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1.
J Patient Saf ; 17(5): e367-e372, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-27642689

RESUMEN

ABSTRACT: After a number of high-profile incidents and national reports, it has become clear that all health professionals and all medical students must be able to raise concerns about a colleague's behavior if this behavior puts patients, colleagues, or themselves at risk.Detailed evidence from medical students about their confidence to raise concerns is limited, together with examples of barriers, which impair their ability to do so. We describe a questionnaire survey of medical students in a single-center, examining self-reported confidence about raising concerns in a number of possible scenarios. Thematic analysis was applied to comments about barriers identified.Although 80% of respondents felt confident to report a patient safety issue, students were less confident around issues of probity, attitude, and conduct. This needs to be addressed to create clear mechanisms to raise concerns, as well as support for students during the process.


Asunto(s)
Estudiantes de Medicina , Actitud del Personal de Salud , Personal de Salud , Humanos , Seguridad del Paciente , Encuestas y Cuestionarios
2.
Transplantation ; 102(12): 2065-2071, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29781954

RESUMEN

BACKGROUND: The potential for clinical trials to impact patient care may be limited if the outcomes reported vary by trial and lack direct relevance to patients. Despite the many trials conducted in kidney transplantation, premature death due to cardiovascular disease, infection, and malignancy remains high. We aimed to assess the range and consistency of outcomes reported in trials in kidney transplantation. METHODS: We searched for randomized trials conducted in kidney transplantation. We extracted the outcome measures, classified them into outcome domains, and into categories (clinical, surrogate or patient-reported outcome [PRO]). We assessed the measures used for the top 4 domains. RESULTS: Overall, 397 trials reported 12 047 outcomes measures and time points (median, 19 per trial; interquartile range, 9-42) across 106 different domains, of which 55 (52%) were surrogate, 35 (33%) clinical, and 16 (15%) PRO. The 4 most frequently reported were graft function (322 [81%] trials, 118 outcome measures), acute rejection (234 [59%], 93 measures), graft loss (215 [54%], 48 measures), and mortality (204 [51%], 51 measures). The remaining 102 domains were reported in less than 50% of trials. CONCLUSIONS: Mortality- and graft-related outcome domains were frequently reported and assessed with a multiplicity of measures. Most outcome domains were surrogate outcomes, and the reporting of relevant life-threatening complications and PRO were uncommon. Establishing core outcomes based on the shared priorities of patients/caregivers and health professionals in kidney transplantation may improve the relevance and consistency of outcome reporting in trials to better inform clinical decision making.


Asunto(s)
Determinación de Punto Final , Trasplante de Riñón , Medición de Resultados Informados por el Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Determinación de Punto Final/normas , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Trasplante de Riñón/normas , Complicaciones Posoperatorias/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Proyectos de Investigación/normas , Resultado del Tratamiento
3.
Transplantation ; 101(8): 1887-1896, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28737661

RESUMEN

BACKGROUND: Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. METHODS: We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. RESULTS: Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders-inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. CONCLUSIONS: Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.


Asunto(s)
Ensayos Clínicos como Asunto/normas , Consenso , Técnica Delphi , Trasplante de Riñón/normas , Nefrología/normas , Humanos , Resultado del Tratamiento
4.
Transplantation ; 101(8): 1875-1886, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28738403

RESUMEN

BACKGROUND: Inconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals. METHODS: In a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During rounds 2 and 3, participants rerated the outcomes after reviewing their own score, the distribution of the respondents' scores, and comments. We calculated the median, mean, and proportion rating 7 to 9 (critically important), and analyzed comments thematically. RESULTS: One thousand eighteen participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed round 1, and 779 (77%) completed round 3. The top 8 outcomes that met the consensus criteria in round 3 (mean, ≥7.5; median, ≥8; proportion, >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin), and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to 6 outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified 5 themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps. CONCLUSIONS: Graft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation.


Asunto(s)
Cuidadores/normas , Ensayos Clínicos como Asunto/normas , Consenso , Técnica Delphi , Personal de Salud/normas , Trasplante de Riñón/normas , Evaluación de Resultado en la Atención de Salud , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
5.
Transplant Direct ; 2(6): e79, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27500269

RESUMEN

BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes.

6.
Clin Kidney J ; 8(5): 623-8, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26413291

RESUMEN

BACKGROUND: Black, Asian and minority ethnic (BAME) communities are disproportionately affected by inequalities in transplant services in the UK. There are some indications from pilot programmes that appeals for BAME organ donors may be more effectively communicated by employing grassroots, community-networking approaches, but such initiatives have not been adequately described or evaluated. METHODS: Lay individuals from BAME communities were trained as peer outreach workers. They attended a series of public events to promote knowledge of organ donation and transplantation among the public. Information was gathered from 806 evaluation forms completed by event attendees at 34 separate events. From these, 54 follow-up interviews were conducted with event attendees who completed evaluation forms, indicated that they intended to sign up to the NHS Organ Donor Register (ODR) within the next month and consented to follow-up. RESULTS: Peer outreach initiatives of the type evaluated are associated with increased numbers of BAME people registering as organ donors. A total of 8.8% of event attendees signed up to the NHS ODR. The programme was most effective with people who had previously considered becoming organ donors but who did not know how to go about it. It was less effective with people who had not previously considered it, or who were scared about signing up, or who feared family or religious disapproval. CONCLUSIONS: Peer outreach programmes with BAME communities can be an effective way of reducing inequalities by increasing the number of people on the NHS ODR and encouraging people to think about the issue.

7.
Clin Transplant ; 27(3): 359-67, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23406516

RESUMEN

BACKGROUND: The shortage of organs donated for transplantation is particularly severe among ethnic minorities. Previous work has often studied ethnic minorities in broad groups, failing to differentiate by age or country of education. We investigated the younger generation of UK-educated ethnically Indian and Pakistani students to determine their attitudes toward organ donation. METHODS: We conducted nine focus groups and eight semi-structured interviews. Participants were divided by ethnicity, gender, and medical/non-medical background. Interview transcripts were analyzed by thematic analysis. RESULTS: Six key factors influencing attitudes toward organ donation were found: religion, awareness of the importance of donation, impact of medical education, culture-specific factors, treatment of donors and their organs, and influence of family. The attitude of Islam to donation was highly relevant to Pakistani participants, more than other factors; for Indians, all six factors were similarly relevant. We found that medical education specifically had an important effect on shaping attitudes toward donation. Cultural changes suggested the younger generation may differ from their elders as they adopt British culture. Awareness of donation was universally low. CONCLUSIONS: Indian and Pakistani students are hesitant to donate organs because of multiple factors, which if addressed in a culturally relevant manner could substantially improve donation rates.


Asunto(s)
Actitud , Conocimientos, Actitudes y Práctica en Salud , Trasplante de Órganos , Estudiantes de Medicina/psicología , Obtención de Tejidos y Órganos , Adolescente , Adulto , Femenino , Humanos , India , Masculino , Pakistán , Encuestas y Cuestionarios , Reino Unido , Universidades , Adulto Joven
8.
Transplantation ; 95(2): 341-6, 2013 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-23197178

RESUMEN

BACKGROUND.: Donor-specific anti-HLA antibodies (DSA) are a major cause of alloimmune injury. Transplant recipients with negative complement-dependent cytotoxic crossmatch (CDC-XM) and donor cell-based flow cytometric crossmatch (flow-XM) but low level DSA (i.e., by Luminex) have worse outcomes compared with nonsensitized patients. The aim of this study was to establish whether complement-activating ability in this low-level DSA, present before transplantation, as determined by this technique is important in dictating pathogenicity. METHODS.: We retrospectively studied 52 patients with preformed DSA detected by single-antigen flow cytometric fluorescent beads (SAFBs). Patients were transplanted using a steroid-sparing regimen consisting of alemtuzumab induction, 1 week of corticosteroids and tacrolimus monotherapy.Fifteen (29%) of 52 patients experienced antibody-mediated rejection (AMR), whereas 37 (71%) patients did not. There were no demographic differences between patients with AMR and those without. Pretransplant sera were retested using a modified (SAFB) assay, which detects the presence of the complement fragment C4d as a result of DSA-induced complement activation. RESULTS.: C4d+DSA were detected in 10 (19%) of 52 patients. Biopsy-proven AMR occurred in 7 (70%) of the 10 patients with C4d+DSA and in 8 (19%) of 42 patients with C4d-DSA. AMR-free survival was worse in patients with C4d+DSA (P<0.001). CONCLUSIONS.: The ability of preformed, low-level, DSA to trigger C4d fixation in vitro in patients with negative conventional crossmatch tests is predictive for AMR. C4d SAFB is potentially a powerful tool for risk stratification prior to transplantation and may allow identification of unacceptable donor antigens, or patients who may require enhanced immunosuppression.


Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos , Activación de Complemento , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Histocompatibilidad , Isoanticuerpos/sangre , Trasplante de Riñón/inmunología , Adulto , Biomarcadores/sangre , Biopsia , Complemento C4b , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Citometría de Flujo , Rechazo de Injerto/mortalidad , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fragmentos de Péptidos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
9.
Transplantation ; 94(7): e42, 2012 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-23210131
10.
Transplantation ; 93(9): 860-4, 2012 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-22411561

RESUMEN

Transplantation research is complex because of consent being required from several individuals, the multiplicity of sites at which donation may occur, its unpredictability, and the time constraints. It is also constrained by a tight regulatory framework, which seems to be stifling research in the United Kingdom. In this article, we recommend that (1) donor consent forms be expanded to include consent to research on organs and associated retrieved material, contemporaneously and in the future, (2) if a research intervention occurs before a recipient is identified, the organ may subsequently be offered on a "take it or leave it" basis, (3) if a research intervention occurs after a recipient is identified, that recipient has the "right of veto" on the research, (4) patients should be able to participate in more than one trial at a time, if clinically appropriate, (5) a Research Ethics Committee with specific transplantation expertise should be established, (6) the unduly onerous legal obstacles erected by the Human Tissue Act (2004) should be removed, and (7) the Organ Donor Register should be expanded to include potential donor wishes on research.


Asunto(s)
Investigación Biomédica , Consentimiento Informado/legislación & jurisprudencia , Donantes de Tejidos , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Humanos , Consentimiento Informado/ética , Donantes de Tejidos/ética , Donantes de Tejidos/legislación & jurisprudencia , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/ética , Reino Unido
11.
Transplantation ; 93(4): 348-53, 2012 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-22258288

RESUMEN

Deciding to use an organ from a donor with a primary central nervous system (CNS) tumor necessitates offsetting the risk of tumor transmission with the chances of survival if the patient waits for another offer of a transplant. Published data vary in the quoted risk of tumor transmission. We used data obtained by reviewing 246 UK recipients of organs taken from donors with CNS tumors and found no evidence of a difference in overall patient mortality for recipients of a kidney, liver, or cardiothoracic organ, compared with recipients of organs from donors without a CNS tumor. Recent publication of the UK experience of transplanting organs from CNS tumor donors found no transmission in 448 recipients of organs from 177 donors with a primary CNS tumor (Watson et al., Am J Transplant 2010; 10: 1437). This 0% transmission rate is associated with an upper 95% confidence interval limit of 1.5%. Using a series of assumptions of risk, we compared the risks of dying as a result of the transmission of a primary brain tumor with the risks of dying if not transplanted. On this basis, the use of kidneys from a donor with a primary CNS tumor provides a further 8 years of life over someone who waited for a donor who did not have a primary CNS tumor, in addition to the life years gained by the transplant itself. The benefits for the recipients of livers and cardiothoracic organs were less, but there was no disadvantage in the impact on life expectancy.


Asunto(s)
Neoplasias del Sistema Nervioso Central/complicaciones , Trasplante de Corazón/mortalidad , Trasplante de Riñón/mortalidad , Trasplante de Hígado/mortalidad , Donantes de Tejidos , Trasplante , Humanos , Esperanza de Vida , Evaluación de Resultado en la Atención de Salud , Factores de Riesgo , Tasa de Supervivencia , Obtención de Tejidos y Órganos , Listas de Espera
12.
Kidney Int ; 81(2): 170-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21918502

RESUMEN

Fas ligand is a well-known inducer of apoptosis in cells expressing its receptor Fas; it also prevents autoimmunity by inducing apoptosis of activated T cells. However, Fas ligand also mediates non-apoptotic functions involving inflammatory cell migration and cytokine responses. We sought here to study the role of Fas ligand in nephrotoxic nephritis, a model of crescentic glomerulonephritis, using generalized lymphoproliferative disorder (GLD) mice on a C57BL/6 background, which have defective Fas ligand and display only mild autoimmunity. These mice were significantly protected from glomerular crescent formation, glomerular thrombosis, renal impairment, and albuminuria 15 days after the induction of glomerulonephritis in comparison with wild-type mice. There were a reduced number of apoptotic cells in the glomeruli of nephritic GLD mice but no defect in their antibody responses or splenocyte proliferation at 15 days following the induction of glomerulonephritis. Bone marrow transplantation from wild-type mice restored disease susceptibility to GLD mice; however, wild-type mice were not protected when transplanted with bone marrow from GLD mice. Mesangial cells express Fas ligand in vitro, and these cells isolated from GLD mice produced lower amounts of monocyte chemoattractive protein-1 following interleukin-1 stimulation compared with cells from wild-type mice. Thus, Fas ligand-defective mice are protected from nephrotoxic nephritis, a disease in which both circulating and intrinsic renal cells appear to have a role.


Asunto(s)
Proteína Ligando Fas/genética , Proteína Ligando Fas/metabolismo , Glomerulonefritis/metabolismo , ARN Mensajero/metabolismo , Albuminuria/genética , Animales , Apoptosis/genética , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Trasplante de Médula Ósea , Células Cultivadas , Quimiocina CCL2/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades/inmunología , Susceptibilidad a Enfermedades/metabolismo , Glomerulonefritis/genética , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Inmunoglobulinas , Inmunotoxinas , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/metabolismo , Células Mesangiales/metabolismo , Ratones , Ratones Endogámicos C57BL , Trombosis/genética
13.
Nephrol Dial Transplant ; 27(6): 2517-25, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22167592

RESUMEN

BACKGROUND: There are many views regarding the initiation of the process for live donor kidney transplantation (LDKT), the motives of the donor and the appropriate ways to promote LDKT. METHODS: Health care professionals and patients were recruited in a tertiary renal and transplant centre and completed an anonymous questionnaire. They were then divided into focus groups and a structured interview was performed in order to discover the rationale behind the answers in the questionnaire. RESULTS: Four hundred and sixty-four participants completed the questionnaire. There were 168 health care professionals and 296 patients. Most of the participants (26.9%) suggested that the first approach to a potential donor should be made by the potential recipient. Participants believed that the most important motives for a kidney donor are relief as a result of the recipient's improved health after the transplant (82.5%) and altruism (80.4%). About 89.2% of participants believed that proper long-term medical follow-up of the donor is the most important factor for LDKT promotion. Fifty-five participants discussed the rationale of their answers in the focus group interview. CONCLUSIONS: In our study, participants preferred an initial approach of the donor by the recipient. The relief as a result of the recipient's improved health was suggested as a very strong motive for donation. Proper donor follow-up was considered to be paramount for the further development of LDKT.


Asunto(s)
Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Fallo Renal Crónico/cirugía , Trasplante de Riñón/psicología , Donadores Vivos/psicología , Donadores Vivos/estadística & datos numéricos , Médicos/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Altruismo , Comunicación , Cultura , Femenino , Grupos Focales , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/psicología , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Cuidados Preoperatorios , Pronóstico , Encuestas y Cuestionarios , Factores de Tiempo , Adulto Joven
14.
Transplantation ; 92(7): 774-80, 2011 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-21836540

RESUMEN

BACKGROUND: Immunosuppressive regimens for kidney transplantation which reduce the long-term burden of immunosuppression are attractive, but little data are available to judge the safety and efficacy of the different strategies used. We tested the hypothesis that the simple, cheap, regimen of alemtuzumab induction combined with tacrolimus monotherapy maintenance provided equivalent outcomes to the more commonly used combination of interleukin-2 receptor monoclonal antibody induction with tacrolimus and mycophenolate mofetil combination maintenance, both regimens using steroid withdrawal after 7 days. METHODS: One hundred twenty-three live or deceased donor renal transplant recipients were randomized 2:1 to receive alemtuzumab/tacrolimus or daclizumab/tacrolimus/mycophenolate. The primary endpoint was survival with a functioning graft at 1 year. RESULTS: Both regimens produced equivalent, excellent outcomes with the primary outcome measure of 97.6% in the alemtuzumab arm and 95.1% in the daclizumab arm at 1 year (95% confidence interval of difference 6.9% to -1.7%) and at 2 years 92.6% and 95.1%. Rejection was less frequent in the alemtuzumab arm with 1- and 2-year rejection-free survival of 91.2% and 89.9% compared with 82.3% and 82.3% in the daclizumab arm. There were no significant differences in terms of the occurrence of opportunistic infections. CONCLUSION: Alemtuzumab induction with tacrolimus maintenance monotherapy and short-course steroid use provides a simple, safe, and effective immunosuppressive regimen for renal transplantation.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antineoplásicos/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Tacrolimus/uso terapéutico , Adulto , Alemtuzumab , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Antineoplásicos/efectos adversos , Daclizumab , Quimioterapia Combinada , Femenino , Supervivencia de Injerto/inmunología , Supervivencia de Injerto/fisiología , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/uso terapéutico , Inmunosupresores/efectos adversos , Trasplante de Riñón/fisiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Tacrolimus/efectos adversos , Resultado del Tratamiento
15.
Transplantation ; 92(2): 176-82, 2011 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-21637139

RESUMEN

BACKGROUND: Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied. METHODS: We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P = 0.0016, 0.001, and 0.012, respectively). RESULTS: Allograft survival was inferior in the AMR group (70.2%) compared with the nonrejector group (97.0%) (P<0.001). Forty-two of 48 (87.5%) of patients with acute AMR had DSAbs. Patients with CII DSAbs at the time of AMR, whether alone or in combination with CI DSAbs had the worst allograft survival (P = 0.014). Both the mean cumulative and immunodominant mean fluorescence index were higher in those patients who subsequently lost their grafts (P<0.001). Patients with diffuse C4d staining had inferior allograft survival than those with focal C4d or no staining (P = 0.02). There was no significant difference in survival by histological grade but a trend to inferior outcomes in those with vascular involvement (P = 0.06). Those patients who met the full Banff criteria had worse survival than those with suspicion for AMR only (P = 0.04). CONCLUSION: This study identifies patients at risk of graft failure from AMR. These patients may benefit from newer therapeutic strategies including the use of eculizumab or bortezomib.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Anticuerpos Antineoplásicos/efectos adversos , Anticuerpos/fisiología , Antígenos CD/inmunología , Antígenos de Neoplasias/inmunología , Glicoproteínas/inmunología , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Adulto , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Antígeno CD52 , Complemento C4b/metabolismo , Femenino , Rechazo de Injerto/diagnóstico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos
16.
Clin Transplant ; 25(3): E312-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21362049

RESUMEN

Development of live donor kidney transplantation (LDKT) programs has intensified debate regarding acceptability of certain donor categories and potential commercialization. Concerning these issues, we surveyed the views of medical and nursing staff caring for patients with renal failure and renal transplant recipients and donors. Participants were recruited from a tertiary transplant unit and invited to complete an anonymous questionnaire. Four hundred and sixty-four participants completed the questionnaire (42% response). One hundred and sixty-eight (36.2%) were health care professionals and 296 (63.8%) patients; 85.6% of participants were willing to donate to their children, 80.2% to siblings, 80.8% to parents, 72% to a non-blood-related relative or friend, and 15.3% to a stranger. If participants had hypothetical renal failure, they were prepared to accept a kidney from a parent (79.5%), sibling (78.7%), child (56.3%), a non-blood-related relative or friend (79.3%), or stranger (54.1%). Regarding commercialization, responders' attitudes were that the donor should not accept financial reward (29.1%), be compensated for expenses only (60.6%), or should receive a direct financial reward (10.1%). For non-directed donation, 23.5%, 55.6%, and 20.7% were not in support of reward, compensation only, and financial reward, respectively. While live kidney donation was accepted by the majority of individuals surveyed, only the minority approved of commercialization.


Asunto(s)
Actitud del Personal de Salud , Donación Directa de Tejido/ética , Trasplante de Riñón/economía , Trasplante de Riñón/ética , Donadores Vivos , Obtención de Tejidos y Órganos/economía , Obtención de Tejidos y Órganos/ética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Recolección de Datos , Donación Directa de Tejido/legislación & jurisprudencia , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven
17.
Eur J Immunol ; 40(11): 3280-90, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21061447

RESUMEN

The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8(+) /CD4(+) T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the "suspicious" form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.


Asunto(s)
Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Relación CD4-CD8 , Femenino , Estudios de Seguimiento , Rechazo de Injerto/sangre , Rechazo de Injerto/patología , Humanos , Terapia de Inmunosupresión/métodos , Trasplante de Riñón/patología , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/metabolismo , Linfocitos T/patología , Trasplante Homólogo
18.
J Clin Invest ; 120(6): 1848-61, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20501943

RESUMEN

Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to alpha-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell-related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients.


Asunto(s)
Biomarcadores/metabolismo , Tolerancia Inmunológica/inmunología , Inmunosupresores/inmunología , Trasplante de Riñón/inmunología , Humanos , Tolerancia Inmunológica/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Donantes de Tejidos
19.
Blood ; 114(14): 3052-5, 2009 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-19638623

RESUMEN

Neutropenia is a recognized adverse event in patients treated with the humanized anti-CD52 monoclonal antibody alemtuzumab. However, as it is widely believed that neutrophils do not express CD52, the etiology of alemtuzumab-associated neutropenia is unclear. We have found that neutrophils express both mRNA coding for CD52 and the protein itself on the cell surface. We confirmed cell-surface expression using 3 different anti-CD52 antibodies, and note that neutrophils express lower levels of CD52 than lymphocytes and eosinophils. Further, incubation of alemtuzumab with neutrophils results in dose-dependent, complement-mediated lysis in the presence of both heterologous and autologous complement. These data offer an explanation for the etiology of alemtuzumab-associated neutropenia. In a climate of increased use of alemtuzumab in leukemia and other disease states, as well as in transplantation, these data highlight the need for increased vigilance of emerging neutropenia in patients treated with alemtuzumab.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Antineoplásicos/farmacología , Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Antineoplásicos/farmacología , Proteínas del Sistema Complemento/metabolismo , Citotoxicidad Inmunológica/efectos de los fármacos , Glicoproteínas/metabolismo , Neutrófilos/metabolismo , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Apoptosis/efectos de los fármacos , Antígeno CD52 , Eosinófilos/metabolismo , Citometría de Flujo , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Exp Clin Transplant ; 7(1): 1-7, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19364304

RESUMEN

OBJECTIVES: The ongoing development of live donor kidney transplant has generated many ethical dilemmas. It is important to be aware of the attitudes of transplant professionals involved in this practice. MATERIALS AND METHODS: An anonymous and confidential questionnaire was sent to 236 members of the medical and nursing staff of the West London Renal and Transplant Centre, to assess their views on the ethics of the current practice of live donor kidney transplant. RESULTS: Of the 236 questionnaires, 108 (45.8%) were returned. Respondents considered live donor kidney transplant ethically acceptable between blood relatives (100%), nonblood relatives and friends (92.6%), and strangers (47.2%). Most respondents were willing to donate a kidney to a blood relative (92.6%) or a nonblood relative or friend (81.5%), and 12.0% were willing to donate to a stranger. Considering themselves as potential recipients if they had end-stage renal disease, most would accept a kidney from a blood relative (91.7%) or nonblood relative or friend (85.2%),while 44.5% would accept a kidney from a stranger. The highest number of respondents (43.5%) believed that the recipient should approach the potential donor. About one-third believed there should be no financial reward, not even compensation for expenses, for donors; 8% favored direct financial rewards for donors known to recipients, and 18% favored rewards for donors not known to recipients. Slightly more than half were in favor of accepting donors with mild to moderate medical problems. CONCLUSIONS: Live related and unrelated kidney donation are considered ethically acceptable procedures, and nondirected donation is gaining support among transplant professionals. A substantial minority favored direct financial rewards for donors, especially in the case of nondirected donation.


Asunto(s)
Actitud del Personal de Salud , Donación Directa de Tejido/ética , Conocimientos, Actitudes y Práctica en Salud , Trasplante de Riñón/ética , Donadores Vivos/ética , Obtención de Tejidos y Órganos/ética , Adolescente , Adulto , Anciano , Altruismo , Donación Directa de Tejido/legislación & jurisprudencia , Familia , Femenino , Donaciones , Humanos , Relaciones Interpersonales , Trasplante de Riñón/economía , Trasplante de Riñón/enfermería , Londres , Masculino , Persona de Mediana Edad , Motivación , Encuestas y Cuestionarios , Obtención de Tejidos y Órganos/economía , Adulto Joven
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