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1.
Am J Transplant ; 18(9): 2148-2162, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29673058

RESUMEN

Sensitization is common in pediatric heart transplant candidates and waitlist mortality is high. Transplantation across a positive crossmatch may reduce wait time, but is considered high risk. We prospectively recruited consecutive candidates at eight North American centers. At transplantation, subjects were categorized as nonsensitized or sensitized (presence of ≥1 HLA antibody with MFI ≥1000 using single antigen beads). Sensitized subjects were further classified as complement-dependent cytotoxicity crossmatch (CDC-crossmatch) positive or negative and as donor-specific antibodies (DSA) positive or negative. Immunosuppression was standardized. CDC-crossmatch-positive subjects also received perioperative antibody removal, maintenance corticosteroids, and intravenous immunoglobulin. The primary endpoint was the 1 year incidence rate of a composite of death, retransplantation, or rejection with hemodynamic compromise. 317 subjects were screened, 290 enrolled and 240 transplanted (51 with pretransplant DSA, 11 with positive CDC-crossmatch). The incidence rates of the primary endpoint did not differ statistically between groups; nonsensitized 6.7% (CI: 2.7%, 13.3%), sensitized crossmatch positive 18.2% (CI: 2.3%, 51.8%), sensitized crossmatch negative 10.7% (CI: 5.7%, 18.0%), P = .2354. The primary endpoint also did not differ by DSA status. Freedom from antibody-mediated and cellular rejection was lower in the crossmatch positive group and/or in the presence of DSA. Follow-up will determine if acceptable outcomes can be achieved long-term.


Asunto(s)
Tipificación y Pruebas Cruzadas Sanguíneas/mortalidad , Rechazo de Injerto/mortalidad , Antígenos HLA/inmunología , Trasplante de Corazón/efectos adversos , Isoanticuerpos/inmunología , Complicaciones Posoperatorias , Donantes de Tejidos , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Prueba de Histocompatibilidad , Humanos , Terapia de Inmunosupresión , Lactante , Isoanticuerpos/sangre , Masculino , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia
2.
Am J Transplant ; 18(9): 2163-2174, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29442424

RESUMEN

Data on the clinical importance of newly detected donor-specific anti-HLA antibodies (ndDSAs) after pediatric heart transplantation are lacking despite mounting evidence of the detrimental effect of de novo DSAs in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSAs in the first year posttransplantation to determine their incidence, pattern, and clinical impact. One-third of patients developed ndDSAs; when present, these were mostly detected within the first 6 weeks after transplantation, suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of preexisting DSAs, patients with ndDSAs had significantly more acute cellular rejection but not antibody-mediated rejection, and there was no impact on graft and patient survival in the first year posttransplantation. Risk factors for ndDSAs included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year after pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pretransplantation antibody screen. The impact on late graft and patient outcomes of first-year ndDSAs is being assessed in an extended cohort of patients.


Asunto(s)
Rechazo de Injerto/mortalidad , Supervivencia de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Corazón/efectos adversos , Isoanticuerpos/efectos adversos , Complicaciones Posoperatorias , Donantes de Tejidos , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Prueba de Histocompatibilidad , Humanos , Incidencia , Lactante , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Masculino , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto Joven
3.
Am J Transplant ; 17(10): 2712-2719, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28556519

RESUMEN

The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials.


Asunto(s)
Abatacept/uso terapéutico , Corticoesteroides/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Adolescente , Adulto , Anciano , Femenino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
4.
Am J Transplant ; 17(10): 2627-2639, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28371372

RESUMEN

We previously reported that two B cell receptor genes, IGKV1D-13 and IGKV4-1, were associated with tolerance following kidney transplantation. To assess the potential utility of this "signature," we conducted a prospective, multicenter study to determine the frequency of patients predicted tolerant within a cohort of patients deemed to be candidates for immunosuppressive minimization. At any single time point, 25-30% of patients were predicted to be tolerant, while 13.7% consistently displayed the tolerance "signature" over the 2-year study. We also examined the relationship of the presence of the tolerance "signature" on drug use and graft function. Contrary to expectations, the frequency of predicted tolerance was increased in patients receiving tacrolimus and reduced in those receiving corticosteroids, mycophenolate mofetil, or Thymoglobulin as induction. Surprisingly, patients consistently predicted to be tolerant displayed a statistically and clinically significant improvement in estimated glomerular filtration rate that increased over time following transplantation. These findings indicate that the frequency of patients consistently predicted to be tolerant is sufficiently high to be clinically relevant and confirm recent findings by others that immunosuppressive agents impact putative biomarkers of tolerance. The association of a B cell-based "signature" with graft function suggests that B cells may contribute to the function/survival of transplanted kidneys.


Asunto(s)
Tolerancia Inmunológica/genética , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Receptores de Antígenos de Linfocitos B/genética , Secuencia de Bases , Estudios de Cohortes , Cartilla de ADN , Humanos , Persona de Mediana Edad , Estudios Prospectivos
5.
Am J Transplant ; 16(1): 121-36, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26260101

RESUMEN

Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.


Asunto(s)
Biomarcadores/metabolismo , Enfermedad de la Arteria Coronaria/diagnóstico , Rechazo de Injerto/diagnóstico , Cardiopatías/cirugía , Trasplante de Corazón/efectos adversos , Adulto , Western Blotting , Estudios de Casos y Controles , Ensayos Clínicos como Asunto , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/metabolismo , Endotelina-1/metabolismo , Femenino , Perfilación de la Expresión Génica , Rechazo de Injerto/etiología , Rechazo de Injerto/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor A de Crecimiento Endotelial Vascular
6.
Am J Transplant ; 10(1): 81-8, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19663893

RESUMEN

In an effort to reduce rejection, extend allograft survival and minimize complications, we hypothesized that robust immunosuppression during the first 6 months after transplantation would allow for the safe withdrawal of steroids. A total of 274 pediatric subjects were enrolled and received an anti-CD25 antibody, sirolimus, calcineurin inhibitor and steroids. At 6 months after transplantation, subjects were randomized to steroid withdrawal (n=73) versus continued low-dose steroids (n=59). This study was stopped prior to target enrollment because of the incidence of post-transplant lymphoproliferative disorder. At the time of study termination, 132 subjects had been randomized and were available for analysis. At 18 months after transplantation, there was no difference in the standardized height z score; however, the standardized height velocity was greater in the steroid withdrawal group compared to the control group (p=0.033). There were no differences in acute rejection episodes between treatment groups. The 3-year allograft survival rate was 84.5% in the control group and 98.6% in the steroid withdrawal group (p=0.002). The immunosuppressive protocol utilized in this study allowed for the withdrawal of steroids without an increased risk of rejection or allograft loss. However, the complications associated with the use of this immunosuppressive protocol were too high to recommend its routine use in pediatric patients.


Asunto(s)
Corticoesteroides/administración & dosificación , Inmunosupresores/administración & dosificación , Trasplante de Riñón/métodos , Enfermedad Aguda , Adolescente , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Estatura/efectos de los fármacos , Niño , Preescolar , Método Doble Ciego , Femenino , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Lactante , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/fisiología , Trastornos Linfoproliferativos/etiología , Masculino , Medición de Riesgo , Factores de Tiempo , Adulto Joven
7.
Anaesthesia ; 55(7): 701-2, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10919440
8.
Adv Wound Care ; 12(9): 459-67, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10687558

RESUMEN

OBJECTIVE: This survey was conducted to assess the presence of skin ulcers within a home health agency population in the United States. DESIGN: This voluntary survey was conducted by 177 home health agencies. A single observation of each patient within the agency's active caseload formed the cohort examined. Patients deemed to be at low risk (Braden Scale score > 19) were eliminated from further evaluation, while those with skin ulcers were evaluated for wound- and caregiver-related factors. Surveys were conducted between March 1, 1996, and December 31, 1997. SETTING: Home health agencies in 19 states throughout the United States, with no restrictions on the type or acuity of the patients served. RESULTS: A total of 21,529 patients were surveyed, with a prevalence of pressure ulcers (inclusive of all stages) of 6.8% (n = 1455). Rates for each agency ranged between 0.5% and 35.7%. The total number of ulcers reported was 2526 (average per patient was 1.7), with 36% (n = 919) found on the sacrum and the buttocks. CONCLUSION: Pressure ulcers were the most frequently reported reason for admission to the agency's caseload. Survey results are similar to rates reported in other segments of the health care industry. However, among the home health care population, the primary caregiver is unlikely to be a health care professional. This survey found that the patient's spouse was the primary caregiver in 30% (n = 437) of the 1450 responses received regarding the relationship of the primary caregiver to the patient.


Asunto(s)
Agencias de Atención a Domicilio , Úlcera por Presión/epidemiología , Vendajes , Enfermería en Salud Comunitaria/métodos , Femenino , Humanos , Masculino , Evaluación en Enfermería , Vigilancia de la Población , Úlcera por Presión/clasificación , Úlcera por Presión/etiología , Úlcera por Presión/enfermería , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Cuidados de la Piel/métodos , Cuidados de la Piel/enfermería , Estados Unidos/epidemiología , Carga de Trabajo
10.
Ann Pharmacother ; 29(1): 57-65, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7711347

RESUMEN

OBJECTIVE: To review the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of hantavirus infections, focusing on the recent outbreak of hantavirus pulmonary syndrome in the US. DATA SOURCES: A MEDLINE search (1966 to present) of English language literature pertaining to hantaviruses was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: Hemorrhagic fever with renal syndrome (HFRS) has long been recognized in Eurasia and is the predominant disease manifestation of hantavirus infection worldwide. Hantavirus pulmonary syndrome (HPS) recently has been described in the US and exhibits greater pulmonary involvement and mortality than HFRS. Historically, 4 hantavirus serotypes (Hantaan, Seoul, Puumala, Prospect Hill) are recognized; however, additional serotypes have been proposed as distinct serogroups, including the serotype responsible for HPS in the Four Corners area: the Four Corners virus (FCV). Phylogenetic analysis shows that FCV is most closely related to Prospect Hill virus, another hantavirus previously isolated in the US that has not yet been identified with human disease. Additional hantavirus serotypes isolated in the US may provide insight into the prevalence of hantavirus infection and disease in this country. Inhalation of aerosolized virus is the predominant mechanism of hantavirus infection. Diagnosis is based primarily on clinical findings and serologic evidence of hantavirus antibody or direct evidence in clinical tissue specimens. Limited clinical studies evaluating ribavirin as a therapeutic modality demonstrated that the agent improves clinical outcome in HFRS. However, the role of ribavirin in the treatment of HPS remains to be determined. CONCLUSIONS: Hantavirus infections are becoming increasingly recognized as a cause of disease worldwide. Recognition of hantavirus disease in the US suggests enzoonosis of pathogenic hantaviruses. In the absence of a well-established cure, early diagnosis is imperative so that aggressive supportive care can be initiated.


Asunto(s)
Brotes de Enfermedades , Síndrome Pulmonar por Hantavirus/epidemiología , Arizona/epidemiología , Colorado/epidemiología , Orthohantavirus/clasificación , Síndrome Pulmonar por Hantavirus/diagnóstico , Síndrome Pulmonar por Hantavirus/virología , Humanos , New Mexico/epidemiología , Prevalencia , Factores de Tiempo , Utah/epidemiología
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