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1.
Pediatr Transplant ; 28(4): e14763, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38682750

RESUMEN

BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Trasplante de Órganos , Complicaciones Posoperatorias , Humanos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/virología , Infecciones por Virus de Epstein-Barr/epidemiología , Masculino , Estudios Prospectivos , Niño , Femenino , Estados Unidos/epidemiología , Preescolar , Adolescente , Lactante , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/virología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Herpesvirus Humano 4 , Adulto Joven
2.
Future Cardiol ; 20(2): 81-88, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38275185

RESUMEN

Introduction: Coronary artery disease has become a global pandemic and a major cause of death. The risk-factor calculation for coronary artery damage is an invasive procedure. Aim: To compare coronary computed tomography angiography (CCTA) with standard of care (SOC) to calculate need for revascularization, invasive coronary angiography as well as for myocardial infarction (MI) incidence and all-cause mortality. Methodology, results & conclusion: CCTA is significantly correlated with a reduction in MI episodes (RR = 0.752, 95% CI = 0.578-1.409; p < 0.033) and an increase in revascularizations (RR = 1.401, 95% CI = 1.315-1.492; p < 0.001) and invasive coronary angiography procedures (RR = 1.304, 95% CI = 1.208-1.409; p < 0.001). However, it was found that it did not affect all-cause mortality. On the contrary, standard care approaches were associated with greater rates of MI but lesser referrals for invasive coronary angiography and revascularization.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Humanos , Angiografía por Tomografía Computarizada , Nivel de Atención , Angiografía Coronaria/métodos , Tomografía Computarizada por Rayos X/métodos , Infarto del Miocardio/complicaciones
3.
J Clin Psychol Med Settings ; 31(1): 163-173, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37589865

RESUMEN

Few studies in pediatric solid organ transplantation have examined non-adherence to immunosuppressive medication over time and its associations with demographic factors and post-transplant outcomes including late acute rejection and hospitalizations. We examined longitudinal variation in patient Medication Level Variability Index (MLVI) adherence data from pediatric kidney, liver, and heart transplant recipients. Patient and administrative data from the United Network for Organ Sharing were linked with electronic health records and MLVI values for 332 patients. Multilevel mediation modeling indicated comparatively more variation in MLVI values between patients than within patients, longitudinally, over 10 years post transplant. MLVI values significantly predicted late acute rejection and hospitalization. MLVI partially mediated patient factors and post-transplant outcomes for patient age indicating adolescents may benefit most from intervention efforts. Results demonstrate the importance of longitudinal assessment of adherence and differences among patients. Efforts to promote medication adherence should be adapted to high-risk patients to increase likelihood of adherence.


Asunto(s)
Inmunosupresores , Trasplante de Hígado , Adolescente , Niño , Humanos , Inmunosupresores/efectos adversos , Cumplimiento de la Medicación , Demografía
4.
Ann Surg ; 279(1): 187-190, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37470170

RESUMEN

OBJECTIVE: Historically, the American Board of Surgery required surgeons to pass the qualifying examination (QE) before taking the certifying examination (CE). However, in the 2020-2021 academic year, with mitigating circumstances related to COVID-19, the ABS removed this sequencing requirement to facilitate the certification process for those candidates who were negatively impacted by a QE delivery failure. This decoupling of the traditional order of exam delivery has provided a natural comparator to the traditional route and an analysis of the impact of examination sequencing on candidate performance. METHODS: All candidates who applied for the canceled July 2020 QE were allowed to take the CE before passing the QE. The sample was then reduced to include only first-time candidates to ensure comparable groups for performance outcomes. Logistic regression was used to analyze the relationship between the order of taking the QE and the CE, controlling for other examination performance, international medical graduate status, and gender. RESULTS: Only first-time candidates who took both examinations were compared (n=947). Examination sequence was not a significant predictor of QE pass/fail outcomes, OR=0.54; 95% CI, 0.19-1.61, P =0.26. However, examination sequence was a significant predictor of CE pass/fail outcomes, OR=2.54; 95% CI, 1.46-4.68, P =0.002. CONCLUSIONS: This important study suggests that preparation for the QE increases the probability of passing the CE and provides evidence that knowledge may be foundational for clinical judgment. The ABS will consider these findings for examination sequencing moving forward.


Asunto(s)
Cirugía General , Internado y Residencia , Cirujanos , Estados Unidos , Humanos , Consejos de Especialidades , Evaluación Educacional , Certificación , Modelos Logísticos , Cirugía General/educación , Competencia Clínica
5.
Pediatr Transplant ; 28(1): e14627, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37850237

RESUMEN

INTRODUCTION: Organ procurement organizations (OPO) have started to employ transplant-trained surgeons dedicated to organ procurement with the aim to increase allograft utilization and enhance the use of procured organs. We investigated the effects of an OPO-employed surgeon on the procurement and utilization of organs from pediatric donors within the Southwestern Transplant Alliance OPO. METHODS: OPO data were obtained for all procurements that were performed between 2014 and 2019. The analysis was performed to see if the presence of an OPO donor surgeon impacted the utilization of pediatric livers. Donor and recipient demographic data were examined between allografts procured with the presence of an OPO surgeon (OPO-Present) and those without an OPO surgeon (OPO-Absent). A p-value of <.05 was considered significant. RESULTS: Of 149 pediatric procurements, 91 included an OPO-donor surgeon. In procurements with OPO-Present, donors were younger (8.2 vs. 11.2, p < .05) and had longer distances to travel to the recipient center (334 vs. 175 miles p < .05), but had comparable cold ischemic times. In terms of organ share type, more OPO-Present livers were shared nationally and there was no difference in discard rate between OPO-Present and OPO-Absent procurements. Finally, OPO-Present livers were more likely to be transplanted to pediatric recipients compared to OPO-Absent (47.3% vs. 24.1% p < .05). CONCLUSION: The presence of an OPO surgeon has impacted organ utilization, leading to increased transplantation of pediatric livers in pediatric recipients, and has expanded the geographical share of pediatric livers.


Asunto(s)
Cirujanos , Obtención de Tejidos y Órganos , Trasplantes , Humanos , Niño , Donantes de Tejidos , Hígado/cirugía
6.
Transplantation ; 108(4): 940-946, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37831642

RESUMEN

BACKGROUND: The social determinants of health contribute to adverse post-liver transplant outcomes. Identifying unmet social risks may enable transplant teams to improve long-term outcomes for at-risk children. However, providers may feel uncomfortable asking about household-level social risks in the posttransplant period because they might make their patients/families uncomfortable. METHODS: We conducted a mixed-methods analysis of caregiver participants (ie, parents/guardians of pediatric liver transplant recipients) in the Social and Contextual Impact on Children Undergoing Liver Transplantation study to assess their perceptions of provider-based social risk screening. Participants (N = 109) completed a 20-min social determinants of health questionnaire that included questions on the acceptability of being asked intimate social risk questions. A subset of participants (N = 37) engaged in an in-depth qualitative interview to share their perceptions of social risk screening. RESULTS: Of 109 participants across 9 US transplant centers, 60% reported financial strain and 30% reported at least 1 material economic hardship (eg, food insecurity, housing instability). Overall, 65% of respondents reported it very or somewhat appropriate and 25% reported being neutral to being screened for social risks in a liver transplant setting. In qualitative analyses, participants reported trust in the providers and a clear understanding of the intention of the screening as prerequisites for liver transplant teams to perform social risk screening. CONCLUSIONS: Only a small minority of caregivers found social risk screening unacceptable. Pediatric liver transplant programs should implement routine social risk screening and prioritize the patient and family voices when establishing a screening program to ensure successful implementation.


Asunto(s)
Cuidadores , Trasplante de Hígado , Humanos , Niño , Trasplante de Hígado/efectos adversos , Vivienda , Pobreza , Determinantes Sociales de la Salud
7.
Liver Int ; 43(10): 2198-2209, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37548078

RESUMEN

BACKGROUND: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. METHODS: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates. RESULTS: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2). CONCLUSION: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes.


Asunto(s)
Atresia Biliar , Colestasis , Trasplante de Hígado , Humanos , Niño , Estados Unidos/epidemiología , Trasplante de Hígado/efectos adversos , Donadores Vivos , Resultado del Tratamiento , Atresia Biliar/cirugía , Atresia Biliar/etiología , Factores de Riesgo , Estudios Retrospectivos , Colestasis/etiología , Supervivencia de Injerto
8.
Indian J Pediatr ; 90(12): 1254-1256, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37450249

RESUMEN

This ambispective, observational study evaluated the impact of the COVID-19 pandemic on managing children with Infantile epileptic spasms syndrome (IESS) and the feasibility of telemedicine-based management for IESS. Caregivers of children with IESS were telephonically interviewed using a structured questionnaire and various relevant indices were compared between the study population and a pre-pandemic cohort from the same center. There was a significant increase in diagnostic lag during the pandemic (p = 0.04). Adrenocorticotropic hormone was the first-line antiseizure medication of choice in both cohorts and the response to treatment was also similar. Telemedicine was utilized by around 80% of caregivers and satisfaction rates with telemedicine were high. However, caregivers continued to rate physical consultations higher in preference.


Asunto(s)
COVID-19 , Espasmos Infantiles , Telemedicina , Humanos , Niño , Lactante , COVID-19/epidemiología , Espasmos Infantiles/tratamiento farmacológico , Pandemias , Anticonvulsivantes/uso terapéutico , Síndrome , Espasmo/tratamiento farmacológico , Espasmo/epidemiología
9.
Paediatr Anaesth ; 33(9): 754-764, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37326251

RESUMEN

INTRODUCTION: Fluid administration is an important aspect of the management of children undergoing liver transplantation and may impact postoperative outcomes. Our aim was to evaluate the association between volume of intraoperative fluid administration and our primary outcome, the duration of postoperative mechanical ventilation following pediatric liver transplantation. Secondary outcomes included intensive care unit length of stay and hospital length of stay. METHODS: We conducted a multicenter, retrospective cohort study using electronic data from three major pediatric liver transplant centers. Intraoperative fluid administration was indexed to weight and duration of anesthesia. Univariate and stepwise linear regression analyses were conducted. RESULTS: Among 286 successful pediatric liver transplants, the median duration of postoperative mechanical ventilation was 10.8 h (IQR 0.0, 35.4), the median intensive care unit length of stay was 4.3 days (IQR 2.7, 6.8), and the median hospital length of stay was 13.6 days (9.8, 21.1). Univariate linear regression showed a weak correlation between intraoperative fluids and duration of ventilation (r2 = .037, p = .001). Following stepwise linear regression, intraoperative fluid administration remained weakly correlated (r2 = .161, p = .04) with duration of postoperative ventilation. The following variables were also independently correlated with duration of ventilation: center (Riley Children's Health versus Children's Health Dallas, p = .001), and open abdominal incision after transplant (p = .001). DISCUSSION: The amount of intraoperative fluid administration is correlated with duration of postoperative mechanical ventilation in children undergoing liver transplantation, however, it does not seem to be a strong factor. CONCLUSIONS: Other modifiable factors should be sought which may lead to improved postoperative outcomes in this highly vulnerable patient population.


Asunto(s)
Trasplante de Hígado , Humanos , Niño , Tiempo de Internación , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Respiración Artificial
11.
Artif Organs ; 47(7): 1184-1191, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36906889

RESUMEN

INTRODUCTION: Elderly patients (≥65 years old) are increasingly undergoing liver transplantation and are more likely to be removed from the waitlist. Normothermic machine perfusion (NMP) holds promise in expanding the number of livers available for transplant and improving outcomes for marginal donors and recipients. We aimed to determine the impact of NMP on outcomes in elderly recipients at our institution and nationally using the UNOS database. METHODS: The use of NMP on outcomes in elderly recipients was reviewed using both the UNOS/SRTR database (2016-2022) and institutional data (2018-2020). Characteristics and clinical outcomes were compared between the NMP and static cold (control) groups within both populations. RESULTS: Nationally, using the UNOS/SRTR database, we identified 165 elderly recipients from 28 centers who received a liver allograft undergoing NMP and 4270 that underwent traditional cold static storage. NMP donors were older (48.3 vs. 43.4 years, p < 0.01), had similar rates of steatosis (8.5% vs 8.5%, p = 0.58), were more likely to be from a DCD (41.8% vs 12.3%, p < 0.01), and had a higher donor risk index (DRI; 1.70 vs. 1.60, p < 0.02). NMP recipients had similar age but had a lower MELD score at transplant (17.9 vs. 20.7, p = 0.01). Despite increased marginality of the donor graft, NMP recipients had similar allograft survival and decreased length of stay, even after accounting for recipient characteristics including MELD. Institutional data showed that 10 elderly recipients underwent NMP and 68 underwent cold static storage. At our institution, NMP recipients had a similar length of stay, rates of complications, and readmissions. CONCLUSIONS: NMP may mitigate donor risk factors that are relative contraindications for transplantation in elderly liver recipients, increasing the donor pool. The application of NMP in older recipients should be considered.


Asunto(s)
Trasplante de Hígado , Preservación de Órganos , Humanos , Anciano , Receptores de Trasplantes , Perfusión , Hígado , Trasplante de Hígado/efectos adversos
13.
Am J Transplant ; 23(5): 611-618, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36796762

RESUMEN

Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at an increased risk of EBV-positive PTLD could influence clinical management of immunosuppression and other therapies, improving posttransplant outcomes. A 7-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at positions 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk of EBV-positive PTLD (clinical trials: NCT02182986). DNA was isolated from peripheral blood of EBV-positive PTLD case patients and matched controls (1:2 nested case:control), and the cytoplasmic tail of LMP1 was sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV-positive PTLD. DNA was sequenced from 32 PTLD case patients and 62 matched controls. Both LMP1 mutations were present in 31 of 32 PTLD cases (96.9%) and in 45 of 62 matched controls (72.6%) (P = .005; OR = 11.7; 95% confidence interval, 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk of development of EBV-positive PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV-positive PTLD.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Humanos , Niño , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Estudios Prospectivos , Trastornos Linfoproliferativos/etiología , Mutación , Proteínas de la Membrana
14.
Pediatr Transplant ; 27(2): e14432, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36369617

RESUMEN

BACKGROUND: Pediatric recipients of living donor kidneys have a low rate of delayed graft function (DGF). We examined the incidence, risk factors and outcomes of DGF in pediatric patients who received a living donor allograft. METHODS: The STARfile was queried to examine all pediatric patients transplanted with a living donor kidney between 2000 and 2020. Donor and recipient demographic data were examined, as were survival and outcomes. Recipients were stratified into DGF and no DGF groups. DGF was defined as the need for dialysis within the first week after transplant. RESULTS: 6480 pediatric patients received a living donor (LD) kidney transplant during the study period. 269 (4.2%) developed DGF post-transplant. Donors were similar in age, creatinine, and cold ischemia time. Recipients of kidneys with DGF were similar in age, sensitization status and HLA mismatch. Focal segmental glomerulosclerosis (FSGS) was the most common diagnosis in recipients with DGF, and allograft thrombosis was the most common cause of graft loss in this group. Small recipients (weight < 15 kg) were found to have a significantly higher rate of DGF. Length of stay doubled in recipients with DGF, and rejection rates were higher post-transplant. Recipients of LD kidneys who developed DGF had significantly worse 1 year allograft survival (67% vs. 98%, p < .0001). CONCLUSIONS: Pediatric living donor kidney transplant recipients who experience DGF have significantly poorer allograft survival. Optimizing the donor and recipient matching to avoid compounding risks may allow for better outcomes.


Asunto(s)
Trasplante de Riñón , Humanos , Niño , Trasplante de Riñón/efectos adversos , Donadores Vivos , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/etiología , Supervivencia de Injerto , Rechazo de Injerto/epidemiología , Riñón , Donantes de Tejidos , Factores de Riesgo
15.
Transplantation ; 107(3): 648-653, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36253907

RESUMEN

BACKGROUND: The recent trend of organ procurement organizations (OPOs) employing independent surgeons for organ procurement has been developed with the goal of improving the supply of suitable organs for transplantation. We investigated the effects that the addition of an OPO-employed, organ-procurement specialist has on liver allograft discard rate, marginal organ utilization, and graft survival. METHODS: Organ Procurement and Transplant Network and OPO data were retrospectively studied between April 1, 2014' and July 31, 2019' within the Southwest Transplant Alliance donor service area. Liver procurements with an OPO-surgeon present (OPO-Present) were compared to those without the involvement of an OPO surgeon (OPO-Absent). Donor and recipient characteristics as well as outcomes were analyzed across groups using propensity score matching. RESULTS: In total 869 OPO-Present liver allografts had similar rates of discard (5.2%) compared to 771 OPO-Absent livers (5.8%). However, after adjusting for donor risk, OPO-Present livers had a lower propensity of discard compared to OPO-Absent (3.4% versus 7.6%, P < 0.05). OPO-Present livers were more likely to be shared nationally (11.0% versus 4.8%, P < 0.001). Outcome analysis showed allograft survival of OPO-Present livers at 5 y was comparable to OPO-Absent livers (79.5% versus 80%, P = 0.34). CONCLUSIONS: The presence of an OPO surgeon was associated with decreased liver allograft discard and increased utilization of marginal donor organs. The OPO surgeon's presence represents a potential strategy to increase organ utilization nationally.


Asunto(s)
Cirujanos , Obtención de Tejidos y Órganos , Humanos , Estudios Retrospectivos , Donantes de Tejidos , Hígado , Aloinjertos
16.
Liver Transpl ; 2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-38166123

RESUMEN

Disparities exist in pediatric liver transplant (LT). We characterized barriers and facilitators to providing transplant and social care within pediatric LT clinics. This was a multicenter qualitative study. We oversampled caregivers reporting household financial strain, material economic hardship, or demonstrating poor health literacy. We also enrolled transplant team members. We conducted semistructured interviews with participants. Caregiver interviews focused on challenges addressing transplant and household needs. Transplant provider interviews focused on barriers and facilitators to providing social care within transplant teams. Interviews were recorded, transcribed, and coded according to the Capability, Opportunity, Motivation-Behavior model. We interviewed 27 caregivers and 27 transplant team members. Fifty-two percent of caregivers reported a household income <$60,000, and 62% reported financial resource strain. Caregivers reported experiencing (1) high financial burdens after LT, (2) added caregiving labor that compounds the financial burden, (3) dependency on their social network's generosity for financial and logistical support, and (4) additional support being limited to the perioperative period. Transplant providers reported (1) relying on the pretransplant psychosocial assessment for identifying social risks, (2) discomfort initiating social risk discussions in the post-transplant period, (3) reliance on social workers to address new social risks, and (4) social workers feeling overburdened by quantity and quality of the social work referrals. We identified barriers to providing effective social care in pediatric LT, primarily a lack of comfort in assessing and addressing new social risks in the post-transplant period. Addressing these barriers should enhance social care delivery and improve outcomes for these children.

17.
Front Immunol ; 13: 994552, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36304469

RESUMEN

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. In our previous studies EBV infection was demonstrated to markedly alter the expression of host B cell microRNA (miR). Specifically, miR-194 expression was uniquely suppressed in EBV+ B cell lines from PTLD patients and the 3'untranslated region of IL-10 was determined to be targeted by miR-194. Although EBV has been shown to regulate host miR expression in B cell lymphoma cell lines, the expression of miRs in the circulation of patients with EBV-associated PTLD has not been studied. The objective of this study was to determine if changes in miR expression are associated with EBV+ PTLD. In this study, we have shown that miR-194 is significantly decreased in EBV+PTLD tumors and that additional miRs, including miRs-17, 19 and 106a are also reduced in EBV+PTLD as compared to EBV-PTLD. We quantitated the levels of miRs-17, 19, 106a, 155, and 194 in the plasma and extracellular vesicles (EV; 50-70 nm as determined by nanoparticle tracking analysis) from pediatric recipients of solid organ transplants with EBV+ PTLD+ that were matched 1:2 with EBV+ PTLD- pediatric transplant recipients as part of the NIH-sponsored Clinical Trials in Organ Transplantation in Children, (CTOTC-06) study. Levels of miRs-17, 19, 106a, and 194 were reduced in the plasma and extracellular vesicles (EV) of EBV+ PTLD+ group compared to matched controls, with miRs-17 (p = 0.034; plasma), miRs-19 (p = 0.029; EV) and miR-106a (p = 0.007; plasma and EV) being significantly reduced. Similar levels of miR-155 were detected in the plasma and EV of all pediatric SOT recipients. Importantly, ~90% of the cell-free miR were contained within the EV supporting that EBV+ PTLD tumor miR are detected in the circulation and suggesting that EVs, containing miRs, may have the potential to target and regulate cells of the immune system. Further development of diagnostic, mechanistic and potential therapeutic uses of the miRs in PTLD is warranted.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , MicroARNs , Trasplante de Órganos , Niño , Humanos , Herpesvirus Humano 4/genética , Receptores de Trasplantes , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/diagnóstico , Trasplante de Órganos/efectos adversos , MicroARNs/genética
18.
Surgery ; 172(4): 1257-1262, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35871852

RESUMEN

BACKGROUND: Liver transplantation has increased in volume and provides substantial survival benefit. However, there remains a need for value-based assessment of this costly procedure. METHODS: Model for end stage liver disease era adult recipients were identified using United Network for Organ Sharing Standard Transplant Analysis file data (n = 75,988) and compared across time periods (period A: February 2002 to January 2007; B: February 2007 to January 2013; C: February 2013 to January 2019). Liver centers were divided into volume tertiles for each period (small, medium, large). Value for the index transplant episode was defined as percentage graft survival ≥1 year divided by mean posttransplant duration of stay. RESULTS: All centers increased value over time due to ubiquitous improvement in 1-year graft survival. However, large centers demonstrated the most significant value change (large +17% vs small +7.0%, P < .001) due to a -8.5% reduction in large centers duration of stay from period A to C, while small centers duration of stay remained unchanged (-0.1%). Large centers delivered higher value despite more complex care: older recipients (54.8 ± 10.3 vs 53.0 ± 11.4 years P < .001), fewer model for end stage liver disease exceptions (34.0% vs 38.2%, P < .001), higher rates of candidate portal vein thrombosis (10.1% vs 8.5%, P < .001) and prior abdominal surgery (43.4% vs 37.4%, P < .001), and more marginal donor utilization (donor risk index 1.45 ± 0.38 vs 1.36 ± 0.33, P < .001). Mahalanobis metric matching demonstrated that compared with small centers, large centers progressively shortened recipient duration of stay per transplant in each period (A: -0.36 days, P = .437; B: -2.14 days, P < .001; C: -2.49 days, P < .001). CONCLUSION: There is value in liver transplant volume. Adoption of value-based practices from large centers may allow optimization of health care delivery for this costly procedure.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Obtención de Tejidos y Órganos , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Supervivencia de Injerto , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Donantes de Tejidos , Estados Unidos/epidemiología
19.
Health Soc Work ; 47(3): 165-174, 2022 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-35771953

RESUMEN

This study examined associations between scores on the Adolescent Medication Barriers Scale (AMBS) and the Parent Medication Barriers Scale (PMBS), patient and family factors, and medication adherence outcomes. Patients and caregivers from a pediatric solid organ transplantation (SOT) program were recruited for participation. Pediatric SOT recipients ages 10 to 21 years were eligible for participation. Analyses included reliability analyses and regression modeling with posttransplant medication adherence measured by Medication Level Variability Index scores. Seventy-three patients and caregivers completed an AMBS or PMBS questionnaire. Patient-caregiver inter-rater reliability was poor to fair. Greater medication barriers were reported among younger and female patients and families with more children. AMBS scores predicted greater nonadherence, while the PMBS was not predictive of adherence. Results point to the difficulty of assessing barriers to medication adherence and the lack of agreement between adolescent patients and caregivers. AMBS scores were more closely aligned with medication nonadherence, whereas PMBS scores may have been more influenced by family social factors. Adolescent reports of medication barriers may offer multidisciplinary transplant teams greater clinical utility when addressing these challenges with patients. Transplant social workers and psychologists should engage adolescents and caregivers in efforts to address medication nonadherence.


Asunto(s)
Trasplante de Órganos , Receptores de Trasplantes , Adolescente , Adulto , Cuidadores , Niño , Femenino , Humanos , Cumplimiento de la Medicación , Reproducibilidad de los Resultados , Adulto Joven
20.
Pediatr Transplant ; 26(5): e14282, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35445521

RESUMEN

BACKGROUND: NMP provides a superior strategy for the assessment and preservation of marginal donor livers and has demonstrated increased utilization and enhances organ quality when used in adult liver transplantation. We aimed to evaluate the interest of incorporating the use of NMP in pediatric liver transplantation. METHODS: An anonymous online survey was distributed to pediatric transplant surgeons and hepatologists across the United States. Respondent demographic information, attitudes toward NMP in pediatric liver transplantation, and barriers to utilization were examined. RESULTS: Thirty-two providers (18 transplant surgeons and 14 hepatologists) completed the survey, yielding a response rate of 64%. Half (50%) of respondents indicated prior exposure to NMP. Overall, 96% of respondents believed there was benefit to using NMP in pediatric liver transplantation. DCD (68%) and post-cross-clamp (75%) grafts were the greatest opportunity for NMP use. A role in splitting livers ex vivo (71%) was also seen as a potential major opportunity. Cost was perceived as a barrier to implementation (36%), followed by institutional factors (32%). Cost tolerance was significantly greater in respondents residing in OPTN regions with greater than median wait times (63% vs. 11% in OPTN regions with greater vs. shorter wait times, p = .010). CONCLUSIONS: There is significant interest within the pediatric liver transplant community for NMP to expand the donor pool. Interest appears particularly strong in regions where wait times for suitable pediatric donors are prolonged.


Asunto(s)
Trasplante de Hígado , Adulto , Actitud , Niño , Humanos , Hígado , Preservación de Órganos , Perfusión , Encuestas y Cuestionarios
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