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1.
Am J Bot ; 111(3): e16299, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38419145

RESUMEN

PREMISE: Astragalus (Fabaceae), with more than 3000 species, represents a globally successful radiation of morphologically highly similar species predominant across the northern hemisphere. It has attracted attention from systematists and biogeographers, who have asked what factors might be behind the extraordinary diversity of this important arid-adapted clade and what sets it apart from close relatives with far less species richness. METHODS: Here, for the first time using extensive phylogenetic sampling, we asked whether (1) Astragalus is uniquely characterized by bursts of radiation or whether diversification instead is uniform and no different from closely related taxa. Then we tested whether the species diversity of Astragalus is attributable specifically to its predilection for (2) cold and arid habitats, (3) particular soils, or to (4) chromosome evolution. Finally, we tested (5) whether Astragalus originated in central Asia as proposed and (6) whether niche evolutionary shifts were subsequently associated with the colonization of other continents. RESULTS: Our results point to the importance of heterogeneity in the diversification of Astragalus, with upshifts associated with the earliest divergences but not strongly tied to any abiotic factor or biogeographic regionalization tested here. The only potential correlate with diversification we identified was chromosome number. Biogeographic shifts have a strong association with the abiotic environment and highlight the importance of central Asia as a biogeographic gateway. CONCLUSIONS: Our investigation shows the importance of phylogenetic and evolutionary studies of logistically challenging "mega-radiations." Our findings reject any simple key innovation behind high diversity and underline the often nuanced, multifactorial processes leading to species-rich clades.


Asunto(s)
Planta del Astrágalo , Ecosistema , Filogenia , Filogeografía , Evolución Biológica
2.
Am J Transplant ; 23(12): 1893-1907, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37579817

RESUMEN

The aim of this study (CTOTC-09) was to assess the impact of "preformed" (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.


Asunto(s)
Trasplante de Corazón , Isoanticuerpos , Humanos , Niño , Masculino , Femenino , Antígenos HLA , Donantes de Tejidos , Trasplante de Corazón/efectos adversos , Trasplante Homólogo , Suero Antilinfocítico , Supervivencia de Injerto , Rechazo de Injerto , Estudios Retrospectivos
3.
Transpl Int ; 35: 10226, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35185381

RESUMEN

Previous analyses in pediatric heart transplant (HT) recipients using weight or height have not found donor-recipient size-mismatch to be associated with post-transplant mortality. A recent study in 3,215 normal US children developed an equation for left ventricular (LV) mass using body surface area (BSA). We assessed whether donor-recipient size match using predicted LV mass (PLM) is associated with post-transplant in-hospital mortality or 1-year graft survival. We identified 4,717 children <18 yrs old who received primary HT in the US during 01/2000 to 03/2015 and divided them into five groups [10%, 10%, 60% (reference group), 10% and 10%, respectively] with increasing donor-recipient PLM ratio. In adjusted analysis, group 1 children (PLM ratio ≤.90) were at higher risk of post-transplant in-hospital mortality [Odds Ratio (OR) 1.55, 95% CI 1.04, 2.31]. This association of the most undersized donors with recipient in-hospital mortality was similar when donor-recipient weight ratio<.88 or BSA ratio<.92 (lowest decile) were used instead. There was no difference in 1-year graft survival among groups. Utilizing donors with donor-recipient PLM ratio ≤.90 is associated with higher risk of early post-transplant mortality in pediatric HT recipients. However, this metric is not superior to donor-recipient weight ratio or BSA ratio for assessing size match.


Asunto(s)
Trasplante de Corazón , Obtención de Tejidos y Órganos , Tamaño Corporal , Niño , Supervivencia de Injerto , Humanos , Tamaño de los Órganos , Estudios Retrospectivos , Donantes de Tejidos
4.
Pediatr Transplant ; 26(5): e14268, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35304794

RESUMEN

BACKGROUND: This study aimed to characterize features present at the time of diagnosis and describe outcomes in patients with post-transplant lymphoproliferative disorder (PTLD) following pediatric solid organ transplantation. METHODS: We performed a retrospective review of solid organ transplant patients who developed pathologically confirmed PTLD at our center from 2006 to 2016. RESULTS: Of 594 patients included in this study, 41(6.9%) were diagnosed with PTLD. Median age at transplant was 5.6(IQR 1.7-16.1) years. Proportion of PTLD cases by organ transplanted and median time (IQR) to disease onset were: heart 11/144(7.6%) at 13.6(8.5-55.6) months, lung 7/52(13.5%) at 9.1(4.9-35) months, kidney 8/255(3.1%) at 39.5(13.9-57.1) months, liver 12/125(9.6%) at 7.7(5.5-22) months, intestine 0/4(0%), and multi-visceral 3/14(21.4%) at 5.4(5.4-5.6) months. No significant correlation was seen between recipient EBV status at transplant and timing of development of PTLD. There were six early lesions, 15 polymorphic, 19 monomorphic, and one uncharacterizable PTLD. Following immunosuppression reduction, 30 patients received rituximab, and 14 required chemotherapy. At median 25(IQR 12-53) months follow-up from the onset of PTLD, eight patients died secondary to transplant related complications, three are alive with active disease, and 30 have no evidence of disease. CONCLUSION: PTLD is a significant complication following pediatric solid organ transplantation. EBV levels in conjunction with symptomatic presentation following transplant may assist in detection of PTLD. Most patients can achieve long-term disease-free survival through immunosuppression reduction, anti-CD20 treatment, and chemotherapy in refractory cases.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Trasplante de Órganos , Antígenos CD20 , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/epidemiología , Humanos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trasplante de Órganos/efectos adversos , Estudios Retrospectivos , Rituximab/uso terapéutico
5.
Sensors (Basel) ; 22(8)2022 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-35458866

RESUMEN

For analytical approach-based word recognition techniques, the task of segmenting the word into individual characters is a big challenge, specifically for cursive handwriting. For this, a holistic approach can be a better option, wherein the entire word is passed to an appropriate recognizer. Gurumukhi script is a complex script for which a holistic approach can be proposed for offline handwritten word recognition. In this paper, the authors propose a Convolutional Neural Network-based architecture for recognition of the Gurumukhi month names. The architecture is designed with five convolutional layers and three pooling layers. The authors also prepared a dataset of 24,000 images, each with a size of 50 × 50. The dataset was collected from 500 distinct writers of different age groups and professions. The proposed method achieved training and validation accuracies of about 97.03% and 99.50%, respectively for the proposed dataset.


Asunto(s)
Lenguaje , Redes Neurales de la Computación , Escritura Manual
6.
Pediatr Transplant ; 24(5): e13738, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32525246

RESUMEN

TDI is considered superior to conventional echocardiography for detecting changes in graft function during rejection in adults but has not demonstrated after pediatric OHT. We retrospectively analyzed echocardiograms performed within 24 hours of biopsy in 122 recipients with median age of 8.7 years. Using biopsy findings as the gold standard, we compared paired rejection and non-rejection echocardiograms using each patient as their own control. We included pairs of LV dimensions, FS, volumes, mass, mass/volume, sphericity, wall stress, SSI, SVI, and TDI velocities in this comparison. C-statistic was used to assess discrimination for individual echo variables and combinations of variables. Overall, 647 non-rejection and 24 rejection biopsy-echo pairs were identified. There was a significant decline in TDI velocities and their Z-scores during rejection but not in conventional variables (P ≤ .005). The variable that best discriminated rejection from non-rejection was LV S', with C-statistic = 0.93. Conventional echo variables performed less well with C-statistic range 0.65-0.67 for LV EF, shortening fraction, and mass. TDI is superior to conventional echocardiography measures for discriminating rejection from non-rejection. The use of newer non-invasive parameters to detect myocardial dysfunction and shifting the paradigm of rejection surveillance to detection of non-rejection together provide a promising approach to reducing the need for biopsy in pediatric heart recipients.


Asunto(s)
Ecocardiografía/métodos , Rechazo de Injerto/diagnóstico por imagen , Trasplante de Corazón , Adolescente , Biopsia , Niño , Preescolar , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Rechazo de Injerto/patología , Corazón/diagnóstico por imagen , Humanos , Lactante , Recién Nacido , Masculino , Miocardio/patología , Curva ROC , Estudios Retrospectivos , Adulto Joven
7.
Pediatr Transplant ; 23(7): e13543, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31313435

RESUMEN

LV E/E' ratio obtained using Doppler echocardiography is considered a surrogate for LV filling pressure in adults but has performed poorly in children. We hypothesized that LV E/E' ratio Z-score, adjusted for age, will relate more strongly to LV filling pressures than LV E/E' ratio in pediatric HT recipients. We analyzed 751 echocardiograms performed within 24 hours of a heart catheterization in 122 pediatric HT recipients (median age at HT 13 years, median 6 studies per patient). The primary end-point was PCWP, assessed both as a continuous and a binary variable. Associations with LV E/E' ratios and z-scores were assessed using generalized estimating equations models. PCWP, LV E/E' ratios (using E' from LV free wall, septum, and their average), and LV E/E' ratio Z-scores, all declined over time after HT. LV E/E' ratios and their Z-scores were significantly associated with PCWP assessed as a continuous variable (P < 0.001 for all); however, the relationship was weak (R2 range, 0.083 to 0.121). LV E/E' ratios and their Z-scores were also significantly associated with PCWP as a binary variable (P < 0.001 for all) but with only modest ability to discriminate PCWP ≥15 mm Hg (c-statistic range, 0.660 to 0.695). The association between LV E/E' ratio and PCWP in pediatric HT recipients is modest. Using a LV E/E' ratio Z-score did not result in significantly improved association with PCWP. Current Doppler echocardiographic methods are unreliable for estimating LV filling pressures in pediatric HT recipients.


Asunto(s)
Ecocardiografía Doppler , Trasplante de Corazón , Disfunción Ventricular Izquierda/fisiopatología , Adolescente , Adulto , Presión Sanguínea , Cateterismo Cardíaco , Niño , Preescolar , Femenino , Insuficiencia Cardíaca/cirugía , Humanos , Lactante , Masculino , Presión Esfenoidal Pulmonar , Estudios Retrospectivos , Disfunción Ventricular Izquierda/cirugía , Función Ventricular Izquierda , Adulto Joven
8.
Pediatr Transplant ; 23(4): e13414, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30973190

RESUMEN

Primary graft dysfunction following HTx is associated with significant morbidity and mortality. This study aimed to assess the incidence of, risk factors for, and outcomes of children requiring ECMO within 24 hours of HTx. This study utilized a linked PHIS/SRTR database of pediatric HTx recipients (2002-2016). Post-HTx ECMO was identified using inpatient billing data. Logistic regression assessed risk factors for post-HTx ECMO. Kaplan-Meier analyses assessed in-hospital mortality and post-discharge survival. A total of 2820 patients were included with 224 (7.9%) requiring ECMO. Independent risk factors for post-HTx ECMO include age <1 year (aOR: 2.2, 95% CI: 1.3-3.7, P = 0.006) or 1-5 years (aOR: 2.1, 95% CI: 1.3-3.4, P = 0.002), and ECMO support at HTx (aOR: 27.4, 95% CI: 15.2-49.6, P < 0.001). Survival to discharge decreased with increasing duration of post-HTx ECMO support; 89% for 1-3 days, 79.1% for 4-6 days, 63.2% for 7-9 days, and 18.8% for ≥10 days. There was no difference in long-term survival for patients requiring post-HTx ECMO who survived to hospital discharge (P = 0.434). There are identifiable risk factors associated with the need for ECMO in the post-HTx period. Length of time on ECMO post-HTx is strongly associated with the risk of in-hospital mortality. Patients who require ECMO early post-HTx and survive to discharge have comparable outcomes to patients who did not require ECMO.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/métodos , Adolescente , Niño , Preescolar , Femenino , Rechazo de Injerto/etiología , Supervivencia de Injerto , Trasplante de Corazón/mortalidad , Corazón Auxiliar , Humanos , Incidencia , Lactante , Estimación de Kaplan-Meier , Masculino , Disfunción Primaria del Injerto/etiología , Análisis de Regresión , Factores de Riesgo , Resultado del Tratamiento
9.
Pediatr Transplant ; 23(7): e13561, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31483086

RESUMEN

The frequency, indications, and outcomes for readmission following pediatric heart transplantation are poorly characterized. A better understanding of this phenomenon will help guide strategies to address the causes of readmission. Data from the Clinical Trials in Organ Transplantation for Children (CTOTC-04) multi-institutional collaborative study were utilized to determine incidence of, and risk factors for, hospital readmission within 30 days and 1 year from initial hospital discharge. Among 240 transplants at 8 centers, 227 subjects were discharged and had follow-up. 129 subjects (56.8%) were readmitted within one year; 71 had two or more readmissions. The 30-day and 1-year freedom from readmission were 70.5% (CI: 64.1%, 76.0%) and 42.2% (CI: 35.7%, 48.7%), respectively. The most common indications for readmissions were infection followed by rejection and fever without confirmed infection, accounting for 25.0%, 10.6%, and 6.2% of readmissions, respectively. Factors independently associated with increased risk of first readmission within 1 year (Cox proportional hazard model) were as follows: transplant in infancy (P = .05), longer transplant hospitalization (P = .04), lower UNOS urgency status (2/IB vs 1A) at transplant (P = .04), and Hispanic ethnicity (P = .05). Hospital readmission occurs frequently in the first year following discharge after heart transplantation with highest risk in the first 30 days. Infection is more common than rejection as cause for readmission, with death during readmission being rare. A number of patient factors are associated with higher risk of readmission. A fuller understanding of these risk factors may help tailor strategies to reduce unnecessary hospital readmission.


Asunto(s)
Trasplante de Corazón , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Estimación de Kaplan-Meier , Masculino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Modelos de Riesgos Proporcionales , Factores de Riesgo
10.
Am J Transplant ; 18(12): 2914-2923, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29806728

RESUMEN

The official analysis of posttransplant survival considers only recently transplanted patients and suggests absence of outcome differences among pediatric heart transplant (HT) centers. We sought to compare posttransplant survival among currently active pediatric HT centers in the United States over 15 years of activity. We identified all children <18 years old who underwent their first HT during 2000-2014 at US centers active during 2013-14. Recipients were followed until March 2016. A mixed-effects survival model with center as a random effect was used to assess center differences in patient and graft survival. Center case-mix and standardized mortality ratio (SMR) for 90-day mortality were assessed by applying an internally validated risk-model. Overall, 4271 children transplanted at 46 centers were analyzed. There was a significant center effect on risk-adjusted patient (P = .01) and graft survival (P < .001). Adjusting for 90-day SMR or center-volume, but not for case-mix, was associated with a significant reduction in center effect on long-term survival. There was no center effect on conditional survival in 90-day survivors. In conclusion, there are significant differences in posttransplant survival among pediatric HT centers in the United States. Centers with better short-term performance (lower SMR for 90-day mortality) maintain their outcome advantage on follow-up and have superior longer-term outcomes.


Asunto(s)
Rechazo de Injerto/mortalidad , Trasplante de Corazón/mortalidad , Mortalidad Hospitalaria/tendencias , Hospitales de Alto Volumen/estadística & datos numéricos , Complicaciones Posoperatorias , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/estadística & datos numéricos , Humanos , Lactante , Masculino , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Estados Unidos
11.
Pediatr Transplant ; 21(8)2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29105236

RESUMEN

The impact of liver parenchymal abnormalities on survival post-heart transplant remains unknown in pediatric Fontan patients. We assessed pediatric Fontan patients who underwent heart transplant and had documented pretransplant hepatic ultrasound (U/S) studies. Liver U/S findings were classified as normal (Group 1), mildly abnormal (Group 2, hepatomegaly/vascular congestion), or severely abnormal (Group 3, heterogeneous echotexture/nodularity). Among 30 study patients, 8 were classified as Group 1, 14 as Group 2, while 8 met Group 3 criteria. Pretransplant liver biochemistry and synthetic function were similar in all groups. Six Group 3 patients underwent liver biopsy; 4 demonstrated perisinusoidal or centrilobular fibrosis, and 2 had cirrhosis. Overall mortality was 30% (n = 9). Median follow-up was 5 years (range, 0.25-13 years). One-year survival was similar among all 3 groups (P = .37), with a trend toward higher cumulative 5-year survival in Group 1 (100%). The majority of pediatric Fontan patients who underwent heart transplant demonstrated abnormal preoperative liver ultrasound findings. Heterogeneous echotexture or nodularity detected on U/S frequently indicates underlying liver parenchymal abnormalities. The presence of severe liver abnormalities was not associated with higher early mortality post-heart transplant in pediatric Fontan patients; however, late outcomes must be further elucidated.


Asunto(s)
Anomalías Múltiples , Anomalías del Sistema Digestivo , Procedimiento de Fontan , Cardiopatías Congénitas/cirugía , Trasplante de Corazón/mortalidad , Hígado/anomalías , Anomalías Múltiples/diagnóstico por imagen , Adolescente , Adulto , Niño , Preescolar , Anomalías del Sistema Digestivo/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/mortalidad , Humanos , Hígado/diagnóstico por imagen , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía , Adulto Joven
12.
Circulation ; 131(10): 890-8, 2015 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-25587099

RESUMEN

BACKGROUND: Pediatric data on the impact of pre-heart transplantation (HTx) risk factors on early post-HTx outcomes remain inconclusive. Thus, among patients with previous congenital heart disease or cardiomyopathy, disease-specific risk models for graft loss were developed with the use pre-HTx recipient and donor characteristics. METHODS AND RESULTS: Patients enrolled in the Pediatric Heart Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis into cardiomyopathy and congenital heart disease cohorts. Logistic regression identified independent, pre-HTx risk factors. Risk models were constructed for 1-year post-HTx graft loss. Donor factors were added for model refinement. The models were validated with the use of patients transplanted from 2007 to 2009. Risk factors for graft loss were identified in patients with cardiomyopathy (n=896) and congenital heart disease (n=965). For cardiomyopathy, independent risk factors were earlier year of transplantation, nonwhite race, female sex, diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and panel reactive antibody >10%. The recipient characteristic risk model had good accuracy in the validation cohort, with predicted versus actual survival of 97.5% versus 95.3% (C statistic, 0.73). For patients with congenital heart disease, independent risk factors were nonwhite race, history of Fontan, ventilator dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower body surface area. The risk model was less accurate, with 86.6% predicted versus 92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor characteristics did not enhance model precision. CONCLUSIONS: Risk factors for 1-year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis. Modeling effectively stratifies the risk of graft loss in patients with cardiomyopathy and may be an adjunctive tool in allocation policies and center performance metrics.


Asunto(s)
Cardiomiopatías/cirugía , Rechazo de Injerto/epidemiología , Cardiopatías Congénitas/cirugía , Trasplante de Corazón , Modelos Estadísticos , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
13.
Int Ophthalmol ; 35(2): 159-65, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24958188

RESUMEN

To assess utility of PCR in the diagnosis of bacterial corneal ulcer and to compare sensitivity and specificity of this technique with conventional laboratory methods. A prospective nonrandomized investigative study conducted on 122 eyes of presumed bacterial keratitis. Samples were collected for bacterial and fungal culture and Gram stain smear. A separate sample was taken for PCR with 26 gauge needle and was dipped directly into Eppendorff tube with lysis buffer in it. Diagnosis of culture proven bacterial keratitis was established in 53 (43.4 %) and most common bacterial isolate was staphylococcal sp. (83 %). Direct microscopic examination of Gram stained smear revealed presence of bacteria in 24 (23.9 %) specimens and PCR positivity was evident in 56 (45.5 %). In preantibiotic treated eyes culture was positive in 15 (30 %), Gram stain in 9 (18 %), and PCR in 18 (36 %). The same for untreated (fresh) eyes, positivity of culture as well as PCR was noted in 38 (52.7 %) and that of Gram stain was noted in 20 (27.7 %). Sensitivity of Gram stain and PCR was 45.28 and 88.68 % respectively; whereas specificity was 92.75 % for Gram stain and 86.96 % for PCR. The average time taken for PCR reaction was 4-8 h while culture reporting took at least 24-48 h. Our findings suggest that PCR is a good adjunct modality to the "Gold Standard" technique in the diagnosis of bacterial corneal ulcer.


Asunto(s)
Técnicas Bacteriológicas/normas , Úlcera de la Córnea/diagnóstico , Infecciones Bacterianas del Ojo/diagnóstico , Reacción en Cadena de la Polimerasa/normas , Adolescente , Adulto , Distribución por Edad , Anciano , Bacterias/aislamiento & purificación , Técnicas Bacteriológicas/métodos , Niño , Úlcera de la Córnea/microbiología , Femenino , Violeta de Genciana/normas , Humanos , Masculino , Persona de Mediana Edad , Fenazinas/normas , Reacción en Cadena de la Polimerasa/métodos , Estudios Prospectivos , ARN Ribosómico 16S/análisis , Sensibilidad y Especificidad , Adulto Joven
14.
Transplantation ; 108(1): e8-e14, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37788365

RESUMEN

BACKGROUND: Short-term outcomes using steroid avoidance immune suppression are encouraging in pediatric heart transplant (HT) recipients at low risk of antibody-mediated rejection. We assessed medium-term outcomes in pediatric HT recipients initiated on a steroid avoidance protocol at our institution using surveillance biopsies. METHODS: All primary HT recipients during 2006-2020 who did not have a donor-specific antibody were eligible for immune suppression consisting of 5-d Thymoglobulin/steroid induction followed by a tacrolimus-based, steroid-free regimen. We assessed freedom from graft failure (death or retransplant), acute rejection, posttransplant lymphoproliferative disease, and cardiac allograft vasculopathy. RESULTS: Overall, 150 of 181 primary HT recipients were eligible for steroid avoidance regimen. Their median age was 8.7 y, 41% had congenital heart disease, 23% were sensitized, and 35% were on a mechanical support. The median follow-up was 6.1 y. Eleven patients (8%) were on maintenance steroids at discharge and 13% at 1 y. Graft survival was 94% at 1 y and 87% at 5 y. Freedom from rejection was 73% at 1 y and 64% at 5 y. Freedom from posttransplant lymphoproliferative disease was 96% at 1 y and 95% at 5 y. Freedom from moderate cardiac allograft vasculopathy was 94% at 5 y. Eight patients developed diabetes. Estimated glomerular filtration rate was <60 mL/min/1.73 m 2 in 5% of the cohort at 5 y. CONCLUSIONS: Pediatric HT recipients at low risk of antibody-mediated rejection have excellent medium-term survival and relatively low incidence of posttransplant morbidities when managed using a steroid avoidance immune suppression protocol.


Asunto(s)
Trasplante de Corazón , Inmunosupresores , Humanos , Niño , Inmunosupresores/efectos adversos , Terapia de Inmunosupresión/métodos , Esteroides , Tacrolimus/efectos adversos , Anticuerpos , Trasplante de Corazón/efectos adversos , Rechazo de Injerto , Supervivencia de Injerto
15.
World J Pediatr Congenit Heart Surg ; 15(2): 215-223, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38404131

RESUMEN

BACKGROUND: Newborns with hypoplastic left heart syndrome (HLHS) who are considered at increased risk for death following Norwood/Sano surgery often undergo hybrid palliation (HP) as initial surgery. We aimed to compile the HP experience in HLHS and its variants and assess the rates of, and risk factors for, death and heart transplantation. METHODS: CINAHL, CINAHL PLUS, PubMed/MEDLINE, and SCOPUS were systematically searched for HP outcome studies of death or heart transplantation in HLHS between 1998 and 2022. Pooled incidence was estimated, and potential risk factors were identified using random-effects meta-analysis and reconstructed time-to-event data from Kaplan-Meier curves. RESULTS: Thirty-three publications were included in our review. Overall, of 1,162 patients 417 died and 57 underwent heart transplantation, resulting in a combined outcome of 40.7%, (474/1,162). There was a trend toward decreasing mortality risk across the stages of palliation. Pooled mortality between HP and comprehensive stage 2 palliation was 25%, after stage 2 up to Fontan palliation was 16%, and 6% post-Fontan. The incidence of death or heart transplantation was higher in high-risk patients-43% died and 10% received heart transplantation. CONCLUSION: Our systematic review and meta-analysis found high rates of death or heart transplantation in HP of HLHS patients between HP and Fontan surgeries. All patients should be closely followed during the initial interstage period, which is associated with the highest hazard. Prospective studies on appropriate patient selection, indications, and / or alternatives, as well as refining HP strategies for managing newborns with HLHS are needed to improve outcomes.


Asunto(s)
Procedimiento de Fontan , Trasplante de Corazón , Síndrome del Corazón Izquierdo Hipoplásico , Procedimientos de Norwood , Humanos , Recién Nacido , Lactante , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Procedimientos de Norwood/métodos , Cuidados Paliativos/métodos , Resultado del Tratamiento
16.
J Heart Lung Transplant ; 43(6): 963-972, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38423415

RESUMEN

BACKGROUND: Pediatric heart transplant (HT) candidates experience high waitlist mortality due to a limited donor pool that is constrained in part by anti-HLA sensitization. We evaluated the impact of CDC and Flow donor-specific crossmatch (XM) results on pediatric HT outcomes. METHODS: All pediatric HTs between 1999 and 2019 in the OPTN database were included. Donor-specific XM results were sub-categorized based on CDC and Flow results. Primary outcomes were treated rejection in the first year and time to death or allograft loss. Propensity scores were utilized to adjust for differences in baseline characteristics. RESULTS: A total of 4,695 pediatric HT patients with T-cell XM data were included. After propensity score adjustment, a positive T-cell CDC-XM was associated with 2 times higher odds of treated rejection (OR 2.29 (1.56, 3.37)) and shorter time to death/allograft loss (HR 1.50 (1.19, 1.88)) compared to a negative Flow-XM. HT recipients who were Flow-XM positive with negative/unknown CDC-XM did not have higher odds of rejection or shorter time to death/allograft loss. An isolated positive B-cell XM was also not associated with worse outcomes. Over the study period XM testing shifted from CDC- to Flow-based assays. CONCLUSIONS: A positive donor-specific T-cell CDC-XM was associated with rejection and death/allograft loss following pediatric HT. This association was not observed with a positive T-cell Flow-XM or B-cell XM result alone. The shift away from performing the CDC-XM may result in loss of important prognostic information unless the clinical relevance of quantitative Flow-XM results on heart transplant outcomes is systematically studied.


Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Corazón , Humanos , Niño , Masculino , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/epidemiología , Preescolar , Estudios Retrospectivos , Prueba de Histocompatibilidad , Adolescente , Lactante , Donantes de Tejidos
17.
Circulation ; 125(24): 3022-30, 2012 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-22589383

RESUMEN

BACKGROUND: Racial differences in long-term survival after heart transplant (HT) are well known. We sought to assess racial/ethnic differences in wait-list outcomes among patients listed for HT in the United States in the current era. METHODS AND RESULTS: We compared wait-list and posttransplant in-hospital mortality among white, black, and Hispanic patients ≥ 18 years of age listed for their primary HT in the United States between July 2006 and September 2010. Of 10 377 patients analyzed, 71% were white, 21% were black, and 8% were Hispanic. Black and Hispanic patients were more likely to be listed with higher urgency (listing status 1A/1B) in comparison with white patients (P<0.001). Overall, 10.5% of white, 11.6% of black, and 13.4% of Hispanic candidates died on the wait-list or became too sick for a transplant within 1 year of listing. After adjusting for baseline risk factors, Hispanic patients were at higher risk of wait-list mortality (hazard ratio 1.51, 95% CI 1.23, 1.85) in comparison with white patients, but not black patients (hazard ratio 1.13, 95% CI 0.97, 1.31). In comparison with white HT recipients, posttransplant in-hospital mortality was higher in black recipients (odds ratio 1.53, 95% CI 1.15, 2.03) but was not different in Hispanic recipients (odds ratio 0.78, 95% CI 0.48, 1.29). CONCLUSIONS: Hispanic patients listed for HT in the United States appear to be at higher risk of dying on the wait-list or becoming too sick for a transplant in comparison with white patients. Black patients are not at higher risk of wait-list mortality, but they have higher early posttransplant mortality.


Asunto(s)
Trasplante de Corazón/etnología , Trasplante de Corazón/mortalidad , Listas de Espera , Adulto , Anciano , Población Negra , Femenino , Hispánicos o Latinos , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , Población Blanca
20.
Pediatr Transplant ; 17(7): 661-9, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23919762

RESUMEN

Sensitization to HLA is a risk factor for adverse outcomes after heart transplantation. Requiring a negative prospective CM results in longer waiting times and increased waitlist mortality. We report outcomes in a cohort of sensitized children who underwent transplant despite a positive CDC CM+ using a protocol of antibody depletion at time of transplant, followed by serial IVIG administration. All patients <21 yrs old who underwent heart transplantation at Boston Children's Hospital from 1/1998 to 1/2011 were included. We compared freedom from allograft loss, allograft rejection, and serious infection between CM+ and CM- recipients. Of 134 patients in the cohort, 33 (25%) were sensitized prior to transplantation and 12 (9%) received a CM+ heart transplant. Serious infection in the first post-transplant year was more prevalent in the CM+ patients compared with CM- patients (50% vs. 16%; p = 0.005), as was HD-AMR (50% vs. 2%; p < 0.001). There was no difference in freedom from allograft loss or any rejection. At our center, children transplanted despite a positive CM had acceptable allograft survival and risk of any rejection, but a higher risk of HD-AMR and serious infection.


Asunto(s)
Anticuerpos/inmunología , Pruebas Inmunológicas de Citotoxicidad , Rechazo de Injerto/inmunología , Trasplante de Corazón/métodos , Adolescente , Niño , Preescolar , Femenino , Supervivencia de Injerto , Antígenos HLA/inmunología , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/cirugía , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunosupresores/uso terapéutico , Lactante , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
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