Centro de Documentación e Información en Trasplantes
(CEDIT)
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A
todos los interesados: El CEDIT.CUCAIBA
recibió y pone a su disposición, los trabajos contenidos
en la revista "Transplantation", 91(8), April 27, 2011.
Este contenido se presenta en dos formas: concitas bibliográficas
y a continuación en el mismo orden con citas bibliográficas
y resúmenes. Agradeceremos que cuando seleccionen los artículos
de su interes, en el pedido incluyan la dirección postal y
lugar de trabajo. Gracias
cedit@cucaiba.gba.gov.ar
CEDIT/
Nuevo / alertas bibilográficas
...............................................................................................................
Los
servicios pueden solicitarse
por correo, teléfono, fax o e-mail al:
Centro
de Documentación e Información en Trasplantes (CEDIT)
del CUCAIBA
E-mail: cedit@cucaiba.gba.gov.ar
Visite nuestra web: "htp://www.cucaiba.gba.gov.ar
Tel (0221) 427 6070 Interno 211
Fax (0221) 425 0400
Calle 129 e/ 51 y 53 (El Dique), Ensenada (CP 1925), Provincia de
Buenos Aires, Argentina
...............................................................................................................
El
Centro de Documentación e Información en Trasplantes
(CEDIT) del CUCAIBA Ministerio de Salud de la Provincia de Buenos
Aires se crea por una disposición ministerial, en agosto de
1999, cuando la Comisión de Educación Permanente y Apoyo
a la Investigación planteó entre sus objetivos la creación
de un Centro de Documentación en Trasplantología.
El
CEDIT participa de la Red Nacional de Información en Ciencias
de la Salud (RENICS/Argentina), Red de la Asociación de Bibliotecas
Biomédicas Argentinas (Bibliomed) y de la Red Latinoamericano
y del Caribe de Información en Ciencias de la Salud (BIREME/OPS/OMS,
San Pablo, Brasil)
El
CEDIT está especializado en temas de donación, procuración
y trasplante de órganos y tejidos, y abarca también
otras temáticas del área de la medicina, bioética
y social.
El
CEDIT surge con el objetivo de dar respuesta a los requerimientos
de capacitación y actualización de información
científica por parte de los equipos de salud de la Institución.
La complejidad de esta disciplina necesita de una educación
permanente en el área, para estar actualizados con la documentación
producida por los adelantos científicos. Por tal motivo es
importante resaltar la colaboración con los investigadores
y estudiosos en la actualización científica y en la
producción y diseminación de trabajos sobre esta temática.
El
CEDIT recibe revistas especializadas en donación, procuración
y trasplante de órganos y tejidos, documentación sobre
aspectos ético-sociales, memorias institucionales, etc., como
asimismo publicaciones internas.
...............................................................................................................
Los
servicios que presta en la actualidad son:
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Consultas
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Alerta Bibliográfica:
Se remite periódicamente por correo electrónico, las
Tablas de Contenido de las revistas de trasplante que se reciben periódicamente,
por gentileza del INCUCAI y al mismo tiempo se envían copia
de los trabajos solicitados.
-
Alerta Informativa:
Se envía periódicamente información especializada
en trasplante e información general identificada por el Cedit,
como asimismo se colabora con las distintas áreas del organismo
del cual depende en la difusión de la información y
documentación producida por el mismo.
-Búsquedas
bibliográficas:
Se efectúan búsquedas bibliografías a solicitud,
localización de documentos seleccionados y entrega de los mismos,
sobre la temática trasplantológíca.
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Actualización periódica de la Web Institucional:
Se actualiza periódicamente la página profesional de
la web institucional.
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Visitas de Estudio
Visitas de estudio de alumnos y profesores del Instituto Superior
de Formación Docente y Técnica N° 8, dependiente
de la Dirección General de Cultura y Educación de la
Provincia de Buenos Aires, para conocer la organización y funcionamiento
del Cedit. Estas visitas tienen un efecto multiplicador, porque son
propicias, para que el personal del área de difusión,
realice charlas, evacue consultas y entregue folletos.
-
Fotocopias
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Prestamos
...............................................................................................................
CEDIT/
Nuevo / alertas bibilográficas
A todos los interesados:
El CEDIT.CUCAIBA recibió y pone a su disposición, los trabajos contenidos en la revista"Transplantation", 92(12), December 27, 2011. Este contenido se presenta en dos formas: concitas bibliográficas y a continuación en el mismo orden con citas bibliográficas y resúmenes. Agradeceremos que cuando seleccionen los artículos de su interes, en el pedido incluyan la dirección postal y lugar de trabajo. Gracias cedit@cucaiba.gba.gov.ar TRANSPLANTATION 92(12), December 27, 2011
1
Peripheral blood gene expression analysis in intestinal transplantation: a feasibility study for detecting novel candidate biomarkers of graft rejection.
Andreev VP, Tryphonopoulos P, Blomberg BB, Tsinoremas N, Weppler D, Neuman DR,
Volsky A, Nishida S, Tekin A, Selvaggi G, Levi DM, Tzakis AG, Ruiz P.
Transplantation. 2011 Dec 27;92(12):1385-91.
2.
Informed consent and decision-making about adult-to-adult living donor liver transplantation: a systematic review of empirical research.
Gordon EJ, Daud A, Caicedo JC, Cameron KA, Jay C, Fryer J, Beauvais N, Skaro A,
Baker T.
Transplantation. 2011 Dec 27;92(12):1285-96.
3.
Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients.
Phipps LM, Chen SC, Kable K, Halliday CL, Firacative C, Meyer W, Wong G,
Nankivell BJ.
Transplantation. 2011 Dec 27;92(12):1327-34
4.
Associations of ABCB1 3435C>T and IL-10-1082G>A polymorphisms with long-term sirolimus dose requirements in renal transplant patients.
Sam WJ, Chamberlain CE, Lee SJ, Goldstein JA, Hale DA, Mannon RB, Kirk AD, Yi Hon
Y.
Transplantation. 2011 Dec 27;92(12):1342-7.
5.
Tolerance to vascularized composite allografts in canine mixed hematopoietic chimeras.
Mathes DW, Hwang B, Graves SS, Edwards J, Chang J, Storer BE, Butts-Miwongtum T,
Sale GE, Nash RA, Storb R.
Transplantation. 2011 Dec 27;92(12):1301-8.
6.
Temporal association between increased virus-specific Th17 response and spontaneous recovery from recurrent hepatitis C in a liver transplant recipient.
Seetharam AB, Borg BB, Subramanian V, Chapman WC, Crippin JS, Mohanakumar T.
Transplantation. 2011 Dec 27;92(12):1364-70.
7.
A possible explanation for anemia in patients treated with mycophenolic acid.
Pile T, Kieswich J, Harwood S, Yaqoob MM.
Transplantation. 2011 Dec 27;92(12):1316-21.
8
Neuropsychological functioning in patients with alcohol-related liver disease before and after liver transplantation.
Pegum N, Connor JP, Feeney GF, Young RM.
Transplantation. 2011 Dec 27;92(12):1371-7.
9
Quality of life in adult survivors of pediatric kidney transplantation.
Haavisto A, Jalanko H, Sintonen H, Holmberg C, Qvist E.
Transplantation. 2011 Dec 27;92(12):1322-6.
10
Early changes in kidney function predict long-term chronic kidney disease and mortality in patients after liver transplantation.
Cantarovich M, Tchervenkov J, Paraskevas S, Ghali P, Wong P, Deschênes M,
Chaudhury P, Hassanain M, Vrochides D, Metrakos P, Barkun J.
Transplantation. 2011 Dec 27;92(12):1358-63.
11
Joint impact of donor and recipient parameters on the outcome of liver transplantation in Germany.
Frühauf NR, Fischer-Fröhlich CL, Kutschmann M, Schmidtmann I, Kirste G.
Transplantation. 2011 Dec 27;92(12):1378-84.
12
Protection of porcine islet xenografts in mice using sertoli cells and monoclonal antibodies.
Ramji QA, Bayrack K, Arefanian H, Marcet-Palacios M, Bleackley RC, Rajotte RV,
Rayat GR.
Transplantation. 2011 Dec 27;92(12):1309-15.
13
Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation.
Ciancio G, Gaynor JJ, Sageshima J, Guerra G, Zarak A, Roth D, Brown R, Kupin W,
Chen L, Hanson L, Tueros L, Ruiz P, Livingstone AS, Burke GW 3rd.
Transplantation. 2011 Dec 27;92(12):1348-57.
14
Validity of surrogate measures for functional nephron mass.
Tan JC, Paik J, Chertow GM, Grumet FC, Busque S, Lapasia J, Desai M.
Transplantation. 2011 Dec 27;92(12):1335-41.
15
Uniform definitions for donor-derived infectious disease transmissions in solid organ transplantation.
Garzoni C, Ison MG.
Transplantation. 2011 Dec 27;92(12):1297-300.
Citas bibliográficas y resúmenes:
1
Peripheral blood gene expression analysis in intestinal transplantation: a feasibility study for detecting novel candidate biomarkers of graft rejection.
Andreev VP, Tryphonopoulos P, Blomberg BB, Tsinoremas N, Weppler D, Neuman DR,
Volsky A, Nishida S, Tekin A, Selvaggi G, Levi DM, Tzakis AG, Ruiz P.
Transplantation. 2011 Dec 27;92(12):1385-91.
INTRODUCTION: We investigated the putative candidate biomarkers of graft
rejection in peripheral blood of intestinal transplant patients.
MATERIALS AND METHODS: Peripheral blood gene expression analysis was performed in
intestinal transplant patients. The results were matched with concurrent graft
biopsies using bioinformatics.
RESULTS: Peripheral blood samples (n=11), of 3 adult patients [transplant day
(n=1), no rejection (n=1), minimal rejection (n=2), mild rejection (n=5) and
severe rejection (n=2)] were collected. Bioinformatics: Enrichment Analysis: The
three most affected pathways differentially expressed in rejection versus a pool
of healthy volunteers were related to protein translation: translation
initiation, translation elongation termination, and translation in mitochondria,
with p-values for all rejection stages in all patients in the 10-4 to 10-18
range. No significant enrichment was observed for these categories in the day of
transplant sample. In addition to translation, significant enrichment of several
immune response categories was observed in rejection samples. Subsequent gene set
enrichment analysis verified these results. The level of enrichment was very high
(p-values of 10-5-10-60) and increased with the level of rejection in all
patients. Genes significantly down-regulated in translation related gene sets
included ribosomal proteins RPL13A, RP L22, RPS23, RPL13 and RPL10A, that could
be used as potential biomarkers for future experiments.
CONCLUSION: In this pilot study we found a list of genes (involved in
translation) significantly downregulated in the peripheral blood of three
intestinal transplant patients during rejection. These results will be verified
in further studies with increased number of patients and with isolation of
peripheral blood subpopulations.
2.
Informed consent and decision-making about adult-to-adult living donor liver transplantation: a systematic review of empirical research.
Gordon EJ, Daud A, Caicedo JC, Cameron KA, Jay C, Fryer J, Beauvais N, Skaro A,
Baker T.
Transplantation. 2011 Dec 27;92(12):1285-96.
Adult-to-adult living donor liver transplantation (LDLT) is a complex procedure
that poses serious health risks to and provides no direct health benefit for the
donor. Because of this uneven risk-benefit ratio, ensuring donor autonomy through
informed consent is critical. To assess the current knowledge pertaining to
informed consent for LDLT, we conducted a systematic review of the empirical
literature on donors' decision-making process, comprehension about risks and
outcomes, and information needs for LDLT. Of the 1423 identified articles, 24 met
final review criteria, representing the perspective of approximately 2789
potential and actual donors. As donors' decisions to donate often occur before
evaluation, they often make uninformed decisions. The review found that 88% to
95% of donors reported understanding information clinicians disclosed about risks
and benefits. However, donors reported unmet information needs, knowledge gaps
regarding risks, and unanticipated complications. Few donors reported feeling
pressure to donate. Most studies were limited by cultural differences, small
sample sizes, inconsistent measures, and poor methodological approaches. This
systematic review suggests that informed consent for LDLT is sub-optimal as
donors do not adequately appreciate disclosed information during the informed
consent process, despite United Network for Organ Sharing/CMS regulations
requiring formal psychological evaluation of donor candidates. Interventions are
needed to improve donor-clinician communication during the LDLT informed consent
process such as through the use of comprehension assessment tools and e-health
educational tools that leverage adult learning theory to effectively convey LDLT
outcome data.
3.
Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients.
Phipps LM, Chen SC, Kable K, Halliday CL, Firacative C, Meyer W, Wong G,
Nankivell BJ.
Transplantation. 2011 Dec 27;92(12):1327-34
BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an important
infection-related complication, whose mode of transmission remains uncertain.
METHODS: We investigated a nosocomial cluster of 14 PJP cases (11 confirmed and 3
probable) in kidney transplant recipients using epidemiological and genotyping
methods.
RESULTS: Poisson regression calculated an incidence density ratio of 42.8 (95%
confidence interval [CI], 14.1-129.3) versus background 0.64 cases of 1000
patient-years (P<0.001). All patients presented with respiratory failure, 10
required ventilation, two died, and six transplants failed, costing $31,854 (±SD
$26,048) per patient. Four-locus multilocus sequence typing analysis using DNA
extracts from 11 confirmed cases identified two closely related genotypes, with 9
of 11 sharing an identical composite multilocus sequence typing genotype. Contact
tracing found colocalization of cases within clinic waiting areas, suggesting
person-to-person transmission. Minimal and maximal PJP incubation periods were
124±83 to 172±71 days, respectively. Oropharyngeal washes from outpatient staff
and ambient air samples were negative for P. jirovecii DNA. Cohort analysis (14
cases vs. 324 unaffected clinic control patients) identified independent risk
factors including previous cytomegalovirus infection (odds ratio [OR], 65.9; 95%
CI, 7.9-550; P<0.001), underlying pulmonary disease (OR, 10.1; 95% CI, 2.3-45.0;
P=0.002), and transplant dysfunction (OR=1.61 per 10 mL/min/1.73 m, 95% CI,
1.15-2.25, P=0.006). The outbreak was controlled by reintroduction of
trimethoprim/sulfamethoxazole prophylaxis to all potentially exposed clinic
patients and its extension to 12 months in recent recipients.
CONCLUSIONS: Nosocomial PJP clusters are likely due to interhuman transmission by
airborne droplets to susceptible hosts. Prompt recognition and a strategy of
early preemptive blanket PJP prophylaxis to all exposed transplant clinic
recipients from the third confirmed case are recommended to limit outbreak
escalation.
4.
Associations of ABCB1 3435C>T and IL-10-1082G>A polymorphisms with long-term sirolimus dose requirements in renal transplant patients.
Sam WJ, Chamberlain CE, Lee SJ, Goldstein JA, Hale DA, Mannon RB, Kirk AD, Yi Hon
Y.
Transplantation. 2011 Dec 27;92(12):1342-7.
BACKGROUNDS: Sirolimus (SRL) absorption and metabolism are affected by
p-glycoprotein-mediated transport and CYP3A enzyme activity, which are further
under the influences of cytokine concentrations. This retrospective study
determined the associations of adenosine triphosphate-binding cassette, subfamily
B, member 1 (ABCB1) 1236C>T, 2677 G>T/A, and 3435C>T, cytochrome P450, family 3,
subfamily A, polypeptide 4 (CYP3A4) -392A>G, cytochrome P450, family 3, subfamily
A, polypeptide 5 (CYP3A5) 6986A>G and 14690G>A, interleukin (IL)-10 -1082G>A, and
tumor necrosis factor (TNF) -308G>A polymorphisms with SRL dose-adjusted,
weight-normalized trough concentrations (C/D) at 7 days, and at 1, 3, 6, and 12
months after initiation of SRL.
METHODS: Genotypes for 86 renal transplant patients who received SRL-based
maintenance immunosuppressive therapy were determined using polymerase chain
reaction followed by chip-based mass spectrometry. The changes of log-transformed
C/D over the days posttransplantation were analyzed using a linear mixed-effects
model, with adjustments for body mass index and weight-normalized doses of
tacrolimus, prednisone, clotrimazole, and statins.
RESULTS: ABCB1 3435C>T and IL-10 -1082G>A were significantly associated with log
C/D (P=0.0016 and 0.0394, respectively). Mean SRL C/D was 48% higher in patients
with ABCB1 3435CT/TT genotype than those with 3435CC genotype, and was 24% higher
in IL-10 -1082GG compared with -1082AG/AA.
CONCLUSIONS: ABCB1 3435C>T and IL-10 -1082G>A were significantly associated with
long-term SRL dose requirements. Genetics can play a significant role in SRL
dosing and may be useful in therapeutic monitoring of SRL in renal
transplantation. Future replication studies are needed to confirm these
associations.
5.
Tolerance to vascularized composite allografts in canine mixed hematopoietic chimeras.
Mathes DW, Hwang B, Graves SS, Edwards J, Chang J, Storer BE, Butts-Miwongtum T,
Sale GE, Nash RA, Storb R.
Transplantation. 2011 Dec 27;92(12):1301-8.
BACKGROUND: Mixed donor-host chimerism, established through hematopoietic cell
transplantation (HCT), is a reproducible strategy for the induction of tolerance
toward solid organs. Here, we ask whether a nonmyeloablative conditioning regimen
establishing mixed donor-host chimerism leads to tolerance of antigenic
vascularized composite allografts.
METHODS: Stable mixed chimerism was established in dogs given a sublethal dose
(1-2 Gy) total body irradiation before and a short course of immunosuppression
after dog leukocyte antigen-identical marrow transplantation. Vascularized
composite allografts from marrow donors were performed after a median of 36
months (range, 4-54 months) after HCT.
RESULTS: All marrow recipients maintained mixed donor-host hematopoietic
chimerism and accepted vascularized composite allografts for periods ranging
between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite
allografts from their respective marrow recipients within 18 to 29 days. Biopsies
of muscle and skin of vascularized composite allografts from mixed chimeras
showed few infiltrating cells compared with extensive infiltrates in biopsies of
vascularized composite allografts from marrow donors. Elevated levels of CD3+
FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite
allografts of mixed chimeras compared with normal tissues. In mixed chimeras,
increased numbers of T-regulatory cells were found in draining compared with
nondraining lymph nodes of vascularized composite allografts.
CONCLUSIONS: These data suggest that nonmyeloablative HCT may form the basis for
future clinical applications of solid organ transplantation and that T-regulatory
cells may function toward maintenance of the vascularized composite allograft.
6.
Temporal association between increased virus-specific Th17 response and spontaneous recovery from recurrent hepatitis C in a liver transplant recipient.
Seetharam AB, Borg BB, Subramanian V, Chapman WC, Crippin JS, Mohanakumar T.
Transplantation. 2011 Dec 27;92(12):1364-70.
BACKGROUND: Spontaneous clearance of hepatitis C virus (HCV) after orthotopic
liver transplantation (OLT) is a rare occurrence. Here, we present detailed
immunological analysis of an interferon naive OLT recipient receiving
uninterrupted immunosuppression who cleared HCV spontaneously 2 years after
transplantation.
METHODS: Enzyme-linked immunospot assay analysis of peripheral T-cell interferon
gamma (IFN-γ), interleukin (IL)-10, and IL-17 response to HCV core and
nonstructural antigen 4 and enzyme-linked immunosorbent assay (ELISA) to collagen
(Col) subtypes I, II, IV, and V were performed in the index patient at the time
of viral clearance and compared with an OLT cohort with persistent viremia
matched for time from OLT, immunosuppression, and histology. Enzyme-linked
immunospot assay and ELISA analysis were repeated on the patient 4 years after
OLT. Transcription-mediated amplification assays were used to confirm viral
clearance.
RESULTS: Compared with a cohort of post-OLT and nontransplanted viremic HCV
patients, the index patient with HCV clearance demonstrated higher IL-17, IL-10,
and lower IFN-γ response to nonstructural antigen 4 and core antigen and a higher
titer of antibodies (Abs) to Col subtypes I, II, and V during clearance. On
follow-up 2 years later, HCV-specific IFN-γ was increased in the index patient,
with a decline in IL-17 and IL-10 response and Col I, II, and V Ab titer.
CONCLUSIONS: Virus-induced activation of Th-17 cells may contribute to HCV
clearance post-OLT. Maintenance of viral suppression may be facilitated by
restoration of Th1 (IFN-γ) responses. Modulation of Th17 immunity deserves
further attention as a therapeutic strategy in the treatment of HCV recurrence
post-OLT.
7.
A possible explanation for anemia in patients treated with mycophenolic acid.
Pile T, Kieswich J, Harwood S, Yaqoob MM.
Transplantation. 2011 Dec 27;92(12):1316-21.
BACKGROUND: Clinical studies suggest that the immunosuppressant mycophenolate
mofetil is associated with anemia. However, the mechanism for this is not known.
Here, we studied the effect of mycophenolic acid (MPA), the active metabolite of
mycophenolate mofetil, on erythropoiesis in vitro.
METHODS: Both UT-7 cells and primary murine bone marrow cells were studied. Cells
were initially treated with erythropoietin and MPA and proliferation and
caspase-3 assays were performed. The effect of guanosine-5'-triphosphate,
guanosine, and caspase inhibitors was also investigated.
RESULTS: MPA was found to decrease the proliferation of UT-7 cells and
erythropoiesis in murine bone marrow cells. This inhibition was associated with
an increase in caspase-3 activity in the UT-7 cells. Inhibition was reversed in
UT-7 cells and in murine bone marrow by guanosine, but not by caspase inhibitors.
The apoptosis induced by MPA was also reversed by guanosine. UT-7 cells treated
with MPA showed a decreased inosine-5'-monophosphate dehydrogenase activity.
CONCLUSION: These results suggest that MPA inhibits inosine-5'-monophosphate
dehydrogenase activity in erythroid cells and that this is a likely mechanism of
action of anemia in MPA-treated patients.
8
Neuropsychological functioning in patients with alcohol-related liver disease before and after liver transplantation.
Pegum N, Connor JP, Feeney GF, Young RM.
Transplantation. 2011 Dec 27;92(12):1371-7.
BACKGROUND: Cognitive dysfunction is common in both end-stage liver disease and
chronic alcohol misuse. The impact of orthotopic liver transplantation (OLT) on
neuropsychological function is poorly documented. This prospective study examined
changes in cognitive function pre- and post-OLT in patients with alcohol-related
liver disease (ALD).
METHODS: Comprehensive neuropsychological assessment was conducted with 92
abstinent patients with ALD scheduled for OLT. Forty-two patients were available
for reassessment 12 months post-OLT.
RESULTS: Posttransplantation, cognitive performance on all measures fell within
normal limits. Greatest improvement occurred in visuomotor speed, complex visual
attention processes, and the ability to solve visually presented problems.
Performance on memory assessment tasks also improved posttransplantation.
Applying a more robust assessment of change (Reliable Change Index),
approximately half improved reliably on overall cognitive function. One quarter
improved in memory performance. With the exception of the Full-Scale Intelligence
Quotient scales, discriminant analysis was unable to successfully predict which
patients reliably improved.
CONCLUSIONS: Overall improvement in cognitive function occurs after liver
transplantation in ALD. It was not possible to identify which patient
characteristics were associated with reliable change.
9
Quality of life in adult survivors of pediatric kidney transplantation.
Haavisto A, Jalanko H, Sintonen H, Holmberg C, Qvist E.
Transplantation. 2011 Dec 27;92(12):1322-6.
BACKGROUND: There are few studies assessing long-term adult outcome and
health-related quality of life (HRQOL) in former pediatric high-risk kidney
transplant (TX) recipients.
METHODS: Twenty-one patients were assessed at mean age of 21.1 years. Mean age at
first TX was 2.4 years. Brain arterial border zone infarcts had been documented
in 54% of the children. HRQOL was assessed with the general 15-dimensional (15D)
instrument generating an index on a 0 and 1 scale (1 for best). The results were
compared with the corresponding childhood 17-dimensional instrument and an adult
control group from the general population. Psychosocial adjustment was assessed
with the ASEBA Adult Self Report (ASR) and compared with the childhood Child
Behavior Checklist assessments.
RESULTS: Half of the patients (52%) had a secondary level general or vocational
education. The educational outcome was evenly distributed (compulsory vs.
secondary) regardless of previous childhood brain ischemia. The ASR Total
Problems score was in the normal range for all patients. Four patients had scores
in the pathological range for Externalizing or Internalizing Problems. There was
a correlation between the childhood Child Behavior Checklist problem scores and
the adult ASR scores for Internalizing and Total Problems but not for
Externalizing Problems. Their mean 15D HRQOL index was 0.94 and lower than for
the control group (0.97, P=0.04). There was a strong correlation between the
childhood 17-dimensional and the adult 15D HRQOL index (r=0.63, P=0.003).
CONCLUSION: The long-term outcome is fair in former high-risk pediatric TX
patients with neurological comorbidity. Childhood psychosocial adjustment and
HRQOL may predict the outcome in adults.
10
Early changes in kidney function predict long-term chronic kidney disease and mortality in patients after liver transplantation.
Cantarovich M, Tchervenkov J, Paraskevas S, Ghali P, Wong P, Deschênes M,
Chaudhury P, Hassanain M, Vrochides D, Metrakos P, Barkun J.
Transplantation. 2011 Dec 27;92(12):1358-63.
BACKGROUND: Chronic kidney disease (CKD) is a well-known complication after liver
transplantation (LT) and is associated with increased mortality. The purpose of
this study was to determine risk factors of advanced CKD and mortality after LT.
METHODS: Four hundred forty-five adult patients underwent LT between June 1990
and September 2007 and survived more than 1 month. Multivariate Cox regression
analyses were performed for time to CKD stage 4 (glomerular filtration rate [GFR]
≤30 mL/min), time to chronic dialysis, and all-cause mortality. Several patient
and disease characteristics were used as independent pre- and posttransplant
variables. We specifically analyzed a drop more than or equal to 30% in the
estimated GFR (eGFR) during the first year posttransplant.
RESULTS: Diabetes mellitus pretransplant and a drop more than or equal to 30% in
the eGFR between 3 and 12 months predicted CKD stage 4 (odds ratio [OR] 4.1, 95%
confidence interval [CI] 1.9-5.4, P<0.001 and OR 16.1, 95% CI 5.9-44.5, P<0.0001,
respectively), the need for chronic dialysis (OR 3.8, 95% CI 1.1-13.2, P=0.03 and
OR 14.6, 95% CI 3.0-71.4, P<0.001, respectively), and all-cause mortality (OR
1.9, 95% CI 1.2-2.9, P=0.004 and OR 2.6, 95% CI 1.6-4.4, P<0.001, respectively),
more than 1 year after LT.
CONCLUSIONS: Diabetes mellitus pretransplant and a drop more than or equal to 30%
in the eGFR within the first year are strong predictors of advanced CKD, chronic
dialysis, and death more than 1 year after LT. These easily determined clinical
variables define a population at risk for CKD who should be targeted for renal
protection strategies.
11
Joint impact of donor and recipient parameters on the outcome of liver transplantation in Germany.
Frühauf NR, Fischer-Fröhlich CL, Kutschmann M, Schmidtmann I, Kirste G.
Transplantation. 2011 Dec 27;92(12):1378-84.
BACKGROUND: The shortage of donor organs in Germany has led to the use of organs
from donors with extended donor criteria (EDC). EDC have been defined on the
basis of expert opinions, but their clinical relevance is controversial. This may
cause loss of organs otherwise available for transplantation. We evaluated the
impact of donor and recipient factors in liver transplants on patient and graft
survival in a nationwide multicenter analysis, with special focus on EDC and
donor risk index.
METHODS: A database was created from data on livers donated and transplanted in
Germany between 2006 and 2008 as provided by Deutsche Stiftung Organ
transplantation and BQS Institute. Cox regression (significance level 5%, risk
ratio [95% confidence interval]) was used for calculating the impact on patient
survival (n=2095) and on graft survival (n=2175).
RESULTS: Patient and graft survival were significantly affected only by donor age
(1.012 and 1.011/year), recipient age (1.019 and 1.014/year), creatinine (1.248
and 1.205/mg/dL), bilirubin (1.022 and 1.023/mg/dL), and high urgency status
(1.783 and 1.809). Inferior organ quality resulted in lower graft survival
(1.243) and donor history of smoking in lower patient survival (1.249).
CONCLUSION: Multiple Cox regression revealed no significant impact of EDC or
donor risk index on patient and graft survival except for donor age after donor
selection at recovery. Among recipient variables, only age, creatinine and
bilirubin, and high urgency status were associated with poorer outcome.
12
Protection of porcine islet xenografts in mice using sertoli cells and monoclonal antibodies.
Ramji QA, Bayrack K, Arefanian H, Marcet-Palacios M, Bleackley RC, Rajotte RV,
Rayat GR.
Transplantation. 2011 Dec 27;92(12):1309-15.
BACKGROUND: To remedy the shortage of human donor islets, xenotransplantation of
neonatal porcine islets (NPI) provides an attractive alternative source of donor
tissue so long as graft rejection can be circumvented. Thus, in this study, we
sought to determine whether cotransplantation of NPI with Sertoli cells (SC)
combined with a short-course treatment of monoclonal antibody (mAb) could provide
long-term islet xenograft survival.
METHODS: NPI alone or NPI cotransplanted with neonatal porcine SC were
transplanted into diabetic C57BL/6 mice. These mice were left untreated or were
treated with a short course of antileukocyte function associated antigen-1
(LFA-1), anti-CD154, or anti-CD45RB mAb. Blood glucose levels were monitored
twice a week to assess graft function. At more than 100 days posttransplantation
or on the day of rejection, graft-bearing kidneys were collected for
characterization using immunohistochemistry.
RESULTS: None of the untreated control mice transplanted with NPI alone (0/5) or
NPI cotransplanted with SC (0/8) achieved normoglycemia. However, of the mice
receiving NPI alone, 3 of 7 treated with anti-LFA-1 mAb, 2 of 7 treated with
anti-CD154 mAb, and 1 of 7 treated with anti-CD45RB mAb achieved long-term graft
survival (>100 days). These proportions improved considerably when NPI were
cotransplanted with SC, as 15 of 15 mice treated with anti-LFA-1 mAb, 7 of 8 mice
treated with anti-CD154 mAb, and 4 of 9 mice treated with anti-CD45RB mAb
achieved long-term graft survival.
CONCLUSIONS: These results show that transient administration of anti-LFA-1 mAb
or anti-CD154 mAb is efficacious in prolonging NPI xenograft survival when islets
are cotransplanted with SC. Interleukin-4 and Serpina3n may be important
mediators of protection observed in this model.
13
Randomized trial of dual antibody induction therapy with steroid avoidance in renal transplantation.
Ciancio G, Gaynor JJ, Sageshima J, Guerra G, Zarak A, Roth D, Brown R, Kupin W,
Chen L, Hanson L, Tueros L, Ruiz P, Livingstone AS, Burke GW 3rd.
Transplantation. 2011 Dec 27;92(12):1348-57.
BACKGROUND: Given our previous experience using dual-induction therapy with
antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used
alone), we chose to compare two distinct dual-induction strategies.
METHODS: Single-center, open-label randomized trial of 200 primary kidney
transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac
doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance
consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate
sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS
dosing was targeted in group II to avoid severe leukopenia previously seen with
alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte
depletion while simultaneously allowing reduced maintenance immunosuppression.
Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR).
RESULTS: With median follow-up of 38 months, there were no differences in BPAR
rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100
(excluding borderline) in groups I and II, respectively (nonsignificant).
Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83%
in group II (N.S.). Mean estimated glomerular filtration rate (±standard error)
at 36 months was 72.1±3.3 vs. 67.5±3.3 in groups I and II (N.S.). Greater
incidence of leukopenia occurred in group II at month 1 only (P=0.002).
Percentages having EC-MPS withheld/discontinued due to leukopenia,
gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100
in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively
(P=0.01). Rates of new onset diabetes mellitus after transplantation and
infections were equally low in both groups (no lymphoproliferative disorders were
observed).
CONCLUSIONS: These two distinct dual-induction therapies with rTd, EC-MPS, and
planned early corticosteroid withdrawal resulted in favorable rates of BPAR and
all secondary outcomes.
14
Validity of surrogate measures for functional nephron mass.
Tan JC, Paik J, Chertow GM, Grumet FC, Busque S, Lapasia J, Desai M.
Transplantation. 2011 Dec 27;92(12):1335-41.
BACKGROUND: Transplanted nephron mass is an important determinant of long-term
allograft survival, but accurate assessment before organ retrieval is
challenging. Newer radiologic imaging techniques allow for better determination
of total kidney and cortical volumes.
METHODS: Using volume measurements reconstructed from magnetic resonance or
computed tomography imaging from living donor candidates, we characterized total
kidney (n=312) and cortical volumes (n=236) according to sex, age, weight,
height, body mass index (BMI), and body surface area (BSA).
RESULTS: The mean cortical volume was 204 mL (range 105-355 mL) with no
significant differences between left and right cortical volumes. The degree to
which existing anthropomorphic surrogates predict nephron mass was quantified,
and a diligent attempt was made to derive a better surrogate model for nephron
mass. Cortical volumes were strongly associated with sex and BSA, but not with
weight, height, or BMI. Four prediction models for cortical volume constructed
using combinations of age, sex, race, weight, and height were compared with
models including either BSA or BMI.
CONCLUSIONS: Among existing surrogate measures, BSA was superior to BMI in
predicting renal cortical volume. We were able to construct a statistically
superior proxy for cortical volume, but whether relevant improvements in
predictive accuracy could be gained needs further evaluation in a larger
population.
15
Uniform definitions for donor-derived infectious disease transmissions in solid organ transplantation.
Garzoni C, Ison MG.
Transplantation. 2011 Dec 27;92(12):1297-300.
High-profile cases of infectious diseases transmitted from organ donors to
transplant recipients, such as the transmission of human immunodeficiency virus,
have driven policy globally. Many nations have or are developing regulations
requiring reporting and investigation of such disease transmissions as part of
broader biovigilance programs for all substances of human origin. A group of
experts (see Acknowledgments) developed definitions for proven, probable,
possible, unlikely, excluded, intervened upon without documented transmission,
and positive assay without apparent disease transmission events that should be
used, as a starting point, to standardize nomenclature and facilitate global
tracking and study of such infectious disease transmissions.
