejection. Pre-emptive testing of solid organ recipients, especially kidney transplant recipients for anti

Predictive factors of short term outcome after liver transplantation: A review

PubMed Central

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-01-01

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients

Predictive factors of short term outcome after liver transplantation: A review.

PubMed

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-07-14

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1(th) and the 5(th) day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients

Stented ureterovesical anastomosis in renal transplantation: does it influence the rate of urinary tract infections?

PubMed

Mathe, Zoltan; Treckmann, J W; Heuer, M; Zeiger, A; Sauerland, S; Witzke, O; Paul, A

2010-01-01

Our objective was to evaluate the impact of routine use of double-J stents on the incidence of urinary tract infection after renal transplantation. We conducted a retrospective-comparative single-centre study in 310 consecutive adult deceased donor kidney recipients transplanted from 2002 to 2006. Patients were divided in two groups, with or without urinary stent implantation. To evaluate the predictive factors for UTI, donor and recipients pre- and post-transplantation data were analysed. Early urological complications and renal function within 12 months of transplantation were included as well. A total of 157 patients were enrolled to a stent (ST) and 153 patients to a no-stent (NST) group. The rate of urinary tract infection at three months was similar between the two groups (43.3% ST vs. 40.1% NST, p = 0.65). Of the identified pathogens Enterococcus and Escherichia coli were the most common species. In multivariate analysis neither age nor immunosuppressive agents, BMI or diabetes seemed to have influence on the rate of UTI. When compared to males, females had a significantly higher risk for UTI (54.0% vs. 33.5%). Prophylactic stenting of the ureterovesical anastomosis does not increase the risk of urinary tract infection in the early postoperative period.

Stented ureterovesical anastomosis in renal transplantation: does it influence the rate of urinary tract infections?

PubMed Central

2010-01-01

Objective Our objective was to evaluate the impact of routine use of double-J stents on the incidence of urinary tract infection after renal transplantation. Methods We conducted a retrospective-comparative single-centre study in 310 consecutive adult deceased donor kidney recipients transplanted from 2002 to 2006. Patients were divided in two groups, with or without urinary stent implantation. To evaluate the predictive factors for UTI, donor and recipients pre- and post-transplantation data were analysed. Early urological complications and renal function within 12 months of transplantation were included as well. Results A total of 157 patients were enrolled to a stent (ST) and 153 patients to a no-stent (NST) group. The rate of urinary tract infection at three months was similar between the two groups (43.3% ST vs. 40.1% NST, p = 0.65). Of the identified pathogens Enterococcus and Escherichia coli were the most common species. In multivariate analysis neither age nor immunosuppressive agents, BMI or diabetes seemed to have influence on the rate of UTI. When compared to males, females had a significantly higher risk for UTI (54.0% vs. 33.5%). Conclusion Prophylactic stenting of the ureterovesical anastomosis does not increase the risk of urinary tract infection in the early postoperative period. PMID:20696641

Employment 12 months after kidney transplantation: An in-depth bio-psycho-social analysis of the Swiss Transplant Cohort.

PubMed

Danuser, Brigitta; Simcox, Amira; Studer, Regina; Koller, Michael; Wild, Pascal

2017-01-01

Return to work with or after a chronic disease is a dynamic process influenced by a variety of interactions between personal, work, societal and medical resources or constraints. The aim of this study was to identify predictors for employment 12 months after transplantation in kidney patients, applying a bio-psycho-social model. All kidney patients followed in the Swiss Transplant Cohort between May 2008 and December 2012, aged 18 to 65 were assessed before, 6 and 12 months after transplantation. Of the 689 included patients, 56.2% worked 12 months post- transplantation compared to 58.9% pre-transplantation. Age, education, self-perceived health (6 months post- transplantation), pre- transplantation employment and receiving an organ from a living donor are significant predictors of employment post- transplantation. Moreover, while self-perceived health increased post- transplantation, depression score decreased only among those employed 12 months post- transplantation. Pre- transplantation employment status was the main predictor for post- transplantation employment (OR = 18.6) and was associated with sex, age, education, depression and duration of dialysis. An organ from a living donor (42.1%) was more frequent in younger patients, with higher education, no diabetes and shorter waiting time to surgery. Transplantation did not increase employment in end-stage kidney disease patients but helped maintaining employment. Pre-transplantation employment has been confirmed to be the most important predictor of post-transplantation employment. Furthermore, socio-demographic and individual factors predicted directly and indirectly the post-transplantation employment status. With living donor, an additional predictor linked to social factors and the medical procedure has been identified.

Transplant tourism--a dangerous journey?

PubMed

Polcari, Anthony J; Hugen, Cory M; Farooq, Ahmer V; Holt, David R; Hou, Susan H; Milner, John E

2011-01-01

While the ethical aspects of transplant tourism have received much attention recently, less has been written about the medical safety of this practice. We retrospectively evaluated the outcomes of patients who purchased organs internationally and presented to our center for follow-up care. Baseline demographic characteristics were recorded. Post-operative outcomes including patient survival, graft survival, five-yr graft function, and complications were assessed. Eight patients who purchased international organs for transplant were identified. The country of transplant was China (n = 3), Pakistan (n = 3), India (n = 1), and the Philippines (n = 1). All patients were born in either Asia or the Middle East and traveled to the region of their ethnicity for transplantation. The mean time to presentation was 49 d post-operatively. The overall one- and two-yr patient survival rates were 87% and 75%, respectively. One patient died of miliary tuberculosis and another of Acinetobacter baumanii sepsis. There was one case of newly acquired hepatitis B infection. At last follow-up, all six surviving patients had functioning grafts with a mean creatinine level of 1.26 mg/dL at five yr. Although intermediate-term graft function is acceptable, the early morbidity and mortality among transplant tourists is high. These results suggest that the associated risks may not justify the trip. © 2010 John Wiley & Sons A/S.

A multivariate analysis of pre-, peri-, and post-transplant factors affecting outcome after pediatric liver transplantation.

PubMed

McDiarmid, Sue V; Anand, Ravinder; Martz, Karen; Millis, Michael J; Mazariegos, George

2011-07-01

The purpose of this study was to identify significant, independent factors that predicted 6 month patient and graft survival after pediatric liver transplantation. The Studies of Pediatric Liver Transplantation (SPLIT) is a multicenter database established in 1995, of currently more than 4000 US and Canadian children undergoing liver transplantation. Previous published analyses from this data have examined specific factors influencing outcome. This study analyzes a comprehensive range of factors that may influence outcome from the time of listing through the peri- and postoperative period. A total of 42 pre-, peri- and posttransplant variables evaluated in 2982 pediatric recipients of a first liver transplant registered in SPLIT significant at the univariate level were included in multivariate models. In the final model combining all baseline and posttransplant events, posttransplant complications had the highest relative risk of death or graft loss. Reoperation for any cause increased the risk for both patient and graft loss by 11 fold and reoperation exclusive of specific complications by 4 fold. Vascular thromboses, bowel perforation, septicemia, and retransplantation, each independently increased the risk of patient and graft loss by 3 to 4 fold. The only baseline factor with a similarly high relative risk for patient and graft loss was recipient in the intensive care unit (ICU) intubated at transplant. A significant center effect was also found but did not change the impact of the highly significant factors already identified. We conclude that the most significant factors predicting patient and graft loss at 6 months in children listed for transplant are posttransplant surgical complications.

Limited Sampling Strategy for Estimating Mycophenolic Acid Exposure on Day 7 Post-Transplant for Two Mycophenolate Mofetil Formulations Derived From 20 Chinese Renal Transplant Recipients.

PubMed

Cai, W; Cai, Q; Xiong, N; Qin, Y; Lai, L; Sun, X; Hu, Y

2018-06-01

To assess the pharmacokinetic properties of mycophenolate mofetil (MMF) dispersible tablets and capsules by the enzyme multiplied immunoassay technique (EMIT) in Chinese kidney transplant recipients in the early post-transplantation phase and to develop the equations to predict mycophenolic acid (MPA) area under the 12-hour concentration-time curve (AUC 0-12h ) using a limited sampling strategy (LSS). Forty patients who underwent renal transplantation from brain-dead donors were randomly divided into dispersible tablets (Sai KE Ping; Hangzhou Zhongmei Huadong Pharma) and capsules (Cellcept; Roche Pharma, Why, NSW, Australia) groups, and treated with MMF combined with combination tacrolimus and prednisone as a basic immunosuppressive regimen. Blood samples were collected before treatment (0) and at 0.5,1, 1.5, 2, 4, 6, 8, 10, and 12 hours post-treatment and 7 days after renal transplantation. Plasma MPA concentrations were measured using EMIT. LSS equations were identified using multiple stepwise linear regression analysis. The peak concentration (C max ) in the MMF dispersible tablets (MMFdt) group (7.0 ± 2.8) mg/L was reduced compared with that in the MMF capsules (MMFc) group (10.8 ± 6.2 mg/L; P = .012); time to peak concentration in the MMFdt group was 3.2 ± 2.3 hours, which was nonsignificantly elevated compared with that of the MMFc group (2.2 ± 1.7 hours). Three-point estimation formulas were generated by multiple linear regression for both groups: MPA-AUC MMFdt  = 3.542 + 3.332C 0.5h  + 1.117C 1.5h  + 3.946C 4h (adjusted r 2  = 0.90, P < .001); MPA-AUC MMFc  = 8.149 + 1.442C 2h  + 1.056C 4h  + 7.133C 6h (adjusted r 2  = 0.88, P < .001). Both predicted and measured AUCs showed good consistency. After treatment with MMF dispersible tables or MMF capsules, the C max of MPA for the MMFdt group was significantly lower than that of the MMFc group; there was no significant difference in other pharmacokinetic parameters. Three-time point equations

Initial Report of the Korean Organ Transplant Registry (KOTRY): Heart Transplantation.

PubMed

Lee, Hae Young; Jeon, Eun Seok; Kang, Seok Min; Kim, Jae Joong

2017-11-01

The Korean Organ Transplant Registry (KOTRY), which was the first national transplant registry in Korea, was founded by the Korean Society for Transplantation and the Korean Center for Disease Control in 2014. Here, we present the initial report of the Korean Heart Transplant Registry. A total of 183 heart transplantation (HTPL) patients performed at 4 nationally representative hospitals were collected from April 2014 to December 2015. We analyzed donor and recipient characteristics, treatment patterns, and immediate post-transplantation outcomes. One hundred and eighty-three patients were enrolled. The mean age of the patients was 50.5±13.5 years. The mean age of the male recipients was 4 years greater than that of the female recipients (51.7±13.3 years vs. 47.9±13.7 years, p<0.050). The mean age of donors was more than 12 years younger than that of heart recipients (37.6±10.1 years). Dilated cardiomyopathy was the predominant cause (69%) of heart failure in recipients, followed by ischemic heart diseases (14%) and valvular heart disease (4%). Rejection episodes were most frequent in the 1-6-month period after transplantation (48%), and rarely required intensive treatment. Infection episodes were most frequent <1 month after transplantation (66%) and bacterial and viral infections were equally reported. The 1-year survival rate was 91.6% and most mortality cases occurred during the perioperative period within 1 month after transplantation. With the establishment of the KOTRY in 2014, it is now possible to present nationwide epidemiological data for HTPL in Korea for the first time. The KOTRY is the first national HTPL registry in Korea, and will continue until 2023. Copyright © 2017. The Korean Society of Cardiology

Recovery of nutritional metabolism after liver transplantation.

PubMed

Sugihara, Kohei; Yamanaka-Okumura, Hisami; Teramoto, Arisa; Urano, Eri; Katayama, Takafumi; Morine, Yuji; Imura, Satoru; Utsunomiya, Tohru; Shimada, Mitsuo; Takeda, Eiji

2015-01-01

Perioperative nutritional assessment is critically important to reflect nutritional management because liver transplantation (LTx) often is undertaken in patients with poor nutritional status. The aim of this study was to evaluate nutritional status, including the non-protein respiratory quotient (npRQ), resting energy expenditure (REE), nitrogen balance, and blood biochemical parameters in patients before and after LTx. Fourteen patients undergoing LTx and 10 healthy controls were enrolled in this study. The npRQ and REE were measured using indirect calorimetry before LTx and at 2, 3, and 4 wk after the procedure. Blood biochemistry and nitrogen balance calculated by 24-h urine collection were performed concurrently with indirect calorimetric measurement; the results were compared between the two groups. Before LTx, npRQ was significantly lower and serum non-esterified fatty acid levels were significantly higher in the patients than in the controls. Furthermore, a negative nitrogen balance was observed in the patients. These, however, improved significantly at 4 wk after LTx. REE did not significantly increase compared with the preoperative values in recipients. Blood biochemistry showed gradually increasing levels of serum cholinesterase and albumin. These failed to reach to normal levels by 4 wk post-transplant. The findings revealed that improvement of nutritional metabolism after LTx may require 4 wk. Additional nutritional strategies, therefore, may be needed to minimize catabolic state during the early post-transplant period. Adequate, individualized nutritional guidance before and after LTx should be performed in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

PubMed

Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

2017-03-01

Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hypertension in kidney transplantation is associated with an early renal nerve sprouting

PubMed Central

Rovella, Valentina; Borri, Filippo; Anemona, Lucia; Giannini, Elena; Giacobbi, Erica; Saggini, Andrea; Palmieri, Giampiero; Anselmo, Alessandro; Bove, Pierluigi; Melino, Gerry; Valentina, Guardini; Tesauro, Manfredi; Gabriele, D’Urso; Di Daniele, Nicola

2017-01-01

Abstract Background. Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods. We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls. Results. Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves. Conclusions. Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation. PMID:28498963

Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents.

PubMed

Greenway, Steven C; Butts, Ryan; Naftel, David C; Pruitt, Elizabeth; Kirklin, James K; Larsen, Ingrid; Urschel, Simon; Knecht, Kenneth; Law, Yuk

2016-04-01

Although used routinely, the pleiotropic benefits of statins remain understudied in children after heart transplantation. We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD). This study was a retrospective review of 964 pediatric (ages 5 to 18 years) heart transplant recipients in the multicenter Pediatric Heart Transplant Study registry from 2001 to 2012. Patients were excluded if they were undergoing re-transplantation, survived <1 year post-transplant, or had missing data regarding statin use. The effects of statins beyond the first year were estimated by Kaplan-Meier and Cox regression multivariable analysis for freedom from PTLD, rejection requiring treatment, any severity of CAV, and survival. Statin use was variable among participating centers with only 30% to 35% of patients ≥10 years of age started on a statin at <1 year post-transplant. After the first year post-transplant, statin-treated children (average age at transplant 13.24 ± 3.29 years) had significantly earlier rejection (HR 1.42, 95% CI 1.11 to 1.82, p = 0.006) compared with untreated children (transplanted at 12 ± 3.64 years) after adjusting for conventional risk factors for rejection. Freedom from PTLD, CAV and overall survival up to 5 years post-transplant were not affected by statin use, although the number of events was small. Statin therapy did not confer a survival benefit and was not associated with delayed onset of PTLD or CAV. Early (<1 year post-transplant) statin therapy was associated with increased later frequency of rejection. These findings suggest that a prospective trial evaluating statin therapy in pediatric heart transplant recipients is warranted. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

[Alteration of Microparticle Levels in Early Complications During Hematopoietic Stem Cell Transplantation].

PubMed

Zhou, Li-Li; Han, Yue; Zhu, Qian; Zhao, Shi-Xiang; Wang, Qian; Zhu, Ming-Qing; Dai, Lan; Shen, Wen-Hong; Wu, De-Pei

2015-12-01

To investigate the alteration of microparticles (MP) in the recipients following hematopoietic stem cell transplantation (HSCT) and its significance, and to search the early diagnostic indicators of thrombotic complications after transplantation. According to the occurrence of transplantation-associated complications, 94 allo-HSCT patients were divided into 4 groups: thrombotic group (VOD n = 7, TMA n = 2), acute graft-versus-host disease (aGVHD) group (n = 27), infection group (n = 41) and non-complication group (n = 17). Alterations of serum concentration of tissue factor positive microparticles (TF(+) MP) and endothelial microparticles (EMP) were analyzed by flow cytometry during the process of conditioning treatment and the early stage after transplantation. The relation of these 2 kinds of MP with complications was analysed. (1) The levels of TF(+) MP and EMP of patients undogoing allo-HSCT before conditioning treatment were obviously higher than those in normal controls, and showed some elevation during different times, but there was no significant statistical difference. Although the levels of TF(+) MP and EMP at the end of conditioning treatment were some higher than those before conditioning treatment, but there was no statistical difference between them. (2)The levels of TF(+) MP and EMP in thrombotic group were obviously higher than those in aGVHD group and infection group (P < 0.05). (3)The levels of TF(+) MP and EMP in thrombotic group at different times were significant differences from those in other groups (P < 0.05), and the levels of TF(+) MP and EMP were no significant difference from those in non-complication group. The increase of the TF(+) MP and EMP levels may be associated with occurrence of thrombosis after transplantation, indicating occurrence of the thrombotic complications, like hepatic vein occulusive disease (HVOD). The dynamically monitoring levels of TF(+) MP and EMP contributes to early discovery of thrombotic complications.

Pediatric heart failure and worsening renal function: association with outcomes after heart transplantation.

PubMed

Rajagopal, Satish K; Yarlagadda, Vamsi V; Thiagarajan, Ravi R; Singh, Tajinder P; Givertz, Michael M; Almond, Christopher S D

2012-03-01

Renal function deteriorates in some children awaiting heart transplantation. This study was initiated to assess the effects of worsening renal function (WRF) on post-heart transplantation outcomes and to determine the effect of waiting-list associated WRF on survival after heart transplantation. All children aged <18 years who underwent their first heart transplantation between 1999 and 2009, had reported plasma creatinine concentrations at listing and at transplantation, and were free of renal replacement therapy at listing were identified using the Organ Procurement and Transplant Network database. The independent effects of WRF on in-hospital mortality and post-discharge survival were assessed using logistic regression and log-rank analyses, respectively. Of the 2,216 children included in the analysis, WRF occurred in 334 (15%) awaiting heart transplantation: WRF was mild (stage 1) in 210 (63%), moderate (stage 2) in 40 (12%), and severe (stage 3) in 84 (25%). All WRF stages were independently associated with in-hospital, post-transplant mortality: mild WRF with adjusted odds ratio (AOR) of 2.1 (95% confidence interval [CI], 1.2-3.5); moderate WRF, 2.7 (95% CI, 1.1-6.7); and severe WRF, 3.6 (95% CI, 2.0-6.5). WRF was not associated with death after discharge (hazard ratio, 1.2; 95% CI, 0.9-1.7) at a median follow-up of 2.7 years. WRF occurs in 15% of children awaiting heart transplantation and is associated with early but not late post-transplant mortality. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Social Media Use by Transplant Recipients for Support and Healing.

PubMed

Grumme, Valarie S; Gordon, Shirley C

2016-12-01

Transplant recipients use a diverse support network that now includes transplant-related social media support groups. The purpose of this study is to explore the use of social media sites by transplant recipients as a potential source of support and healing and the usefulness of Internet postings as a source of rich qualitative data. A qualitative descriptive design was used for the study. A total of 126 retrospective postings from 58 participants were analyzed as they existed on this open publically available Web site over a 20-month period from the selected discussion threads. Two major themes emerged from the data: sharing overwhelming gratitude and finding sanctuary. Sharing overwhelming gratitude was expressed in emotional postings about feelings and letters to donor families. Finding sanctuary described the recipients' perception of the online community as a safe and nonjudgmental environment to discuss sensitive issues and feelings. This study adds to what is known about the unique psychological and emotional needs of transplant recipients. Transplant-related support Web sites offer the opportunity to learn what matters most to transplant recipients and identify gaps in care related to calls for nursing.

Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation as Alternative to Matched Sibling or Unrelated Donor Transplantation for Hodgkin Lymphoma: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

PubMed

Martínez, Carmen; Gayoso, Jorge; Canals, Carmen; Finel, Hervé; Peggs, Karl; Dominietto, Alida; Castagna, Luca; Afanasyev, Boris; Robinson, Stephen; Blaise, Didier; Corradini, Paolo; Itälä-Remes, Maija; Bermúdez, Arancha; Forcade, Edouard; Russo, Domenico; Potter, Michael; McQuaker, Grant; Yakoub-Agha, Ibrahim; Scheid, Christof; Bloor, Adrian; Montoto, Silvia; Dreger, Peter; Sureda, Anna

2017-10-20

Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic

Employment 12 months after kidney transplantation: An in-depth bio-psycho-social analysis of the Swiss Transplant Cohort

PubMed Central

Danuser, Brigitta; Simcox, Amira; Koller, Michael; Wild, Pascal

2017-01-01

Background Return to work with or after a chronic disease is a dynamic process influenced by a variety of interactions between personal, work, societal and medical resources or constraints. The aim of this study was to identify predictors for employment 12 months after transplantation in kidney patients, applying a bio-psycho-social model. Methods All kidney patients followed in the Swiss Transplant Cohort between May 2008 and December 2012, aged 18 to 65 were assessed before, 6 and 12 months after transplantation. Results Of the 689 included patients, 56.2% worked 12 months post- transplantation compared to 58.9% pre-transplantation. Age, education, self-perceived health (6 months post- transplantation), pre- transplantation employment and receiving an organ from a living donor are significant predictors of employment post- transplantation. Moreover, while self-perceived health increased post- transplantation, depression score decreased only among those employed 12 months post- transplantation. Pre- transplantation employment status was the main predictor for post- transplantation employment (OR = 18.6) and was associated with sex, age, education, depression and duration of dialysis. An organ from a living donor (42.1%) was more frequent in younger patients, with higher education, no diabetes and shorter waiting time to surgery. Conclusion Transplantation did not increase employment in end-stage kidney disease patients but helped maintaining employment. Pre-transplantation employment has been confirmed to be the most important predictor of post-transplantation employment. Furthermore, socio-demographic and individual factors predicted directly and indirectly the post-transplantation employment status. With living donor, an additional predictor linked to social factors and the medical procedure has been identified. PMID:28448501

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

PubMed

Dubberke, E R; Reske, K A; Olsen, M A; Bommarito, K; Cleveland, A A; Silveira, F P; Schuster, M G; Kauffman, C A; Avery, R K; Pappas, P G; Chiller, T M

2018-04-01

Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Characteristics of the early immune response following transplantation of mouse ES cell derived insulin-producing cell clusters.

PubMed

Boyd, Ashleigh S; Wood, Kathryn J

2010-06-04

The fully differentiated progeny of ES cells (ESC) may eventually be used for cell replacement therapy (CRT). However, elements of the innate immune system may contribute to damage or destruction of these tissues when transplanted. Herein, we assessed the hitherto ill-defined contribution of the early innate immune response in CRT after transplantation of either ESC derived insulin producing cell clusters (IPCCs) or adult pancreatic islets. Ingress of neutrophil or macrophage cells was noted immediately at the site of IPCC transplantation, but this infiltration was attenuated by day three. Gene profiling identified specific inflammatory cytokines and chemokines that were either absent or sharply reduced by three days after IPCC transplantation. Thus, IPCC transplantation provoked less of an early immune response than pancreatic islet transplantation. Our study offers insights into the characteristics of the immune response of an ESC derived tissue in the incipient stages following transplantation and suggests potential strategies to inhibit cell damage to ensure their long-term perpetuation and functionality in CRT.

CHANGES IN SERUM HOMOCYSTEINE LEVEL FOLLOW TWO DIFFERENT TRENDS IN PATIENTS DURING EARLY POST MYOCARDIAL INFARCTION PERIOD

PubMed Central

Valjevac, Amina; Džubur, Alen; Nakaš-Ićindić, Emina; Hadžović-Džuvo, Almira; Zaćiragić, Asija; Lepara, Orhan; Arslanagić, Amila

2009-01-01

The evolution of homocysteine (Hcy) changes after acute myocardial infarction is still not elucidated. Serum Hcy concentration has been shown to increase between acute and convalescent period after myocardial infarction and stroke, Also a decrease in serum Hcy during acute phase was observed, It is still not clear whether the Hcy is a culprit or an innocent bystander in cardiovascular diseases, Addressing the discrepancies in Hcy changes in patients with acute myocardial infarction might give insight in Hcy role in cardiovascular diseases and offer implications both for the clinical interpretation and patients risk stratification, The aim of the study was to evaluate serum Hcy concentration changes during early post myocardial infarction, The study included 55 patients with AMI from the Clinics for Heart Diseases and Rheumatism at University of Sarajevo Clinics Centre, For Hcy analysis blood was collected on day 2 and 5 after the AMI onset, Serum Hcy concentration was determined quantitatively with fluorescent polarisation immunoassay on AxSYM system, Cluster analysis revealed two groups ofAMI patients with different trends of serum Hcy changes, Increase in serum Hcy concentration was observed in 33 (60,0%) patients (AMI 1 group), while in 22 (40,0%) patients a decrease was observed (AMI 2 group), On day 2, patients in AMI 2 group had significantly higher mean Hcy concentration compared to AMI 1 group of patients (15,27±0,96 and 11,59±0,61 μmol/L p<0,05), On day 5, no significant difference in mean Hcy level between AMI 1 and AMI 2 group of patients was observed (14,86±1,1 vs, 12,75±0,74 μmol/L respectively), Significant differences between AMI 1 and AMI 2 patients were observed in VLDLC levels and CK-MB activity on day 2, Patients in AMI 1 group had significant increase in platelets count from day 2 to day 5 (230,1±11,6 vs. 244,2±11,0; p<0,05). Our study of serial Hcy changes in patients with AMI revealed two different patterns of Hcy changes in early post

Carbachol improves the secretion of transplanted submandibular glands during the latent period after microvascular autologous transplantation for severe keratoconjunctivitis sicca.

PubMed

Liu, X-J; Li, M; Su, J-Z; Wang, Z; Xie, Z; Yu, G-Y

2016-10-01

Poor secretion of transplanted submandibular glands (SMGs) during the latent period may cause duct obstruction and affects the surgical outcome. The objective of this study was to investigate the efficacy and systemic side effects of carbachol on transplanted SMG secretion. Twenty-seven patients who underwent SMG transplantation for severe keratoconjunctivitis sicca were treated with subcutaneous injections of 0.2mg/2ml carbachol at 10 days, 1 month, and/or 3 months after surgery. The effect on secretion was evaluated by Schirmer test and technetium 99m ((99m)Tc) scintigraphy. Systemic side effects were evaluated subjectively using a questionnaire. The results showed that the time to onset varied from 4 to 9min and the duration of action from 50 to 110min after carbachol administration. The secretion at each time point after drug administration was significantly higher than the pre-administration value (all P<0.01). (99m)Tc scintigraphy showed a decline in the dynamic time-activity curve in 26 patients, demonstrating a stimulatory effect on the secretion of carbachol. No serious systemic side effects were experienced. In conclusion, the intermittent administration of carbachol could be an effective and safe strategy to promote secretion from transplanted SMGs in the latent period to prevent duct obstruction. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Early renal function recovery and long-term graft survival in kidney transplantation.

PubMed

Wan, Susan S; Cantarovich, Marcelo; Mucsi, Istvan; Baran, Dana; Paraskevas, Steven; Tchervenkov, Jean

2016-05-01

Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3 months post-KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death-censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37-0.85; P = 0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx. © 2016 Steunstichting ESOT.

Neurologic Complications of Transplantation.

PubMed

Dhar, Rajat

2018-02-01

Neurologic disturbances including encephalopathy, seizures, and focal deficits complicate the course 10-30% of patients undergoing organ or stem cell transplantation. While much or this morbidity is multifactorial and often associated with extra-cerebral dysfunction (e.g., graft dysfunction, metabolic derangements), immunosuppressive drugs also contribute significantly. This can either be through direct toxicity (e.g., posterior reversible encephalopathy syndrome from calcineurin inhibitors such as tacrolimus in the acute postoperative period) or by facilitating opportunistic infections in the months after transplantation. Other neurologic syndromes such as akinetic mutism and osmotic demyelination may also occur. While much of this neurologic dysfunction may be reversible if related to metabolic factors or drug toxicity (and the etiology is recognized and reversed), cases of multifocal cerebral infarction, hemorrhage, or infection may have poor outcomes. As transplant patients survive longer, delayed infections (such as progressive multifocal leukoencephalopathy) and post-transplant malignancies are increasingly reported.

Post-Transplant Blood Transfusions and Pediatric Renal Allograft Outcomes

PubMed Central

Verghese, Priya; Gillingham, Kristen; Matas, Arthur; Chinnakotla, Srinath; Chavers, Blanche

2016-01-01

The association of blood transfusions with graft survival after pediatric kidney transplant (KTx) is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% > 12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival; antibody-mediated and acute cellular rejection, and donor-specific antibody (DSA) free survival. Transfusions <1 month post-KTx did not impact death-censored graft survival (DCGS) (p=NS). Patients transfused >12 months post-KTx had significantly lower 12 month estimated glomerular filtration rate (eGFR) (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS. PMID:27712016

Serial detection of Epstein-Barr virus DNA in sera and peripheral blood leukocyte samples of pediatric renal allograft recipients with persistent mononucleosis-like symptoms defines patients at risk to develop post-transplant lymphoproliferative disease.

PubMed

Campe, Hartmut; Jaeger, Gundula; Abou-Ajram, Claudia; Nitschko, Hans; Griebel, Martin; Montoya, Carmen; Klare, Bernd; Koszinowski, Ulrich

2003-02-01

We tested blood samples of 25 pediatric renal transplant recipients for Epstein-Barr virus (EBV) DNA load by quantitative polymerase chain reaction (PCR). Eleven of these transplant recipients showed clinical persistent mononucleosis-like symptoms years after transplantation (Tx). A quantitation of EBV DNA by PCR in peripheral blood lymphocyte (PBL) and serum samples revealed variable EBV DNA titers. The majority of EBV PCR results in samples of the 14 asymptomatic transplant recipients was repeatedly below detection limit. In contrast, patients with mononucleosis-like symptoms showed persistent EBV genome titers over a period of 6 months, ranging from 75 to 18 750 copies/10 000 PBL and from 680 to 335 000 copies/mL serum, respectively. One child suffering from this mononucleosis-like condition developed an EBV-associated Burkitt-like lymphoma 29 months after Tx. Whereas clinical and histological investigations did not indicate a post-transplant lymphoproliferative disorder (PTLD) until tumor detection, EBV titers in PBL and serum had been high for at least 8 months. We propose that pediatric transplant recipients who show both, recurrent mononucleosis-like symptoms and a sustained high EBV genome load, are at increased risk for severe EBV-related post-transplant complications.

Incidence and risk factors for development of new-onset diabetes after kidney transplantation.

PubMed

Bee, Yong Mong; Tan, Hong Chang; Tay, Tunn Lin; Kee, Terence Ys; Goh, Su Yen; Kek, Peng Chin

2011-04-01

New-onset diabetes after transplantation (NODAT) is an increasingly recognised metabolic complication of kidney transplantation that is associated with increased morbidity and mortality. This study aimed to determine the incidence of NODAT and identify risk factors for development of NODAT among kidney allograft recipients in a single centre. We retrospectively reviewed all kidney allograft recipients in our centre between 1998 and 2007. NODAT were determined using criteria as per American Diabetes Association guidelines. Logistic regression analyses were performed to identify predictors of NODAT. Among 388 patients included in the analysis, NODAT was reported in 94 patients (24.2%) after a median follow-up time of 52.1 months. The cumulative incidence of NODAT was 15.8%, 22.8% and 24.5% at 1, 3, and 5 years following transplantation. Seven clinical factors were independent predictors of NODAT: older age, HLA B13 and B15 phenotypes, use of sirolimus, acute rejections, higher pre-transplant and post-transplant (day 1) plasma glucose levels. Patients with NODAT had poorer outcomes in both graft and patient survival. Our study demonstrates a significant risk and burden of NODAT in an Asian transplant population. Risk stratification and aggressive monitoring of blood glucose early post-transplantation is necessary to identify high-risk patients so that appropriate tailoring of immunosuppression and early institution of lifestyle modifications can be implemented.

Prediction of early postoperative infections in pediatric liver transplantation by logistic regression

NASA Astrophysics Data System (ADS)

Uzunova, Yordanka; Prodanova, Krasimira; Spassov, Lubomir

2016-12-01

Orthotopic liver transplantation (OLT) is the only curative treatment for end-stage liver disease. Early diagnosis and treatment of infections after OLT are usually associated with improved outcomes. This study's objective is to identify reliable factors that can predict postoperative infectious morbidity. 27 children were included in the analysis. They underwent liver transplantation in our department. The correlation between two parameters (the level of blood glucose at 5th postoperative day and the duration of the anhepatic phase) and postoperative infections was analyzed, using univariate analysis. In this analysis, an independent predictive factor was derived which adequately identifies patients at risk of infectious complications after a liver transplantation.

Patients Prioritize Waitlist over Post-Transplant Outcomes When Evaluating Kidney Transplant Centers.

PubMed

Husain, S Ali; Brennan, Corey; Michelson, Ariane; Tsapepas, Demetra; Patzer, Rachel E; Schold, Jesse D; Mohan, Sumit

2018-06-26

Factors that patients value when choosing a transplant center have not been well studied. In order to guide the improvement of patient-facing materials, we conducted an anonymous electronic survey of National Kidney Foundation Patient Panel members that assessed relative importance of patient experience, practical considerations, transplant center reputation, center experience, and waitlist when selecting a transplant center. 409 respondents completed the survey, of whom 68% were kidney transplant recipients and 32% had chronic kidney disease or were on dialysis (CKD). Participants had mean age 56±12 years and were predominantly female (61%), white (79%), and had an associate's degree or higher (68%). Participants most often prioritized waitlist when evaluating transplant centers (transplanted 26%, CKD 40%), and waitlist was almost twice as likely as outcomes to be ranked most important (30% vs 17%). Education level and transplant status were significantly associated with center prioritization. Waitlisted respondents most commonly (48%) relied on physicians for information when selecting a center, while a minority cited transplant-specific organizations. In order to improve shared decision-making, materials outlining center-specific waitlist features should be prioritized. Novel patient-oriented metrics for measuring transplant center quality that align with patient priorities must be explored. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Attained Functional Status Moderates Survival Outcomes of Return to Work After Lung Transplantation.

PubMed

Tumin, Dmitry; Kirkby, Stephen E; Tobias, Joseph D; Hayes, Don

2016-06-01

Returning to work is a desirable outcome of lung transplantation that is selective on attained functional status. Survival implications of post-transplant employment are unclear. The United Network for Organ Sharing registry was queried for first-time lung transplants performed from May 2005 to March 2015 in patients ages 18-64. Attainment of normal functional status post-transplant, defined as a 100 % score on the Karnofsky Performance Scale (KPS), was examined as moderating 5-year survival outcomes of work resumption, using Cox proportional hazards models. Supplemental analysis examined attainment of forced expiratory volume in 1 s (FEV1) ≥80 % predicted as moderating survival implications of post-transplant employment. Of 10,066 patients, 1824 (18 %) returned to work, while 9078 contributed follow-up data on functional status. Multivariable analysis demonstrated a protective effect of work resumption among patients who did not attain normal functional status before returning to work (HR = 0.62; 95 % CI = 0.51, 0.76; p < 0.001). This association was attenuated among transplant recipients who reached 100 % KPS while still unemployed (p < 0.001). Similarly, post-transplant survival was favorably associated with 5-year survival among patients who did not attain at least 80 % predicted FEV1 before returning to work (HR = 0.71; 95 % CI = 0.59, 0.86; p < 0.001). Early return to work after lung transplantation may benefit patients experiencing mild functional limitations. Timing the resumption of employment to coincide with attainment of maximal functional status around 1 year post transplant should be considered.

Living donor liver transplantation in India

PubMed Central

2016-01-01

Liver transplantation is currently in its golden period in India. The number of transplants being performed and the steady increase in the new programs that have emerged over the last decade is a testimony to it. The growth was not smooth, especially in the early years. But a multipronged approach in developing infrastructure and the involvement of multidisciplinary teams in the management of transplant patients has had a major positive impact on the outcome and as a result a positive impetus to the growth of this specialty in India. To date, the majority of transplants performed in India are live donor liver transplants. Deceased donation is more sporadic and concentrated in a couple of regions. With phenomenal increase in transplant activity in India, there is huge potential for streamlining data sharing among programs in India and with the rest of the world to ultimately benefit the transplant community. PMID:27115006

Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

PubMed

Smith, Sonali M; Godfrey, James; Ahn, Kwang Woo; DiGilio, Alyssa; Ahmed, Sairah; Agrawal, Vaibhav; Bachanova, Veronika; Bacher, Ulrike; Bashey, Asad; Bolaños-Meade, Javier; Cairo, Mitchell; Chen, Andy; Chhabra, Saurabh; Copelan, Edward; Dahi, Parastoo B; Aljurf, Mahmoud; Farooq, Umar; Ganguly, Siddhartha; Hertzberg, Mark; Holmberg, Leona; Inwards, David; Kanate, Abraham S; Karmali, Reem; Kenkre, Vaishalee P; Kharfan-Dabaja, Mohamed A; Klein, Andreas; Lazarus, Hillard M; Mei, Matthew; Mussetti, Alberto; Nishihori, Taiga; Ramakrishnan Geethakumari, Praveen; Saad, Ayman; Savani, Bipin N; Schouten, Harry C; Shah, Nirav; Urbano-Ispizua, Alvaro; Vij, Ravi; Vose, Julie; Sureda, Anna; Hamadani, Mehdi

2018-06-15

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P < .0001). Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society. © 2018 American Cancer Society.

Prescriptions analysis by clinical pharmacists in the post-operative period: a 4-year prospective study.

PubMed

Charpiat, B; Goutelle, S; Schoeffler, M; Aubrun, F; Viale, J-P; Ducerf, C; Leboucher, G; Allenet, B

2012-09-01

Clinical pharmacists can help prevent medication errors. However, data are scarce on their role in preventing medication prescription errors in the post-operative period, a high-risk period, as at least two prescribers can intervene, the surgeon and the anesthetist. We aimed to describe and quantify clinical pharmacist' intervention (PIs) during validation of drug prescriptions on a computerized physician order entry system in a post-surgical and post-transplantation ward. We illustrate these interventions, focusing on one clearly identified recurrent problem. In a prospective study lasting 4 years, we recorded drug-related problems (DRPs) detected by pharmacists and whether the physician accepted the PI when prescription modification was suggested. Among 7005 orders, 1975 DRPs were detected. The frequency of PIs remained constant throughout the study period, with 921 PIs (47%) accepted, 383 (19%) refused and 671 (34%) not assessable. The most frequent DRP concerned improper administration mode (26%), drug interactions (21%) and overdosage (20%). These resulted in a change in the method of administration (25%), dose adjustment (24%) and drug discontinuation (23%) with 307 drugs being concerned by at least one PI. Paracetamol was involved in 26% of overdosage PIs. Erythromycin as prokinetic agent, presented a recurrent risk of potentially severe drug-drug interactions especially with other QT interval-prolonging drugs. Following an educational seminar targeting this problem, the rate of acceptation of PI concerning this DRP increased. Pharmacists detected many prescription errors that may have clinical implications and could be the basis for educational measures. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

Characteristics of the Early Immune Response Following Transplantation of Mouse ES Cell Derived Insulin-Producing Cell Clusters

PubMed Central

Boyd, Ashleigh S.; Wood, Kathryn J.

2010-01-01

Background The fully differentiated progeny of ES cells (ESC) may eventually be used for cell replacement therapy (CRT). However, elements of the innate immune system may contribute to damage or destruction of these tissues when transplanted. Methodology/Principal Findings Herein, we assessed the hitherto ill-defined contribution of the early innate immune response in CRT after transplantation of either ESC derived insulin producing cell clusters (IPCCs) or adult pancreatic islets. Ingress of neutrophil or macrophage cells was noted immediately at the site of IPCC transplantation, but this infiltration was attenuated by day three. Gene profiling identified specific inflammatory cytokines and chemokines that were either absent or sharply reduced by three days after IPCC transplantation. Thus, IPCC transplantation provoked less of an early immune response than pancreatic islet transplantation. Conclusions/Significance Our study offers insights into the characteristics of the immune response of an ESC derived tissue in the incipient stages following transplantation and suggests potential strategies to inhibit cell damage to ensure their long-term perpetuation and functionality in CRT. PMID:20532031

Association of high post-transplant soluble CD30 serum levels with chronic allograft nephropathy.

PubMed

Grenzi, Patricia C; Campos, Érika F; Tedesco-Silva, Hélio; Felipe, Claudia R; Franco, Marcello F; Soares, Maria Fernanda; Medina-Pestana, José Osmar; Gerbase-Delima, Maria

2013-12-01

The purpose of this study was to evaluate the association of post-transplant soluble CD30 (sCD30) levels, isolated or in combination with of anti-HLA class II antibodies and of serum creatinine levels, with kidney graft loss due to chronic allograft nephropathy (CAN), and type of lesions in graft biopsies for cause. The study comprised 511 first kidney graft recipients, transplanted at a single center, with a graft functioning for at least 2.8 years. A single blood sample was collected from each patient. sCD30 levels were determined by ELISA, and HLA antibodies by Luminex assay. The minimum follow-up after testing was 9.3 years. High sCD30 levels, set at sCD30 ≥ 34.15 ng/mL, the presence of HLA class II antibodies, and serum creatinine ≥ 1.9 mg/dL were independently associated with CAN-graft loss (P values <0.0001, 0.05, <0.0001, respectively), and the combined hazard ratio for CAN-graft loss was 20.2. Analyses of 166 biopsies for cause showed that high sCD30 levels and creatinine were independently associated with interstitial lesions. Post-transplant sCD30 serum levels, especially in conjunction with information regarding HLA class II antibodies and serum creatinine levels, provide valuable information regarding graft outcome and could be useful for the management of kidney transplant recipients. © 2013.

Hepatitis C and liver transplantation.

PubMed

Martini, Silvia

2018-06-01

Hepatitis C virus (HCV)-related liver disease represents the leading indication for liver transplantation (LT) in the USA and Europe and HCV recurrence is universal in recipients who are viremic at LT. Until a few years ago, pegylated-interferon in association with ribavirin was the only therapeutic strategy, usable only in compensated cirrhotic patients, in order to prevent post-LT viral recurrence. The recent advent of direct-acting antiviral agents (DAAs) has dramatically increased the chances of curative treatment for the transplant population and the debate about which should be the best time for treating the infection is still open: whether to pursue HCV eradication 1) before LT, in order to improve liver function, delist some patients and prevent graft infection; or 2) as early as possible after LT, rather than 3) waiting for hepatitis C recurrence before starting treatment. In addition, in the DAA era, the use of HCV-positive donors may represent a potential approach to safely expanding the donor pool. As more HCV patients achieve cure with DAA regimens, the LT trend for HCV in the future would be expected to mimic the trend observed for hepatitis B virus in the past decade and in the United States, during the DAA-period 2014-2015, the rate of LT wait-listing for HCV complicated by decompensated cirrhosis has already decreased by 32%. This review summarizes the published data and emphasizes DAA treatment applicability to patients with decompensated cirrhosis and to liver transplant recipients.

Incidence and Patient Outcomes in Renal Replacement Therapy After Orthotopic Liver Transplant.

PubMed

Ayhan, Asude; Ersoy, Zeynep; Ulas, Aydin; Zeyneloglu, Pinar; Pirat, Arash; Haberal, Mehmet

2017-02-01

Our objective was to evaluate the incidence of renal replacement therapy after orthotopic liver transplant and to evaluate and analyze patient outcomes. We performed a retrospective analysis of 177 consecutive patients at a tertiary care unit who underwent orthotopic liver transplant between January 2010 and June 2016. Patients who were admitted to the intensive care unit after orthotopic liver transplant and who required renal replacement therapy were included. A total of 177 (79 adult, 98 pediatric) orthotopic liver transplants were performed during the study period. Of these, 35 patients (19%) required renal replacement therapy during the early posttransplantation period. After excluding 5 patients with previous chronic renal failure, 30 patients (17%; 20 adult [25% ], 10 pediatric [10% ]) with acute kidney injury required renal replacement therapy. The mean patient age was 31.1 ± 20.0 years, with a mean Model for End-stage Liver Disease score of 16.7 ± 12.3. Of the patients with acute kidney injury who underwent renal replacement therapy, in-hospital mortality was 23.3% (7 of 30 patients), and 40% remained on dialysis. No significant difference was seen in mortality between early versus delayed initiation of renal replacement therapy in patients with stage 3 acute kidney injury (P = .17). Of liver transplant recipients who present with acute kidney injury, 19% require renal replacement therapy, and in-hospital mortality is 20% in the early postoperative period.

Early outcomes of liver transplants in patients receiving organs from hypernatremic donors.

PubMed

Khosravi, Mohammad Bagher; Firoozifar, Mohammad; Ghaffaripour, Sina; Sahmeddini, Mohammad Ali; Eghbal, Mohammad Hossien

2013-12-01

Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival during liver transplants. However, recent studies have found no association between the donor serum sodium and transplant outcome. This study sought to show the negative effect donor hypernatremia has on initial liver allograft function. This is the first study to investigate international normalized ratio and renal factors of patients with normal and those with hypernatremic donor livers. This study was conducted at the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July 2011. Four hundred seven consecutive adult orthotopic liver transplants were performed at the University of Shiraz Medical Center. There were 93 donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group 2). Posttransplant data after 5 days showed that aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and kidney function did not differ between the groups. Hypernatremia is the most important complication after brain death. Previous studies have suggested donor hypernatremia results in a greater incidence of early postoperative graft dysfunction in liver transplant and is considered one of the extended criteria donor. However, in recent years, this hypothesis has been questioned. Our study shows no difference between patients' initial results of liver and kidney functioning with normal and hypernatremic donor livers. This is the first study to investigate international normalized ratio as a fundamental factor in defining early allograft dysfunction and renal factors between patients with normal and hypernatremic donor's livers.

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

PubMed

Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

2017-03-16

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Nutritional issues in heart transplant candidates and recipients.

PubMed

Amarelli, Cristiano; Buonocore, Marianna; Romano, Gianpaolo; Maiello, Ciro; De Santo, Luca Salvatore

2012-01-01

Heart transplant is the golden standard in the management of end-stage heart failure. Recent studies have pointed out the role of nutritional issues in patients evaluated for heart transplant listing. In particular, extremes in body habitus, cachexia and obesity, have been characterized and identified as independent prognostic factors and clinically relevant target for therapeutic interventions. Effects of such conditions exert a prognostic implication well beyond waiting time up to early post transplant setting. Changes in posttransplant clinical conditions and nutritional status have been recently described in their pattern of presentation and implications on weight gain, reversal of preoperative cachexia and early and late morbidity and mortality. New onset diabetes mellitus and metabolic syndrome have been disclosed as relevant clinical conditions in this setting. Implications for tailoring of immunosuppressive therapy and dietary prescription emerged as main stem of long term recipient management. All this issues have been reviewed focusing on the clinical relevance of this growing body of knowledge and emphasizing the role of a multidisciplinary approach for selection and management of heart transplant recipients.

Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: a matched cohort analysis.

PubMed

Manook, Miriam; Koeser, Leonardo; Ahmed, Zubir; Robb, Matthew; Johnson, Rachel; Shaw, Olivia; Kessaris, Nicos; Dorling, Anthony; Mamode, Nizam

2017-02-18

More than 40% of patients awaiting a kidney transplant in the UK are sensitised with human leucocyte antigen (HLA) antibodies. Median time to transplantation for such patients is double that of unsensitised patients at about 74 months. Removing antibody to perform an HLA-incompatible (HLAi) living donor transplantation is perceived to be high risk, although patient survival data are limited. We compared survival of patients opting for an HLAi kidney transplant with that of similarly sensitised patients awaiting a compatible organ. From the UK adult kidney transplant waiting list, we selected crossmatch positive living donor HLAi kidney transplant recipients who received their transplant between Jan 1, 2007, and Dec 31, 2013, and were followed up to Dec 31, 2014 (end of study). These patients were matched in a 1:4 ratio with similarly sensitised patients cases listed for a deceased-donor transplant during that period. Data were censored both at the time of transplantation (listed only), and at the end of the study period (listed or transplant). We used Kaplan-Meier curves to compare patient survival between HLAi and the matched cohort. Of 25 518 patient listings, 213 (1%) underwent HLAi transplantation during the study period. 852 matched controls were identified, of whom 41% (95% CI 32-50) remained without a transplant at 58 months after matching. We noted no difference in survival between patients who were in the HLAi group compared with the listed only group (log rank p=0·446), or listed or transplant group (log rank p=0·984). Survival of sensitised patients undergoing HLAi in the UK is comparable with those on dialysis awaiting a compatible organ, many of whom are unlikely to be have a transplant. Choosing a direct HLAi transplant has no detrimental effect on survival, but offers no survival benefit, by contrast with similar patients studied in a North American multicentre cohort. UK National Health Service Blood & Transplant and Guy's & St Thomas' National

Associations of Pre-transplant Prescription Narcotic Use with Clinical Complications after Kidney Transplantation

PubMed Central

Lentine, Krista L.; Lam, Ngan N.; Xiao, Huiling; Tuttle-Newhall, Janet E.; Axelrod, David; Brennan, Daniel C.; Dharnidharka, Vikas R.; Yuan, Hui; Nazzal, Mustafa; Zheng, Jie; Schnitzler, Mark A.

2015-01-01

Background Associations of narcotic use before kidney transplantation with post-transplant clinical outcomes are not well described. Methods We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1– 1.7, 1.8–5.4, 5.5–23.7, and ≥23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and non-compliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression. Results The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1% vs. 0.2% (p<0.001); cardiac arrest, 4.7% vs. 2.7% (p<0.05); hypotension, 14% vs. 8% (p<0.0001); hypercapnia, 1.6% vs. 0.9% (p<0.05); mental status changes, 5.3% vs. 2.7% (p<0.001); drug abuse/dependence, 7.0% vs. 1.7% (p<0.0001); alcohol abuse, 1.8% vs. 0.6% (p=0.0001); accidents, 0.9% vs. 0.3% (p<0.05); and non-compliance, 3.5% vs. 2.3% (p<0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2-to-4-times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35% to 45% higher risks of cardiac arrest and hypotension. Conclusion Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation. PMID:25832723

The effect of implant macro-thread design on implant stability in the early post-operative period: a randomized, controlled pilot study.

PubMed

McCullough, Jeffrey J; Klokkevold, Perry R

2017-10-01

Available literature suggests there is a transient drop in implant stability from approximately week 0 to week 3-4 as a result of peri-implant bone remodeling as it transitions from a primary, mechanical stability to a secondary, biological stability. Research investigating the influence of macro-thread design on this process is scant. The specific aim of this study was to evaluate the role of macro-thread design on implant stability in the early post-operative healing period using resonance frequency analysis (RFA). Seven patients, each missing at least two posterior teeth in the same arch, were included in the study. Three patients qualified for four implants resulting in a total of 10 matched pairs. All sites were healed (>6 months), non-grafted sites with sufficient bone to place implants. Each site in a matched pair was randomly assigned to receive either a control (Megagen EZ Plus Internal; EZ) or test (Megagen AnyRidge; AR) implant. The test implant incorporates a novel thread design with a wide thread depth and increased thread pitch. RFA was used to determine implant stability quotient (ISQ) values for each implant at the time of placement and weekly for the first 8 weeks. Implants consistently achieved a relatively high insertion torque (30-45 N/cm) and high initial ISQ value (79.8 ± 1.49). Baseline ISQ values for test (AR; 79.55 ± 1.61) and control (EZ; 80.05 ± 1.37) implants were similar. A general pattern of stability from baseline through all eight follow-up evaluations was observed for the test implants. A pattern of decreasing ISQ values was observed for the control implants across the early follow-up evaluations up to week four, where the value plateaued. There was a statistically significant main effect due to implant type (P < 0.01) and a statistically significant interaction between implant type and time (P < 0.01), indicating that the test and control implants performed differently at certain time points. Within the limitations

Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation.

PubMed

Stubendorff, Beatrice; Finke, Stephanie; Walter, Martina; Kniemeyer, Olaf; von Eggeling, Ferdinand; Gruschwitz, Torsten; Steiner, Thomas; Ott, Undine; Wolf, Gunter; Wunderlich, Heiko; Junker, Kerstin

2014-12-01

Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice. Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay. A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity. Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

Effect of sertraline on complications and survival after hematopoietic stem-cell transplantation, a double-blind, placebo-controlled clinical study.

PubMed

Tavakoli-Ardakani, Maria; Kheshti, Raziyeh; Maryam, Mehrpooya

2017-12-01

Previous studies have found a connection between psychiatric problems and post-hematopoietic stem-cell transplantation (HSCT) complications. We sought to evaluate the effect of sertraline on engraftment time, hospitalization period, mortality, and post-transplantation complications in HSCT recipients with depression and/or anxiety. We recruited adults aged 18-60, who were candidates for autologous or allogeneic HSCT with major depression and/or anxiety disorder. They were administered 50 mg of sertraline or placebo daily for the first week, and then 100 mg for the following seven weeks. We documented occurrence and severity of early post-HSCT complications, including infection, mucositis, nausea and vomiting, diarrhea, pain, renal toxicities and liver complications, acute graft-versus-host disease, and veno-occlusive disease, as well as time to engraftment, length of hospitalization and 6-month mortality. Overall, 56 patients participated in the study (sertraline group n = 30, placebo group n = 26). Of the complications, only mortality and readmission up to 6 months post-transplantation were significantly higher in the placebo group compared to sertraline group (P values = 0.040, 0.028, respectively). There were no significant differences for other complications between the groups. Mean engraftment time was significantly lower in the sertraline group (P value = 0.048). This study provides evidence that sertraline positively influences engraftment time, readmission, and mortality after HSCT.

[Transplant Surgeon Meets Nephrologist: Important Nephrological Aspects Before and After Kidney or Liver Transplantation].

PubMed

Vondran, F W R; Wintterle, S; Bräsen, J H; Haller, H; Klempnauer, J; Richter, N; Lehner, F; Schiffer, M

2017-04-01

In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post-transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation. Georg Thieme Verlag KG Stuttgart · New York.

CMV-specific immune reconstitution following allogeneic stem cell transplantation

PubMed Central

Blyth, Emily; Withers, Barbara; Clancy, Leighton; Gottlieb, David

2016-01-01

ABSTRACT Cytomegalovirus (CMV) remains a major contributor to morbidity and mortality following allogeneic haemopoietic stem cell transplant (HSCT) despite widespread use of viraemia monitoring and pre-emptive antiviral therapy. Uncontrolled viral replication occurs primarily in the first 100 d post transplant but this high risk period can extend to many months if immune recovery is delayed. The re-establishment of a functional population of cellular effectors is essential for control of virus replication and depends on recipient and donor serostatus, the stem cell source, degree of HLA matching and post-transplant factors such as CMV antigen exposure, presence of GVHD and ongoing use of immune suppression. A number of immune monitoring assays exist but have not yet become widely accessible for routine clinical use. Vaccination, adoptive transfer of CMV specific T cells and a number of graft engineering processes are being evaluated to enhance of CMV specific immune recovery post HSCT. PMID:27580355

Early graft dysfunction and mortality rate in marginal donor liver transplantation.

PubMed

Sarkut, Pmar; Gülcü, Bariş; Işçimen, Remzi; Kiyici, Murat; Türker, Gürkan; Topal, Naile Bolca; Ozen, Yilmaz; Kaya, Ekrem

2014-01-01

To determine the effect of marginal donor livers on mortality and graft survival in liver transplantation (LT) recipients. Donors with any 1 of following were considered marginal donors: age ≥65 years, sodium level ≥ 165 mmol/L and cold ischemia time ≥ 12 h. Donors were classified according to the donor risk index (DRI) < 1.7 and ≥ 1.7. The transplant recipients' model for end-stage liver disease (MELD) scores were considered low if < 20 and high if ≥ 20. Early graft dysfunction (EGD) and mortality rate were evaluated. During the study period 47 patients underwent cadaveric LT. The mean age of the donors and recipients was 45 years (range: 5-72 years) and 46 years (range: 4-66 years), respectively. In all, there were 15 marginal donors and 18 donors with a DRI > 1.7. In total, 4 LT patients that received livers from marginal donors and 5 that received livers from donors with a DRI ≥ 1.7 had EGD. Among the recipients of marginal livers, 5 died, versus 4 of the recipients of standard livers. There was no significant difference in EGD or mortality rate between the patients that received livers from marginal donors or those with a DRI ≥ 1.7 and patients that received standard donor livers. Marginal and DRI ≥ 1.7 donors negatively affected LT outcomes, but not significantly.

Augmenting the post-transplantation growth and survivorship of juvenile scleractinian corals via nutritional enhancement.

PubMed

Toh, Tai Chong; Ng, Chin Soon Lionel; Peh, Jia Wei Kassler; Toh, Kok Ben; Chou, Loke Ming

2014-01-01

Size-dependent mortality influences the recolonization success of juvenile corals transplanted for reef restoration and assisting juvenile corals attain a refuge size would thus improve post-transplantation survivorship. To explore colony size augmentation strategies, recruits of the scleractinian coral Pocillopora damicornis were fed with live Artemia salina nauplii twice a week for 24 weeks in an ex situ coral nursery. Fed recruits grew significantly faster than unfed ones, with corals in the 3600, 1800, 600 and 0 (control) nauplii/L groups exhibiting volumetric growth rates of 10.65 ± 1.46, 4.69 ± 0.9, 3.64 ± 0.55 and 1.18 ± 0.37 mm3/week, respectively. Corals supplied with the highest density of nauplii increased their ecological volume by more than 74 times their initial size, achieving a mean final volume of 248.38 ± 33.44 mm3. The benefits of feeding were apparent even after transplantation to the reef. The corals in the 3600, 1800, 600 and 0 nauplii/L groups grew to final sizes of 4875 ± 260 mm3, 2036 ± 627 mm3, 1066 ± 70 mm3 and 512 ± 116 mm3, respectively. The fed corals had significantly higher survival rates than the unfed ones after transplantation (63%, 59%, 56% and 38% for the 3600, 1800, 600 and 0 nauplii/L treatments respectively). Additionally, cost-effectiveness analysis revealed that the costs per unit volumetric growth were drastically reduced with increasing feed densities. Corals fed with the highest density of nauplii were the most cost-effective (US$0.02/mm3), and were more than 12 times cheaper than the controls. This study demonstrated that nutrition enhancement can augment coral growth and post-transplantation survival, and is a biologically and economically viable option that can be used to supplement existing coral mariculture procedures and enhance reef restoration outcomes.

[Mineral and bone disorders in renal transplantation].

PubMed

Bacchetta, Justine; Lafage-Proust, Marie-Hélène; Chapurlat, Roland

2013-12-01

The deregulation of bone and mineral metabolism during chronic kidney disease (CKD) is a daily challenge for physicians, its management aiming at decreasing the risk of both fractures and vascular calcifications. Renal transplantation in the context of CKD, with pre-existing renal osteodystrophy as well as nutritional impairment, chronic inflammation, hypogonadism and corticosteroids exposure, represents a major risk factor for bone impairment in the post-transplant period. The aim of this review is therefore to provide an update on the pathophysiology of mineral and bone disorders after renal transplantation. Copyright © 2013 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients.

PubMed

Husain, Shahid; Kwak, Eun Jeong; Obman, Asia; Wagener, Marilyn M; Kusne, Shimon; Stout, Janet E; McCurry, Kenneth R; Singh, Nina

2004-05-01

The clinical utility of Platelia trade mark Aspergillus galactomannan antigen for the early diagnosis of invasive aspergillosis was prospectively assessed in 70 consecutive lung transplant recipients. Sera were collected twice weekly and tested for galactomannan. Invasive aspergillosis was documented in 17.1% (12/70) of the patients. Using the generalized estimating equation model, at the cutoff value of >or= 0.5, the sensitivity of the test was 30%, specificity 93% with positive and negative likelihood ratios of 4.2 and 0.75, respectively. Increasing the cutoff value to >or= 0.66 yielded a sensitivity of 30%, specificity of 95%, and positive and negative likelihood ratios of 5.5 and 0.74. A total of 14 patients had false-positive tests, including nine who had cystic fibrosis or chronic obstructive pulmonary disease. False-positive tests occurred within 3 days of transplantation in 43% (6/14) of the patients, and within 7 days in 64% (9/14). Thus, the test demonstrated excellent specificity, but a low sensitivity for the diagnosis of aspergillosis in this patient population. Patients with cystic fibrosis or chronic obstructive pulmonary disease may transiently have a positive test in the early post-transplant period.

Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation.

PubMed

Fernandes, Juliana Folloni; Bonfim, Carmem; Kerbauy, Fábio Rodrigues; Rodrigues, Morgani; Esteves, Iracema; Silva, Nathalia Halley; Azambuja, Alessandra Prandini; Mantovani, Luiz Fernando; Kutner, José Mauro; Loth, Gisele; Kuwahara, Cilmara Cristina; Bueno, Clarissa; Kondo, Andrea Tiemi; Ribeiro, Andreza Alice Feitosa; Kok, Fernando; Hamerschlak, Nelson

2018-04-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m 2 , cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.

Small Bowel Transplant

PubMed Central

2003-01-01

EXECUTIVE SUMMARY Objective The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of small bowel transplant in the treatment of intestinal failure. Small Bowel Transplantation Intestinal failure is the loss of absorptive capacity of the small intestine that results in an inability to meet the nutrient and fluid requirements of the body via the enteral route. Patients with intestinal failure usually receive nutrients intravenously, a procedure known as parenteral nutrition. However, long-term parenteral nutrition is associated with complications including liver failure and loss of venous access due to recurrent infections. Small bowel transplant is the transplantation of a cadaveric intestinal allograft for the purpose of restoring intestinal function in patients with irreversible intestinal failure. The transplant may involve the small intestine alone (isolated small bowel ISB), the small intestine and the liver (SB-L) when there is irreversible liver failure, or multiple organs including the small bowel (multivisceral MV or cluster). Although living related donor transplant is being investigated at a limited number of centres, cadaveric donors have been used in most small bowel transplants. The actual transplant procedure takes approximately 12-18 hours. After intestinal transplant, the patient is generally placed on prophylactic antibiotic medication and immunosuppressive regimen that, in the majority of cases, would include tacrolimus, corticosteroids and an induction agent. Close monitoring for infection and rejection are essential for early treatment. Medical Advisory Secretariat Review The Medical Advisory Secretariat undertook a review of 35 reports from 9 case series and 1 international registry. Sample size of the individual studies ranged from 9 to 155. As of May 2001, 651 patients had received small bowel transplant procedures worldwide. According to information from the Canadian Organ Replacement

Nutrition therapy: Integral part of liver transplant care.

PubMed

Anastácio, Lucilene Rezende; Davisson Correia, Maria Isabel Toulson

2016-01-28

Managing malnutrition before liver transplantation (LTx) while on the waiting list and, excessive weight gain/metabolic disturbances in post-surgery are still a challenge in LTx care. The aim of this review is to support an interdisciplinary nutrition approach of these patients. Cirrhotic patients are frequently malnourished before LTx and this is associated with a poor prognosis. Although the relation between nutritional status versus survival, successful operation and recovery after LTx is well established, prevalence of malnutrition before the operation is still very high. Emerging research has also demonstrated that sarcopenia pre and post-transplant is highly prevalent, despite the weight gain in the postoperative period. The diagnosis of the nutritional status is the first step to address the adequate nutritional therapy. Nutritional recommendations and therapy to manage the nutritional status of LTx patients are discussed in this review, regarding counseling on adequate diets and findings of the latest research on using certain immunonutrients in these patients (branched chain amino-acids, pre and probiotics). Nutrition associated complications observed after transplantation is also described. They are commonly related to the adverse effects of immunosuppressive drugs, leading to hyperkalemia, hyperglycemia and weight gain. Excessive weight gain and post-transplant metabolic disorders have long been described in post-LTx and should be addressed in order to reduce associated morbidity and mortality.

Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model.

PubMed

Huda, Kamrul A S M; Guo, Lei; Haga, Sanae; Murata, Hiroshi; Ogino, Tetsuya; Fukai, Moto; Yagi, Takahito; Iwagaki, Hiromi; Tanaka, Noriaki; Ozaki, Michitaka

2006-05-01

Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.

The Effect of Local and Landscape-Level Characteristics on the Abundance of Forest Birds in Early-Successional Habitats during the Post-Fledging Season in Western Massachusetts

PubMed Central

Labbe, Michelle A.; King, David I.

2014-01-01

Many species of mature forest-nesting birds (“forest birds”) undergo a pronounced shift in habitat use during the post-fledging period and move from their forest nesting sites into areas of early-successional vegetation. Mortality is high during this period, thus understanding the resource requirements of post-fledging birds has implications for conservation. Efforts to identify predictors of abundance of forest birds in patches of early-successional habitats have so far been equivocal, yet these previous studies have primarily focused on contiguously forested landscapes and the potential for landscape-scale influences in more fragmented and modified landscapes is largely unknown. Landscape composition can have a strong influence on the abundance and productivity of forest birds during the nesting period, and could therefore affect the number of forest birds in the landscape available to colonize early-successional habitats during the post-fledging period. Therefore, the inclusion of landscape characteristics should increase the explanatory power of models of forest bird abundance in early-successional habitat patches during the post-fledging period. We examined forest bird abundance and body condition in relation to landscape and habitat characteristics of 15 early-successional sites during the post-fledging season in Massachusetts. The abundance of forest birds was influenced by within-patch habitat characteristics, however the explanatory power of these models was significantly increased by the inclusion of landscape fragmentation and the abundance of forest birds in adjacent forest during the nesting period for some species and age groups. Our findings show that including factors beyond the patch scale can explain additional variation in the abundance of forest birds in early-successional habitats during the post-fledging period. We conclude that landscape composition should be considered when siting early-successional habitat to maximize its benefit to

The effect of local and landscape-level characteristics on the abundance of forest birds in early-successional habitats during the post-fledging season in western Massachusetts.

PubMed

Labbe, Michelle A; King, David I

2014-01-01

Many species of mature forest-nesting birds ("forest birds") undergo a pronounced shift in habitat use during the post-fledging period and move from their forest nesting sites into areas of early-successional vegetation. Mortality is high during this period, thus understanding the resource requirements of post-fledging birds has implications for conservation. Efforts to identify predictors of abundance of forest birds in patches of early-successional habitats have so far been equivocal, yet these previous studies have primarily focused on contiguously forested landscapes and the potential for landscape-scale influences in more fragmented and modified landscapes is largely unknown. Landscape composition can have a strong influence on the abundance and productivity of forest birds during the nesting period, and could therefore affect the number of forest birds in the landscape available to colonize early-successional habitats during the post-fledging period. Therefore, the inclusion of landscape characteristics should increase the explanatory power of models of forest bird abundance in early-successional habitat patches during the post-fledging period. We examined forest bird abundance and body condition in relation to landscape and habitat characteristics of 15 early-successional sites during the post-fledging season in Massachusetts. The abundance of forest birds was influenced by within-patch habitat characteristics, however the explanatory power of these models was significantly increased by the inclusion of landscape fragmentation and the abundance of forest birds in adjacent forest during the nesting period for some species and age groups. Our findings show that including factors beyond the patch scale can explain additional variation in the abundance of forest birds in early-successional habitats during the post-fledging period. We conclude that landscape composition should be considered when siting early-successional habitat to maximize its benefit to forest

Risk factors for post-transplant lymphoproliferative disorder after Thymoglobulin-conditioned hematopoietic cell transplantation.

PubMed

Kalra, Amit; Roessner, Cameron; Jupp, Jennifer; Williamson, Tyler; Tellier, Raymond; Chaudhry, Ahsan; Khan, Faisal; Taparia, Minakshi; Jimenez-Zepeda, Victor H; Stewart, Douglas A; Daly, Andrew; Storek, Jan

2018-01-01

Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) occurs frequently when rabbit antithymocyte globulin (ATG) is used in hematopoietic cell transplant (HCT) conditioning. We retrospectively studied 554 patients undergoing ATG-conditioned myeloablative HCT. Strategies used to minimize mortality due to PTLD were either therapy of biopsy-diagnosed PTLD in the absence of EBV DNAemia monitoring (n = 266) or prompt therapy of presumed PTLD (based on clinical/radiologic signs and high EBV DNAemia, in the setting of weekly EBV DNAemia monitoring) (n = 199). Both strategies resulted in similar mortality due to PTLD (0.7% vs 1% at 2 years, P = .43) and similar overall survival (63% vs 67% at 2 years, P = .23) even though there was a trend toward higher PTLD incidence with the prompt therapy. Donor positive with recipient negative EBV (D+R-) serostatus was a risk factor for developing PTLD. Older patient age, HLA-mismatched donor, and graft-versus-host disease were not associated with increased risk of PTLD. In summary, in ATG-conditioned HCT, D+R- serostatus, but not older age, mismatched donor or GVHD is a risk factor for developing PTLD. EBV DNAemia monitoring may be a weak risk factor for developing/diagnosing PTLD; the monitoring coupled with prompt therapy does not improve survival. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ex vivo T-cell-depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy.

PubMed

Anandi, Prathima; Tian, Xin; Ito, Sawa; Muranski, Pawel; Chokshi, Puja D; Watters, Noelle; Chawla, Upneet; Hensel, Nancy; Stroncek, David F; Battiwalla, Minoo; Barrett, A John

2017-06-01

T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10 4 /kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10 7 /kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT. Two hundred seventeen consecutive patients (age range, 10-75 years) with hematologic malignancy (excluding chronic leukemias) underwent ex vivo TCD SCT from HLA-identical sibling donors from 1994-2015. Ninety-four patients had standard-risk disease (first remission acute leukemia [AL] and early stage myelodysplastic syndromes [MDS]) and 123 had high-risk disease (AL beyond first complete remission, advanced MDS or refractory B-cell malignancy). Median follow-up was 8.5 years. At 20 years post-SCT, overall survival (OS) was 40%, nonrelapse mortality (NRM) was 27% and relapse incidence was 39%. Factors affecting outcome in multivariate analysis were transplantation era, with OS increasing from 38% in the period 1994-2000 to 58% in 2011-2015, disease risk (hazard ratio [HR], 1.68 for high risk) and increasing age (HR, 1.19 per decade). Neither the T-cell dose or the add back of T cells in the first 100 days had any effect on OS, NRM and relapse. Outcomes for TCD SCT have greatly improved. However, our data do not support the need to precisely manipulate transplant CD3+ T-cell dose provided at least 3-log depletion is achieved or the use of T-cell add-back. Future improvements for TCD SCT await better strategies to prevent relapse, especially in high-risk recipients. Published by Elsevier Inc.

Lung transplantation in patients with pulmonary emphysema.

PubMed

Paik, Hyo Chae; Hwang, Jung Joo; Lee, Doo Yun

2004-12-31

Lung transplantation is a viable option for patients with chronic obstructive pulmonary disease (COPD), and emphysema is the most common indication to undergo lung transplantation. A total of seven lung and one heart-lung transplantations were performed between July 1996 and June 2004 at the Yongdong Severance Hospital, and herein, three emphysema patients who underwent single lung transplantations are reviewed. There were 2 males and 1 female, with a mean age of 50 years (35, 57 and 58 years). They all underwent an operation, without cardiopulmonary bypass, and there was no operative mortality. The mean survival was 12 months (4 months, 15 months and 17 months) and all succumbed to death due to activation of pulmonary tuberculosis, post-transplantation lymphoproliferative disease and cytomegalovirus (CMV) gastritis associated with asphyxia. Infection was the most common postoperative complication, resulting in longer hospital stays, higher medical expenses and shorter survival rates, necessitating aggressive prophylactic management. The accumulation of experience, modifications to operative procedures and perioperative care may lead to improved early and long-term survival in patients with emphysema undergoing single or bilateral lung transplantations.

Pancreatic Anastomosis Leak 15 Years after Simultaneous Pancreas-Kidney Transplantation from Late-Onset Allograft Cytomegalovirus Duodenal Ulcers Presenting with Gross Hematuria

PubMed Central

Tantisattamo, Ekamol; Chung, Heath; Okado, Manami

2013-01-01

Cytomegalovirus (CMV) infection is one of the most important causes of morbidity and mortality in solid organ transplantation. It can present with hematuria, the most common urological complication in the early post-simultaneous pancreas-kidney (SPK) transplant period. In SPK transplantation, CMV infection usually occurs 1 month after transplantation. We report an instance of bladder-drained SPK transplant presenting with recurrent gross hematuria from CMV infected duodenal graft ulcers 15 years after preserved well-functioning grafts. Serum quantitative Polymerase Chain Reaction (qPCR) for CMV was negative. Postmortem duodenal graft staining for CMV was positive, and revealed the cause of the inciting ulcer. To our knowledge, our patient is the first reported case of very late onset invasive CMV disease causing duodenal graft ulcers 15 years after transplantation, as previously reported cases of posttransplant CMV disease occurred only as late as 18 months. In addition, the absence of correlation between CMV viremia and CMV-infected duodenal allograft in SPK transplant has not been reported. Our case demonstrates that CMV viral load is -unreliable to diagnose invasive CMV disease, and tissue biopsy should be obtained to avoid missed diagnosis causing high morbidity and mortality. PMID:24349888

POST-REPERFUSION LIVER BIOPSY AND ITS VALUE IN PREDICTING MORTALITY AND GRAFT DYSFUNCTION AFTER LIVER TRANSPLANTATION.

PubMed

Zanchet, Marcos Vinícius; Silva, Larissa Luvison Gomes da; Matias, Jorge Eduardo Fouto; Coelho, Júlio Cezar Uili

2016-01-01

The outcome of the patients after liver transplant is complex and to characterize the risk for complications is not always easy. In this context, the hepatic post-reperfusion biopsy is capable of portraying alterations of prognostic importance. To compare the results of liver transplantation, correlating the different histologic features of the hepatic post-reperfusion biopsy with graft dysfunction, primary non-function and patient survival in the first year after transplantation. From the 377 transplants performed from 1996 to 2008, 164 patients were selected. Medical records were reviewed and the following clinical outcomes were registered: mortality in 1, 3, 6 and 12 months, graft dysfunction in varied degrees and primary graft non-function. The post-reperfusion biopsies had been examined by a blinded pathologist for the outcomes. The following histological variables had been evaluated: ischemic alterations, congestion, steatosis, neutrophilic exudate, monomorphonuclear infiltrate and necrosis. The variables associated with increased mortality were: steatosis (p=0.02209), monomorphonuclear infiltrate (p=0.03935) and necrosis (p<0.00001). The neutrophilic exudate reduced mortality in this study (p=0.00659). The primary non-function showed significant association (p<0.05) with the necrosis, steatosis and the monomorphonuclear infiltrate. Post-reperfusion biopsy is useful tool to foresee complications after liver transplant. A evolução dos pacientes após transplante hepático é complexa e caracterizar o risco para complicações nem sempre é fácil. Nesse contexto, a biópsia hepática pós-reperfusão é capaz de retratar alterações de importância prognóstica. Avaliar os resultados no primeiro ano após transplante hepático, correlacionando as alterações histológicas à biópsia hepática pós-reperfusão com a sobrevida, a disfunção e o não-funcionamento primário do enxerto. Dos 377 transplantes ocorridos de 1996 a 2008, 164 pacientes foram

Managing central venous obstruction in cystic fibrosis recipients--lung transplant considerations.

PubMed

Otani, Shinji; Westall, Glen P; Levvey, Bronwyn J; Marasco, Silvana; Lyon, Stuart; Snell, Gregory I

2015-03-01

The superior vena cava (SVC) syndrome in cystic fibrosis (CF) patients is rare, but presents unique challenges in the peri-transplant period. We reviewed our experience of SVC syndrome in CF recipients undergoing lung transplantation. This is a retrospective case series from a single center chart-review. SVC obstruction is defined by clinically significant stenosis or obstruction of the SVC as detected by contrast studies. We identified SVC obstruction in seven post-transplant cases and one pre-transplant case. All eight patients had previous or current history of indwelling central venous catheters. Three recipients experienced operative complications. Five of the seven recipients suffered at least one episode of post-operative SVC obstruction or bleeding despite prophylactic anticoagulation. At a median follow-up of 29 months, six of the seven patients transplanted are well. Strategies are available to minimize the risks of intra/peri-operative acute life-threatening SVC obstruction in CF patients. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

A case of rhabdomyolysis after kidney transplantation successfully managed with intensive continuous dialysis.

PubMed

Shahbazov, Rauf; Fox, Michael; Alejo, Jennifer L; Anjum, Malik A; Azari, Feredun; Doyle, Alden; Agarwal, Avinash; Brayman, Kenneth L

2018-04-01

Rhabdomyolysis is characterized by muscle cell death which can result in acute kidney injury from pigment nephropathy. We present a patient who developed rhabdomyolysis immediately after deceased donor kidney transplantation surgery and was managed with continuous renal replacement therapy that resulted in successful salvage of the kidney allograft. Patients who develop acute kidney failure requiring renal replacement therapy generally have a poor prognosis. It is worth noting that while continuous veno-venous hemofiltration (CVVHF) offers greater volume support and continuous clearance compared to hemodialysis (HD), recent studies have demonstrated no clinically significant improvement in clinical outcome between the two. Perhaps CVVHF is a better modality compared to HD in this setting to prevent further insult from pigment nephropathy to an allograft. A combination of early diagnosis and intensive continuous renal replacement therapy can be used for allograft salvage in a patient with rhabdomyolysis in the immediate post-kidney transplant period.

Outcomes for kidney transplants at the National University Health System: comparison with overseas transplants.

PubMed

Vathsala, Anantharaman

2010-01-01

The 5-year and 10-year graft survivals for 186 deceased donor (DD) transplants performed at National University Health System (NUHS) were 79.9% and 58.4% respectively. 5-year and 10-year patient survivals for DD transplants performed at NUHS were 94.2% and 83.4%. The 5-year and 10-year graft survivals for 128 living donor (LD) transplants performed at NUHS were 90.2% and 72% respectively. 5-year and 10-year patient survivals for DD transplants performed at NUHS were 98.6% and 95.1%. The projected graft half lives were 14.6 and 20.6 years for DD and LD transplants respectively. These results compare favorably with the 10-year survival rates of 40% and 58% for DD and LD grafts reported by the United States Renal Data System (USRDS) in 2010. The younger age and the lower prevalence of diabetes and HLAmismatch in the DD and LD transplant study populations, in comparison to the USRDS population and perhaps better access and compliance to maintenance immunosuppression, could have contributed to these excellent outcomes. The 5-year and 10-year graft survivals for 162 transplants receiving what were likely deceased donor kidneys from China were 89.2% and 69.2% respectively. Although these survivals were apparently better than that for DD performed at NUHS, the advantage for China Tx disappeared when DD with primary non function or vascular thrombosis were excluded from analysis. The 5-year and 10-year patient survivals for 30 transplants receiving live non-related transplants from India were 82.3% and 60.1%. Both groups were considered to have received commercial transplants based on various aspects of history from the patients. Among those receiving China_Tx or India Tx, there were a disproportionate number of males and Chinese; and a significant proportion underwent pre-emptive transplant or transplant after only a short period of dialysis. Prevalence of post-transplant hepatitis B was significantly higher among China_Tx than their DD counterparts (7.7% vs. 1.2%, P = 0

GI complications after lung transplantation in patients with cystic fibrosis.

PubMed

Gilljam, Marita; Chaparro, Cecilia; Tullis, Elizabeth; Chan, Charles; Keshavjee, Shaf; Hutcheon, Michael

2003-01-01

Lung transplantation is now available for patients with cystic fibrosis (CF) and end-stage lung disease. While pulmonary graft function is often considered the major priority following transplantation, the nonpulmonary complications of this systemic disease also continue. We examined the GI complications in a cohort of patients who underwent transplantation. This was a retrospective study of all patients with CF who underwent transplantation between March 1988 and December 1998 in Toronto. Medical records were reviewed, and a short questionnaire was mailed to patients who were alive as of December 1998. There were 80 bilateral lung transplants performed in 75 patients. The questionnaire was distributed to 43 patients, of whom 27 patients (63%) responded. Pancreatic insufficiency requiring enzyme intake was evident in 72 of 75 patients (96%) at the time of surgery. Of three pancreatic-sufficient patients (4%), pancreatic insufficiency was diagnosed in two patients later. Biliary cirrhosis was diagnosed in three patients prior to transplantation. Distal intestinal obstruction syndrome (DIOS) was recorded for 15 patients (20%). Ten patients had a single episode, of which eight episodes occurred early in the postoperative period. Five patients had recurrent episodes. All were medically treated, except for two patients who underwent surgery. Other complications included cholecystitis (n = 3), mucocele of the appendix (n = 1), peptic ulcer disease (n = 3), and colonic carcinoma (n = 1). GI complications after lung transplantation are common in patients with CF, and attention should be paid to the risk for DIOS in the early postoperative period. Prevention and early medical treatment are important in order to avoid acute surgery. Close collaboration with the CF clinic, in order to diagnose and treat CF-related complications, is recommended.

Before the Transplant

MedlinePlus

... effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back ... certain window of time. Be ready for medical tests and possibly a long wait for ... 6: Care Your medical team manages your post-transplant care. They will help you understand the ...

Atrial arrhythmias after lung transplant: underlying mechanisms, risk factors, and prognosis.

PubMed

Orrego, Carlos M; Cordero-Reyes, Andrea M; Estep, Jerry D; Seethamraju, Harish; Scheinin, Scott; Loebe, Matthias; Torre-Amione, Guillermo

2014-07-01

Atrial arrhythmias (AAs) early after lung transplant are frequent and have a significant impact on morbidity and mortality. However, the pathogenesis of AAs after lung transplant remains incompletely understood. In this study we aimed to determine the prevalence of atrial fibrillation (AF) and other AAs, as well as risk factors, clinical outcomes and possible underlying mechanisms associated with AAs after lung transplant. A retrospective analysis was performed on 382 patients who underwent lung transplantation from 2000 to 2010. A 12-lead electrocardiogram (ECG) was obtained and AAs classified as AF and other AAs (atrial flutter [AFL] and supraventricular tachycardia [SVT]). Multivariate logistic regression analysis was performed to determine predictors, and Kaplan-Meier survival curves were constructed. The incidence of AAs was 25%; 17.8% developed AF and 7.6% other AAs (AFL/SVT). The major indication for transplant was idiopathic pulmonary fibrosis (IPF, 35%). Significant predictors of AF were as follows: age; IPF; left atrial enlargement; diastolic dysfunction; and history of coronary artery disease (CAD). Risk factors for other AAs (AFL/SVT) were: age; right ventricle dysfunction; right ventricular enlargement; and elevated right atrial pressure (RAP). One-year mortality was higher in the arrhythmia group (21.5% arrhythmia vs 15.7% no-arrhythmia group; p < 0.05). In addition, patients treated with anti-arrhythmic medications had higher mortality (p < 0.05). AAs are common after lung transplantation. Risk factors for developing either AF or other AAs (AFL/SVT) are different. The development of early AAs post-transplant is associated with prolonged post-operative stay and increased mortality. A rate-control strategy should be used as first-line therapy and anti-arrhythmic agents reserved for those patients who do not respond to the initial treatment. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights

Blood disorders typically associated with renal transplantation

PubMed Central

Yang, Yu; Yu, Bo; Chen, Yun

2015-01-01

Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival. PMID:25853131

Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder.

PubMed

Kalra, Amit; Roessner, Cameron; Jupp, Jennifer; Williamson, Tyler; Tellier, Raymond; Chaudhry, Ahsan; Khan, Faisal; Taparia, Minakshi; Jimenez-Zepeda, Victor H; Stewart, Douglas A; Daly, Andrew; Storek, Jan

2018-05-01

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation (HCT). Epstein-Barr virus (EBV) reactivation (detectable DNAemia) predisposes to the development of PTLD. We retrospectively studied 306 patients monitored for EBV DNAemia after Thymoglobulin-conditioned HCT to determine the utility of the monitoring in the management of PTLD. DNAemia was monitored weekly for ≥12 weeks post-transplantation. Reactivation was detected in 82% of patients. PTLD occurred in 14% of the total patients (17% of patients with reactivation). PTLD was treated with rituximab only when and if the diagnosis was established. This allowed us to evaluate potential DNAemia thresholds for pre-emptive therapy. We suggest 100,000-500,000 IU per mL whole blood as this would result in unnecessary rituximab administration to only 4-20% of patients and near zero mortality due to PTLD. After starting rituximab (for diagnosed PTLD), sustained regression of PTLD occurred in 25/25 (100%) patients in whom DNAemia became undetectable. PTLD progressed or relapsed in 12/17 (71%) patients in whom DNAemia was persistently detectable. In conclusion, for pre-emptive therapy of PTLD, we suggest threshold DNAemia of 100,000-500,000 IU/mL. Persistently detectable DNAemia after PTLD treatment with rituximab appears to have 71% positive predictive value and 100% negative predictive value for PTLD progression/relapse. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation.

PubMed

Yacoub, M H; Banner, N R; Khaghani, A; Fitzgerald, M; Madden, B; Tsang, V; Radley-Smith, R; Hodson, M

1990-01-01

Between September 1984 and October 1988, 27 patients underwent combined heart-lung transplantation for treatment of end-stage respiratory disease caused by cystic fibrosis. The actuarial patient survival was 78% at 1 year and 72% at 2 years. Bacterial respiratory infections were common in the early postoperative period and necessitated vigorous medical therapy. The dose of cyclosporine required in these patients was higher than in conventional transplant recipients, and this contributed to an increased cost of postoperative care. Lung function was greatly improved after transplantation, and long-term survivors achieved an excellent quality of life. Lymphoproliferative disorders developed in two patients; these disorders regressed after a reduction in immunosuppression. Two patients required retransplantation: one because of obliterative bronchiolitis and the other because of recurrent respiratory infections associated with a moderate tracheal stenosis and severe deterioration in lung function. A modification of the technique used for heart-lung transplantation allowed 20 hearts from cystic fibrosis patients to be used for subsequent heart transplantation. Immediate heart function was satisfactory in all cases. The actuarial survival of the recipients of these domino heart transplants was 75% at 1 year. No coronary artery disease was present in the 12 patients who have undergone coronary angiography at 1 year.

Post-transplantation nephroptosis causing recurrent episodes of acute renal failure and hypertension secondary to intermittent vascular torsion of intraperitoneal renal allograft

PubMed Central

Dosch, Austin R.; Pahl, Madeleine; Reddy, Uttam; Foster, Clarence E.

2017-01-01

Abstract Nephroptosis is a rare complication in renal transplantation, but one with significant associated risk. Due to non-specific clinical features, there may be a substantial delay in diagnosis and loss of the transplanted kidney due to renal pedicle thrombosis. We present a case of post-transplantation nephroptosis after simultaneous pancreas and kidney transplant, which resulted in accelerated hypertension and reversible acute kidney injury >1 year after transplantation. Prompt detection of this rare entity leading to expeditious surgical intervention is necessary to preserve viability of the renal allograft. PMID:28560019

Outcome of heart transplants 15 to 20 years ago: graft survival, post-transplant morbidity, and risk factors for mortality.

PubMed

Roussel, Jean C; Baron, Olivier; Périgaud, Christian; Bizouarn, Philippe; Pattier, Sabine; Habash, Oussama; Mugniot, Antoine; Petit, Thierry; Michaud, Jean L; Heymann, Marie Françoise; Treilhaud, Michèle; Trochu, Jean N; Gueffet, Jean P; Lamirault, Guillaume; Duveau, Daniel; Despins, Philippe

2008-05-01

The study was conducted to determine the long-term outcome of patients who underwent heart transplantation 15 to 20 years ago, in the cyclosporine era, and identify risk factors for death. A retrospective analysis was done of 148 patients who had undergone heart transplantation between 1985 and 1991 at a single center. Operative technique and immunosuppressive treatment were comparable in all patients. Actuarial survival rates were 75% (n = 111), 58% (n = 86), and 42% (n = 62) at 5, 10, and 15 years, respectively. The mean follow-up period was 12.1 +/- 5.6 years for patients who survived more than 3 months after transplantation (n = 131). The major causes of death were malignancy (35.8%) and cardiac allograft vasculopathy (24.7%). No death related to acute rejection was reported after the first month of transplantation. Graft coronary artery disease was detected on angiography in 66 (50.3%), and 7 (5.3%) had retransplantation. Malignancies developed in 131 patients (48.1%), including skin cancers in 31 (23.6%), solid tumors in 26 (19.8%), and hematologic malignancies in 14 (10.6%). Severe renal function requiring dialysis or renal transplantation developed in 27 patients (20.6%). By multivariable analysis, the only pre-transplant risk factor found to affect long-term survival was a history of cigarette use (p < 0.0004). Long-term survival at 15 years after cardiac transplantation remains excellent in the cyclosporine era. Controlling acute allograft rejection can be achieved but seems to carry a high rate of cancers and renal dysfunction. History of cigarette use affects significantly long-term survival in our study.

Fifteen-Year Trends in Pediatric Liver Transplants: Split, Whole Deceased, and Living Donor Grafts.

PubMed

Mogul, Douglas B; Luo, Xun; Bowring, Mary G; Chow, Eric K; Massie, Allan B; Schwarz, Kathleen B; Cameron, Andrew M; Bridges, John F P; Segev, Dorry L

2018-05-01

To evaluate changes in patient and graft survival for pediatric liver transplant recipients since 2002, and to determine if these outcomes vary by graft type (whole liver transplant, split liver transplant [SLT], and living donor liver transplant [LDLT]). We evaluated patient and graft survival among pediatric liver-only transplant recipients the PELD/MELD system was implemented using the Scientific Registry of Transplant Recipients. From 2002-2009 to 2010-2015, survival for SLT at 30 days improved (94% vs 98%; P < .001), and at 1 year improved for SLT (89% to 95%; P <.001) and LDLT (93% to 98%; P = .002). There was no change in survival for whole liver transplant at either 30 days (98% in both; P = .7) or 1 year (94% vs 95%; P = .2). The risk of early death with SLT was 2.14-fold higher in 2002-2009 (adjusted hazard ratio [aHR] vs whole liver transplant, 1.47 2.14 3.12 ), but this risk disappeared in 2010-2015 (aHR, 0.65 1.13 1.96 ), representing a significant improvement (P = .04). Risk of late death after SLT was similar in both time periods (aHR 2002-2009, 0.87 1.14 1.48 ; aHR 2010-2015, 0.56 0.88 1.37 ). LDLT had similar risk of early death (aHR 2002-2009, 0.49 1.03 2.14 ; aHR 2010-2015, 0.26 0.74 2.10 ) and late death (aHR 2002-2009, 0.52 0.83 1.32 ; aHR 2010-2015, 0.17 0.44 1.11 ). Graft loss was similar for SLT (aHR, 0.93 1.09 1.28 ) and was actually lower for LDLT (aHR, 0.53 0.71 0.95 ). In recent years, outcomes after the use of technical variant grafts are comparable with whole grafts, and may be superior for LDLT. Greater use of technical variant grafts might provide an opportunity to increase organ supply without compromising post-transplant outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Spontaneous Graft Intra- and Perihepatic Hematoma after Liver Transplantation.

PubMed

Lupaşcu, Cristian; Apopei, Oana; Vlad, Nutu; Vasiluta, Ciprian; Trofin, Ana-Maria; Zabara, Mihai; Vornicu, Alexandra; Lupaşcu-Ursulescu, Corina; Nitu, Mioara; Crumpei, Felicia; Braşoveanu, Vladislav; Popescu, Irinel

2017-01-01

Hematoma of the graft is a life threatening complication of liver transplantation (LT) and there has been no overt conclusion in the literature about optimal management except in scarcely reported cases. It may be either intrahepatic or subcapsular, then again it may develop spontaneously or following parenchimal injuries or transhepatic percutaneous invasive manoeuvers. In this report we describe a rare case of large spontaneous graft intra- and perihepatic hematoma. A 62 year-old man underwent a whole graft orthotopic liver transplantation (OLT) for decompensated chronic liver disease due to alcoholic cirrhosis. The surgical procedure was uneventful. During the early postoperative course, routine Doppler ultrasound examination and CT-scan revealed an extrahepatic paracaval hematoma, 7 days after transplantation, which was stable and conservatively managed until the 18-th postoperative day, when rapidly expanding intraparenchimal hematoma involving the right hemiliver, several other perihepatic hematomas, significant right pleural effusion and hemorrhagic ascites were described. The patient was successfully treated conservatively (nonsurgically) with slow recovery of the liver allograft and discharged one month later in good general status. Celsius.

Use of marginal grafts in deceased donor liver transplant: assessment of early outcomes.

PubMed

Godara, Rajesh; Naidu, C Sudeep; Rao, Pankaj P; Sharma, Sanjay; Banerjee, Jayant K; Saha, Anupam; Vijay, Kapileshwer

2014-03-01

Orthotopic liver transplantation has become a routinely applied therapy for an expanding group of patients with end-stage liver disease. Shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. There is current debate about the regulation and results of liver transplantation using marginal grafts. The study included data of all patients who received deceased donor liver grafts between March 2007 to December 2011. Patients with acute liver failure, living donor transplantation, split liver transplantation, and retransplantation were excluded. Early allograft dysfunction, primary nonfunction, patient survival, and incidence of surgical complications were measured. A total of 33 patients were enrolled in this study. There were 20 marginal and 13 nonmarginal grafts. The two groups were well matched regarding age, sex and indication of liver transplantation, model for end-stage liver disease score, technique of transplant, requirement of vascular reconstruction, warm ischemia time, blood loss, mean operative time, etc. In our study, posttransplant peak level of liver enzymes, international normalization ratio, and bilirubin were not statistically significant in the marginal and nonmarginal group. Wound infection occurred in 10 % of marginal compared with 7.7 % of nonmarginal graft recipients (p > 0.05). In the marginal group, the incidences of vascular complications, hepatic artery thrombosis (four), and portal vein thrombosis (one) were not statistically significant compared to the nonmarginal group. Acute rejection was observed in a total of seven patients (21.2 %)-five (25 %) in the marginal group and two (15.4 %) in the nonmarginal graft recipients. Primary nonfunction occurred in three (9.1 %) patients-two (10 %) in the marginal and one (7.7 %) in the nonmarginal group. Average patient survival for the whole group was 91 % at 1 week, 87.8 % at 3 months, and 84.8 % at 6 months. Because organ scarcity persists, additional

Hypocalcaemia following total thyroidectomy: early post-operative parathyroid hormone assay as a risk stratification and management tool.

PubMed

Islam, S; Al Maqbali, T; Howe, D; Campbell, J

2014-03-01

To develop a practical, efficient and predictive algorithm to manage potential or actual post-operative hypocalcaemia after complete thyroidectomy, using a single post-operative parathyroid hormone assay. This paper reports a prospective study of 59 patients who underwent total or completion thyroidectomy over a period of 24 months. Parathyroid hormone levels were checked post-operatively on the day of surgery, and all patients were evaluated for hypocalcaemia both clinically and biochemically with serial corrected calcium measurements. No patient with an early post-operative parathyroid hormone level of 23 ng/l or more (i.e. approximately twice the lower limit of the normal range) developed hypocalcaemia. All the patients who initially had post-operative hypocalcaemia but had an early parathyroid hormone level of 8 ng/l or more (i.e. approximately two-thirds of the lower limit of the normal range) had complete resolution of their hypocalcaemia within three months. Early post-operative parathyroid hormone measurement can reliably predict patients at risk of post-thyroidectomy hypocalcaemia, and predict those patients expected to recover from temporary hypocalcaemia. A suggested post-operative management algorithm is presented.

Donor Indocyanine Green Clearance Test Predicts Graft Quality and Early Graft Prognosis After Liver Transplantation.

PubMed

Tang, Yunhua; Han, Ming; Chen, Maogen; Wang, Xiaoping; Ji, Fei; Zhao, Qiang; Zhang, Zhiheng; Ju, Weiqiang; Wang, Dongping; Guo, Zhiyong; He, Xiaoshun

2017-11-01

Transplantation centers have given much attention to donor availability. However, no reliable quantitative methods have been employed to accurately assess graft quality before transplantation. Here, we report that the indocyanine green (ICG) clearance test is a valuable index for liver grafts. We performed the ICG clearance test on 90 brain-dead donors within 6 h before organ procurement between March 2015 and November 2016. We also analyzed the relationship between graft liver function and early graft survival after liver transplantation (LT). Our results suggest that the ICG retention rate at 15 min (ICGR15) of donors before procurement was independently associated with 3-month graft survival after LT. The best donor ICGR15 cutoff value was 11.0%/min, and we observed a significant increase in 3-month graft failure among patients with a donor ICGR15 above this value. On the other hand, a donor ICGR15 value of ≤ 11.0%/min could be used as an early assessment index of graft quality because it provides additional information to the transplant surgeon or organ procurement organization members who must maintain or improve organ function to adapt the LT. An ICG clearance test before liver procurement might be an effective quantitative method to predict graft availability and improve early graft prognosis after LT.

Screening retinal transplants with Fourier-domain OCT

NASA Astrophysics Data System (ADS)

Rao, Bin

2009-02-01

Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.

Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients.

PubMed

Kim, Hyun O; Oh, Hyun Jin; Lee, Jae Wook; Jang, Pil-Sang; Chung, Nack-Gyun; Cho, Bin; Kim, Hack-Ki

2013-01-01

Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT). Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's post-transplant immune reconstitution, and therefore require investigation. The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK) cell recovery. The impact of pre- and post-transplant variables, including diagnosis of Epstein-Barr virus (EBV) DNAemia posttransplant, on lymphocyte recovery was evaluated. THE LYMPHOCYTE SUBSETS RECOVERED IN THE FOLLOWING ORDER: NK cells, cytotoxic T cells, B cells, and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16(+)/56(+) cell recovery. Younger patients showed delayed recovery of both CD3(+)/CD8(+) and CD19(+) cells. EBV DNAemia had a deleterious impact on the recovery of both CD3(+) and CD3(+)/CD4(+) lymphocytes at 1 year post-transplant. In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

European Transplant Registry of Senior Renal Transplant Recipients on Advagraf

ClinicalTrials.gov

2016-08-11

Graft Failure; Death; Acute Rejection of Renal Transplant; Infections; Bone Disease; Post Transplant Diabetes Mellitus; Quality of Life; HLA Antibody Production; Cardiovascular Risk Factors; Non-HLA Antibody Production

Surgical anatomy of segmental liver transplantation.

PubMed

Deshpande, R R; Heaton, N D; Rela, M

2002-09-01

The emergence of split and living donor liver transplantation has necessitated re-evaluation of liver anatomy in greater depth and from a different perspective than before. Early attempts at split liver transplantation were met with significant numbers of vascular and biliary complications. Technical innovations in this field have evolved largely by recognizing anatomical anomalies and variations at operation, and devising novel ways of dealing with them. This has led to increasing acceptance of these procedures and decreased morbidity and mortality rates, similar to those observed with whole liver transplantation. The following review is based on clinical experience of more than 180 split and living related liver transplantations in adults and children, performed over a 7-year period from 1994 to 2001. A comprehensive understanding and application of surgical anatomy of the liver is essential to improve and maintain the excellent results of segmental liver transplantation.

Food availability as a determinant of weight gain among renal transplant recipients.

PubMed

Bloodworth, Robin F; Ward, Kenneth D; Relyea, George E; Cashion, Ann K

2014-06-01

Excessive weight gain is common after renal transplantation, but it is unknown whether environmental factors, such as food availability, contribute to this important clinical problem. We evaluated the effects of food availability (fast food restaurants, convenience stores, and grocery stores within 1, 2, and 3 mile buffers of transplant recipients' residences) on body mass index (BMI) change during the first year post-transplant. Participants (n = 299) resided in Memphis, Tennessee. BMI increased by 1.42 units (p < .001) corresponding to an average weight gain of 9.25 lbs (5.43%) during the first year post-transplant. The number of grocery stores within 1 mile of recipient's residence was associated with an increase in BMI (p < .05), but fast food restaurants and convenience stores were not significantly associated with BMI change. © 2014 Wiley Periodicals, Inc.

[Hospitals and other philanthropic foundations in early Byzantine period].

PubMed

Yildirim, R Vedat; Ataç, Adnan

Early Byzantine Period includes between A.D. 330 when Constantinople was established and A.D. 518 when Justinus I became emperor. In this time period, a lot of philanthropic foundations such as hospitals, hospices, orphanages, rest homes and soup kitchens are established. Many of patriarchs and religious men opened them. In some of them, it refers to there was patients' care. The oldest hospital in Constantinople was established by Hasios Marcianos, and was next to Saint Irene Church. In addition to this Empress Flacilla wife of Theodosius the Great made hospitals restored and visited patients regularly. Hospitals were not limited in the center of Empire. Hospitals and other philanthropic foundations were established in Antiochia, Alexandria, Nikea, Adrianopolis, Castoria and Jerusalem. The concept of the modern hospital (the actual care, 'hospitality' and treatment of visitors) for the civilian masses in Europe didn't come to fruition until post Constantine and the rise of Christianity. While these early Christian hospitals were grossly over their heads regarding medical capability (they essentially served as last stops for the dying or quarantine centers), the concept of providing care to the public was the actual intent. In this regard, the first civilian hospitals were developed.

Prospective Epstein-Barr virus-related post-transplant lymphoproliferative disorder prevention program in pediatric allogeneic hematopoietic stem cell transplant: virological monitoring and first-line treatment.

PubMed

Chiereghin, A; Prete, A; Belotti, T; Gibertoni, D; Piccirilli, G; Gabrielli, L; Pession, A; Lazzarotto, T

2016-02-01

In 28 pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, we aimed to evaluate: (i) the impact of routine Epstein-Barr virus (EBV) DNA monitoring on the development of EBV-related post-transplant lymphoproliferative disorder (EBV-PTLD); (ii) the incidence of EBV infection and the potential risk factors; and (iii) the suitability of whole blood (WB) as clinical specimen to monitor the risk of patients to develop EBV-PTLD. Quantitative real-time polymerase chain reaction assay was performed on WB samples for all patients. EBV DNA quantification also in peripheral blood mononuclear cells (PBMCs) samples was adopted for the patients at higher risk of developing EBV-PTLD (≥ 10,000 copies/mL WB). High EBV DNAemia levels were observed in 37.5% of the actively infected recipients (57.1%). Severe aplastic anemia, matched-unrelated donor transplant, the reduced-intensity conditioning regimen and, to a lesser extent, the in vivo T-cell depletion with anti-thymocyte immunoglobulin were associated with high viral load. A significant correlation between EBV DNA levels in WB and PBMC samples was obtained (r = 0.755, P < 0.001). A similar kinetics of EBV DNA in the 2 blood compartments was observed. Clinically, both specimen types appeared to be equally informative to assess the risk of patients to develop PTLD. On the basis of EBV DNAemia levels, in 3 patients (10.7%) immunosuppressive therapy was reduced and 1 patient (3.5%) received early treatment for probable EBV disease. No patients developed EBV-PTLD. WB proved to be a suitable clinical specimen to monitor EBV DNA load after allo-HSCT for the management of EBV infection and PTLD prevention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Angiotensin receptors as sensitive markers of acute bronchiole injury after lung transplantation.

PubMed

Nataatmadja, Maria; Passmore, Margaret; Russell, Fraser D; Prabowo, Sulistiana; Corley, Amanda; Fraser, John F

2014-08-01

Although lung transplantation is the only means of survival for patients with end-stage pulmonary disease, outcomes from this intervention are inferior to other solid organ transplants. The reason for the poor outcomes may be linked to an early reaction, such as primary graft dysfunction, and associated with marked inflammatory response, bronchiole injury, and later fibrotic responses. Mediators regulating these effects include angiotensin II and matrix metalloproteinases (MMPs). We investigated changes to these mediators over the course of cardiopulmonary bypass (CPB) and up to 72 h after lung transplantation, using immunohistochemistry, Western blot, and ELISA techniques. We found 4- and 16-fold increases in plasma angiotensin II and MMP-9, respectively, from pre-CPB to post-CPB. MMP-9 levels remained elevated 1 h after transplantation. MMP-2 levels were elevated 6-24 h after lung transplantation. Type 2 angiotensin II receptor (ATR2) expression was 3.5-fold higher in bronchoalveolar cells 1-6 h after transplantation than in controls. The study suggests that the combination of cardiopulmonary bypass and lung transplantation is associated with early changes in the angiotensin II receptor system and in MMPs, and that altered expression of these mediators may be a useful marker to examine pathological changes that occur in lungs during transplant surgery.

Monitoring of Epstein-Barr viral load in pediatric heart and lung transplant recipients by real-time polymerase chain reaction.

PubMed

Benden, Christian; Aurora, Paul; Burch, Michael; Cubitt, David; Lloyd, Cathryn; Whitmore, Pauline; Neligan, Sophie L; Elliott, Martin J

2005-12-01

Elevation in Epstein-Barr virus (EBV) load measured in peripheral blood has been proposed as a marker for development of post-transplant lymphoproliferative disease (PTLD), but there are few published data examining this relationship. We report the longitudinal surveillance of EBV for all recipients of heart (HTx), heart-lung (HLTx) and lung (LTx) transplants at our institution. The study population included all patients transplanted between January 2003 and July 2004. EBV load was serially measured in peripheral blood by real-time polymerase chain reaction (PCR). Results were correlated with recipient pre-transplant EBV status and development of PTLD. Forty-four transplant operations were performed, including 33 HTx, 6 HLTx and 5 LTx. Thirty-two (73%) of the patients were EBV seropositive pre-transplant. Nineteen (44%) pediatric recipients developed EB viremia, including 17 HTx, 1 HLTx and 1 LTx. Eleven (58%) of these patients were EBV seropositive pre-transplant. EBV was first detected at a median of 30.5 days (range 2 to 81) post-transplant. The median peak EBV load in that group was 10,099 copies/ml (range 5,935 to 255,466) whole blood. One patient with cystic fibrosis post-LTx developed PTLD localized in the colon. This patient was EBV seronegative pre-transplant; peak EBV load was 14,513 copies/ml. Acute infectious mononucleosis was seen in 1 case. Positive pre-transplant EBV status did not predict post-transplant EB viremia (positive predictive value 0.03). Contrary to earlier reports, our data demonstrate that a high EBV load does not lead to PTLD early post-transplant. These results do not support the practice of pre-emptively reducing immunosuppression in patients with raised EBV load.

Planetary period oscillations in Saturn's magnetosphere: comments on the relation between post-equinox periods determined from magnetic field and SKR emission data

NASA Astrophysics Data System (ADS)

Cowley, S. W. H.; Provan, G.

2015-07-01

We discuss the properties of Saturn planetary period oscillations (PPOs) deduced from analysis of Saturn kilometric radiation (SKR) modulations by Fischer et al. (2014), and from prior analysis of magnetic field oscillations data by Andrews et al. (2012) and Provan et al. (2013), with emphasis on the post-equinox interval from early 2010 to early 2013. Fischer et al. (2014) characterize this interval as showing single phase-locked periods in the northern and southern SKR modulations observed in polarization-separated data, while the magnetic data generally show the presence of separated dual periods, northern remaining shorter than southern. We show that the single SKR period corresponds to the southern magnetic period early in 2010, segues into the northern period in late 2010, and returns to the southern period in mid-2012, approximately in line with changes in the dominant magnetic oscillation. An exception occurs in mid-February to late August 2011 when two periods are again discerned in SKR data, in good agreement with the ongoing dual periods in the magnetic data. Fischer et al. (2014) discuss this change in terms of a large jump in the southern SKR period related to the Great White Spot storm, which the magnetic data show is primarily due instead to a reappearance in the SKR data of the ongoing southern modulation in a transitory interval of resumed southern dominance. In the earlier interval from early April 2010 to mid-February 2011 when Fischer et al. (2014) deduce single phase-locked periods, we show unequivocal evidence in the magnetic data for the presence of separated dual oscillations of approximately equal amplitude. We suggest that the apparent single SKR periods result from a previously reported phenomenon in which modulations associated with one hemisphere appear in polarization-separated data associated with the other. In the following interval, mid-August 2011 to early April 2012, when Fischer et al. (2014) again report phase-locked northern

Timing of dialysis initiation in transplant-naive and failed transplant patients

PubMed Central

Molnar, Miklos Z.; Ojo, Akinlolu O.; Bunnapradist, Suphamai; Kovesdy, Csaba P.; Kalantar-Zadeh, Kamyar

2017-01-01

Over the past two decades, most guidelines have advocated early dialysis initiation on the basis of studies showing improved survival in patients starting dialysis early. These recommendations led to an increase in the proportion of patients initiating dialysis with an estimated glomerular filtration rate (eGFR) >10 ml/min/1.73 m2, from 20% in 1996 to 52% in 2008. During this period, patients starting dialysis with an eGFR ≥15 ml/min/1.73 m2 increased from 4% to 17%. However, recent studies have failed to substantiate a benefit of early dialysis initiation and some data have suggested worse outcomes in patients starting dialysis with a higher eGFR. Several reasons for this seemingly paradoxical observation have been suggested, including the fact that patients requiring early dialysis are likely to have more severe symptoms and comorbidities, leading to confounding by indication, as well as biological mechanisms that causally relate early dialysis therapy to adverse outcomes. Dialysis reinitiation in patients with a failing renal allograft encounters similar problems. However, unique factors associated with a failed allograft means that the optimal timing of dialysis initiation in failed transplant patients might differ from that in transplant-naive patients. In this Review, we will discuss studies of dialysis initiation and compare risks and benefits of early versus late dialysis therapy. PMID:22371250

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

PubMed

Kim, Young; Stahl, Christopher C; Makramalla, Abouelmagd; Olowokure, Olugbenga O; Ristagno, Ross L; Dhar, Vikrom K; Schoech, Michael R; Chadalavada, Seetharam; Latif, Tahir; Kharofa, Jordan; Bari, Khurram; Shah, Shimul A

2017-12-01

Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein <400 ng/mL before orthotopic liver transplantation, through locoregional therapies. Recurrence of hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an

Post-transplant HLA class II antibodies and high soluble CD30 levels are independently associated with poor kidney graft survival.

PubMed

Langan, L L; Park, L P; Hughes, T L; Irish, A; Luxton, G; Witt, C S; Christiansen, F T

2007-04-01

HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p < 0.0001) when detected by ELISA, and a HR of 6.0 (p < 0.0001) when detected by Luminex. A high post-transplant sCD30 level >or=100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p < 0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.

Post-conditioning preserves glycolytic ATP during early reperfusion: a survival mechanism for the reperfused heart.

PubMed

Correa, Francisco; García, Noemí; Gallardo-Pérez, Juan; Carreno-Fuentes, Liliana; Rodríguez-Enríquez, Sara; Marín-Hernández, Alvaro; Zazueta, Cecilia

2008-01-01

Glycolytic activity during the transition period from anaerobic to aerobic metabolism has been demonstrated to be critical for heart recovery in isolated reperfused hearts. The purpose of this work was to investigate the relevance of the glycolytic pathway in preserving the cardiac function of post-conditioned hearts. The activation of the glycolytic pathway in post-conditioned hearts was evaluated by measuring GLUT-4 insertion, glucose consumption and lactate production. Iodoacetic acid and 2-deoxy-D-glucose were administrated to the working hearts to evaluate the effect of glycolytic inhibition in the post-conditioning protective effect. Post-conditioning maneuvers applied to isolated rat hearts, after prolonged ischemia and before reperfusion, promoted recovery of cardiac mechanical function with sustained increase of GLUT-4 translocation and activation of the glycolytic pathway during ischemia and early reperfusion. Iodoacetate inhibited the protective effect of post-conditioning, without affecting the mitochondrial oxidative capacity. Glycolysis contribution to maintain mechanical function at early reperfusion was observed in post-conditioned hearts perfused with 2-deoxy-D-glucose and in hearts in which iodoacetate was administered only during reperfusion. It is concluded that in the post-conditioned heart, a functional compartmentation of anaerobic energy metabolism, at early reperfusion, plays a significant role in cardiac protection against reperfusion damage. Copyright 2008 S. Karger AG, Basel.

Music therapy for early cognitive rehabilitation post-childhood TBI: an intrinsic mixed methods case study.

PubMed

Bower, Janeen; Catroppa, Cathy; Grocke, Denise; Shoemark, Helen

2014-10-01

The primary aim of this case study was to explore the behavioural changes of a paediatric patient in post-traumatic amnesia (PTA) during a music therapy session. A secondary objective was to measure the effect of the music therapy intervention on agitation. Video data from pre, during and post-music therapy sessions were collected and analysed using video micro-analysis and the Agitated Behaviour Scale. The participant displayed four discrete categories of behaviours: Neutral, Acceptance, Recruitment and Rejection. Further analysis revealed brief but consistent and repeated periods of awareness and responsiveness to the live singing of familiar songs, which were classified as Islands of Awareness. Song offered an Environment of Potential to maximise these periods of emerging consciousness. The quantitative data analysis yielded inconclusive results in determining if music therapy was effective in reducing agitation during and immediately post the music therapy sessions. The process of micro-analysis illuminated four discrete participant behaviours not apparent in the immediate clinical setting. The results of this case suggest that the use of familiar song as a music therapy intervention may harness early patient responsiveness to foster cognitive rehabilitation in the early acute phase post-TBI.