Infección asociada al nuevo Coronavirus (COVID-191 ) [Spanish]
Measurement of health-related quality of life in pediatric organ transplantation recipients: a systematic review of the PedsQL transplant module
DE: Organización Nacional de Trasplantes. A: Coordinadores Autonómicos de Trasplante; Coordinaciones Hospitalarias de trasplante; Equipos de Trasplante; Equipos de TPH; Grupo de Biovigilancia; Establecimientos de tejidos; CCAES. https://www.transplantevidence.com/docs/covid/ES200327_infection.pdf
Quality of Life Research. 2020;[record in progress]
OBJECTIVE To collect and assess the extant empirical literature assessing disease-specific health-related quality of life (HRQOL) in pediatric transplant recipients using the PedsQL 3.0 Transplant Module (PedsQL-TM) assessment. STUDY DESIGN A systematic search and review procedure was conducted of research reporting use and results of the PedsQL-TM with samples of pediatric heart, liver, kidney, and lung transplantation. Searches were conducted in nine scholarly databases and two additional sources to identify unpublished research. Multiple reviewers screened studies meeting inclusion criteria in accordance with PRISMA guidelines. RESULTS A final sample of nine studies reported findings for the PedsQL-TM with pediatric organ transplant recipients. Most studies relied on either kidney or liver transplant recipients from single pediatric transplant centers. Factor validity of the PedsQL-TM and inter-rater reliability (IRR) between patients and parents have not been adequately determined. Internal consistency reliability was found as acceptable or excellent across multiple studies. PedsQL-TM scores were found to vary with other HRQOL issues, yet few studies examined their association with medication adherence or posttransplant health outcomes. CONCLUSIONS With the goal of enhancing and sustaining HRQOL in pediatric organ transplant recipients, the need for a psychometrically valid and reliable measure of transplant-specific HRQOL is apparent. Research on the PedsQL-TM supports the promise of this measure although future efforts should be taken to examine measurement issues such as factor validity and IRR. Assessing transplant-specific HRQOL in these patients is paramount for their care and appropriate decision-making by patients, families, and the transplant team.
Information for transplant programs and OPOs regarding 2019 Novel Coronavirus
Guidance on the management of transplant recipients diagnosed with or suspected of having COVID19
The recent outbreak of a novel coronavirus (2019-nCoV) in Wuhan, Hubei Province, China and the finding of infection in many other countries including the United States has led to questions among transplant programs, Organ Procurement Organizations (OPOs) and patients. The Organ Procurement and Transplantation Network (OPTN) strives to provide up-to-date information to answer these questions and to provide guidance as needed. Accordingly, the OPTN Ad Hoc Donor Transmission Advisory Committee (DTAC), American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS), after careful review of information available from the Centers for Disease Control and Prevention (CDC), offers information to transplant programs and OPOs in light of these concerns. https://optn.transplant.hrsa.gov/news/information-for-transplant-programs-and-opos-regarding-2019-novel-coronavirus/
COVID-19: Clinical advice
This is a consensus opinion of a group of transplant professionals. The guidance is based on the sparse information available on transplant recipients in the literature and should be used in conjunction with local or national guidance. We understand that individual patients may need a bespoke plan but this is a general guideline which may help others when managing transplant recipients with, or suspected of having, COVID 19. All unwell transplant recipients should be discussed with their usual unit. This guidance does not cover cardiothoracic or small bowel transplant recipients. At the time of writing, there are no randomised controlled trials of additional therapy that show any benefit above standard supportive care. https://bts.org.uk/wp-content/uploads/2020/03/Clinical_management_transplant_recipients.pdf
18F-fluorodeoxyglucose use after cardiac transplant: A comparative study of suppression of physiological myocardial uptake
The general guidance is provided for clinical staff involved in facilitating organ donation in the UK. It provides links to COVID-19 Bulletins that are regularly published, guidance documents for deceased and living donation, and COVID-19 reporting forms. https://www.odt.nhs.uk/deceased-donation/covid-19-advice-for-clinicians/
Journal of Nuclear Cardiology. 2020;27(1):173-181
BACKGROUND 18F-fluorodeoxyglucose (FDG) has been useful in the evaluation of myocardial inflammatory processes. However, it is challenging to identify them due to physiological 18F-FDG uptake. There are no publications demonstrating the application of FDG in post-transplant rejection in humans yet. The aim of this study is to determine the feasibility of suppression of myocardial FDG uptake in post-transplant patients, comparing three different protocols of preparation. METHODS Ten patients after heart transplantation were imaged by FDG associated with three endomyocardial biopsies (EMB), scheduled in the first year after the procedure. Before each imaging, patients were randomized to one of three preparations: (1) hyperlipidic-hypoglycemic diet; (2) fasting longer than 12 hours; and (3) fasting associated with intravenous heparin. All patients would undergo the three methods. FDG images were analyzed using visual analysis scores and relative radiotracer cardiac uptake (RRCU). RESULTS The suppression rate of radiotracer activity ranged from 55% to 62%. Visual analysis showed that preparation 3 presented less efficacy in the suppression compared to the others. However, RRCU did not show difference between the preparations. CONCLUSIONS Suppression of physiological myocardial FDG uptake after cardiac transplantation is feasible. The usefulness of heparin in the suppression is unclear.
Photodynamic therapy for the prevention and treatment of Actinic Keratosis/Squamous cell carcinoma in solid organ transplant recipients: A systematic review and meta-analysis
Journal of the European Academy of Dermatology & Venereology. 2020;34(2):251-259
Solid organ transplant recipients (sOTR) are at an increased risk of developing cutaneous cancers, especially squamous cell carcinoma (SCC). Photodynamic therapy (PDT) for the prevention and treatment of actinic keratosis (AK)/SCC in sOTR is increasingly prescribed given the increase in solid organ transplantations performed worldwide. PDT has added advantages of superior cosmetic outcomes and good safety profile compared to conventional surgical methods and other topical therapies. We aim to evaluate the role of PDT in the prevention and treatment of AK/SCC in sOTRs. The Cochrane Library, PubMed and Embase Database were searched. Articles reporting PDT outcomes amongst sOTR with or without AK/SCC at baseline were selected. We classified the studies into two categories: (1)PDT as prevention measure and (2)treatment of AK/SCC in sOTR. Primary outcome for the prevention category was three-year incidence of AK/SCC and complete response (CR) of lesions after PDT exposure in the treatment category. Secondary outcomes were cosmesis and adverse reaction in both categories. Pooled results were expressed as risk difference (RD) with corresponding 95% confidence interval (95% CI). Twelve out of 641 articles met our eligibility criteria, out of which 4 RCTs reported the preventive effect of AK/SCC and another 5 RCTs reported the treatment effect of PDT in sOTR. One RCT did not report absolute number of lesions at baseline/end of study for results to be pooled in the quantitative analysis. The remaining three studies were cohort studies reporting treatment and preventive effect of PDT in sOTR. PDT group had a lower incidence as a preventive measure with pooled RD of 0.14(95% CI 0.08-0.19). The CR in PDT was higher in the treatment group with a pooled RD of 0.77(95% CI 0.6-0.94) and 0.50 (95% CI 0.22-0.79) in pre-divided lesional areas and number of lesions respectively. In conclusion, PDT is efficacious for prevention and treatment of AK/SCC in sOTRs. This article is protected by copyright. All rights reserved.
Invasive haemodynamics in de novo everolimus vs. calcineurin inhibitor heart transplant recipients
ESC heart failure. 2020;[record in progress]:14
AIMS: Invasive haemodynamic profiles at rest and during exercise after heart transplantation (HTx) have never been described in a randomized trial where de novo everolimus (EVR)-based therapy with early calcineurin inhibitor (CNI) withdrawal has been compared with conventional CNI treatment. We report central invasive haemodynamic parameters at rest and exercise during a 3 year follow-up after HTx in a sub-study of the SCandiavian Heart transplant Everolimus De novo stUdy with earLy calcineurin inhibitor avoidancE trial. We hypothesized that the nephroprotective properties, the less development of cardiac allograft vasculopathy (CAV), and the antifibrotic properties of EVR, in comparison with CNI-based immunosuppression, would demonstrate favourable invasive haemodynamic profiles in patients at rest and during exercise. METHODS AND RESULTS Ninety of 115 HTx recipients randomized to EVR or CNI treatment performed right heart catheterization at rest and 68 performed right heart catheterization at exercise up to 3 years after HTx. Haemodynamic profiles were compared between EVR and CNI treatment groups. Resting haemodynamics improved in both groups from pre-HTx to the first follow-up at 7-11 weeks post-HTx and thereafter remained unchanged up to 3 years of follow-up. During follow-up, cardiac reserve during exercise increased with higher levels of maximum heart rate (118 to 148 b.p.m., P < 0.001), mean arterial pressure (103 to 128 mmHg, P < 0.001), and cardiac output (10.3 to 12.2 l/min, P < 0.001). No significant differences in haemodynamic parameters were observed between the EVR and CNI groups at rest or exercise. Isolated post-capillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure >= 15 mmHg, and pulmonary vascular resistance <3) were measured in 11% of the patients at 7-11 weeks, 5% at 12 months, and 6% at 36 months after HTx. The EVR group had significantly better kidney function (76 mL/min/1 vs. 60 mL/min/1, P < 0.001) and reduced CAV (P < 0.01) but an increased rate of early biopsy-proven treated rejections (21.2% vs 5.7%, P < 0.01) compared with the CNI group at any time point. The differences in renal function, CAV, or early biopsy-proven treated acute rejections were not associated with altered haemodynamics. CONCLUSIONS De novo EVR treatment with early CNI withdrawal compared with conventional CNI therapy did not result in differences in haemodynamics at rest or during exercise up to 3 years after HTx despite significant differences in renal function, reduced CAV, and number of early biopsy-proven treated rejections.
A Randomized Trial of Intravenous Thyroxine for Brain-Dead Organ Donors With Impaired Cardiac Function
Progress in Transplantation. 2020;30(1):48-55
The primary objective of this pilot study was to examine if cardiac function in brain dead (BD) donors exhibiting impaired ejection fraction (EF) could be improved by the infusion of thyroxine (T4).
Donors were randomly assigned to either the T4 group or the placebo group.
28 brain-dead organ donors from 18 to 50 years of age were included in the study.
The primary outcome included improvements in the left ventricular ejection fraction (LVEF) with thyroxine infusion versus no treatment, evaluated using thoracic echocardiogram (TTE) immediately after infusion. The secondary outcome was the porportion of successfully transplanted hearts.
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
This small study from a single organ procurement organization in the US investigated the use of thyroxine in the management of DBD donors with an ejection fraction less than 60%. In the 28 potential donors randomized to T4 or control, no changes were seen in ejection fraction or donation rates between the groups. The study is limited by its small size – of the 28 patients recruited, around 40% did not receive the full treatment with T4 or undergo repeat echo. The lack of power means that no firm conclusion can be made. However, it does nicely demonstrate feasibility,
as well as the challenges to recruitment in a study such as this. Ultimately a larger, definitive study is still needed.
RATIONALE Brain death (BD) precipitates cardiac dysfunction impairing the ability to transplant hearts from eligible organ donors. Retrospective studies have suggested that thyroid hormone may enhance myocardial recovery and increase hearts transplanted. We performed a randomized trial evaluating whether intravenous thyroxine (T4) improves cardiac function in BD donors with impaired ejection fraction (EF). METHODS All heart-eligible donors managed at a single-organ procurement organization (OPO) underwent protocolized fluid resuscitation. Those weaned off vasopressors underwent transthoracic echocardiography (TTE) within 12 hours of BD and, if EF was below 60%, were randomized to T4 infusion or no T4 for 8 hours, after which TTE was repeated. RESULTS Of 77 heart-eligible donors, 36 were weaned off vasopressors. Ejection fraction was depressed in 30, of whom 28 were randomized to T4 (n = 17) vs control (n = 11). Baseline EF was comparable (45%, interquartile range [IQR] 42.5-47.5 vs 40%, 40-50, P = .32). Ejection fraction did not improve more with T4 (10%, IQR 5-15 vs 5%, 0-12.5, P = .24), although there was a trend to more hearts transplanted (59% vs 27%, P = .14). This difference appeared to be accounted for by more donors with a history of drug use in the T4 group, who exhibited greater improvements in EF (15% vs 0% without drug use, P = .01) and more often had hearts transplanted (12 of 19 vs 1 of 9, P = .01). CONCLUSIONS In this small randomized study of BD donors with impaired cardiac function, T4 infusion did not result in greater cardiac recovery. A larger randomized trial comparing T4 to placebo appears warranted but would require collaboration across multiple OPOs.
Association of Clinical Outcomes With Left Ventricular Assist Device Use by Bridge to Transplant or Destination Therapy Intent: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) Randomized Clinical Trial
JAMA Cardiology. 2020;[record in progress]:15
This was a secondary analysis of the MOMENTUM 3 trial which aimed to evaluate the impact of therapeutic intent on the short-term and long term outcomes of HeartMate 3 (HM3) as compared to HeartMate II (HMII) in patients with advanced heart failure.
Patients were randomized in a 1:1 ratio to receive either the the magnetically levitated centrifugal-flow HeartMate 3 (HM3) left ventricular assist device (LVAD) or the the axial-flow HeartMate II (HMII) pump, regardless of the intended goal of therapy (bridge to transplant (BTT)/ bridge to transplant candidacy (BTC) or destination therapy (DT)).
The study enrolled 1028 patients with advanced-stage heart failure that were considered to be candidates for LVAD therapy.
The primary outcome was disabling stroke-free survival or reoperation to either remove or replace an impaired device at 2 years. The secondary outcome were adverse events, rehospitalizations, functional capacity and quality of life.
Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences, University of Oxford
This is another report from the MOMENTUM-3 study comparing a fully magnetically levitated circulatory pump with a commercially available axial-flow pump for advanced heart failure. Previous publications had shown that the centrifugal-flow pump was associated with better outcomes at 6 months than the axial-flow pump. The trial was well-conducted, multicentre, un-blinded and randomised controlled trial with full follow up. The analysis presented here was pre-specified in the protocol. The key aim of this analysis was to see if outcomes with the two LVADs differed by the intended treatment intention of the therapy, as a bridge to transplantation or destination therapy.
The primary end-point was a composite outcome of survival free from disabling stroke or reoperation to remove or replace a malfunctioning device. This outcome was significantly better for patients with the centrifugal-flow pump rather than the axial-flow pump regardless of treatment intention (HR=0.62 if bridge to transplant and HR=0.61 if destination therapy). A test of interaction showed no significant difference between the impact of the LVAD type on the two populations. The centrifugal-flow pump was associated with significantly fewer episodes of pump thrombosis, stroke and bleeding, also irrespective of treatment intention.
Importance: Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant. Objective: To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT). Design, Setting, and Participants: This study was a prespecified secondary analysis of the MOMENTUM 3 trial, a multicenter randomized clinical trial comparing the magnetically levitated centrifugal-flow HeartMate 3 (HM3) LVAD to the axial-flow HeartMate II (HMII) pump. It was conducted in 69 centers with expertise in managing patients with advanced heart failure in the United States. Patients with advanced heart failure were randomized to an LVAD, irrespective of the intended goal of therapy (BTT/BTC or DT). Main Outcomes and Measures: The primary end point was survival free of disabling stroke or reoperation to remove or replace a malfunctioning device at 2 years. Secondary end points included adverse events, functional status, and quality of life. Results: Of the 1020 patients with implants (515 with HM3 devices [50.5%] and 505 with HMII devices [49.5%]), 396 (38.8%) were in the BTT/BTC group (mean [SD] age, 55  years; 310 men [78.3%]) and 624 (61.2%) in the DT group (mean [SD] age, 63  years; 513 men [82.2%]). Of the patients initially deemed as transplant ineligible, 84 of 624 patients (13.5%) underwent heart transplant within 2 years of LVAD implant. In the primary end point analysis, HM3 use was superior to HMII use in patients in the BTT/BTC group (76.8% vs 67.3% for survival free of disabling stroke and reoperation; hazard ratio, 0.62 [95% CI, 0.40-0.94]; log-rank P = .02) and patients in the DT group (73.2% vs 58.7%; hazard ratio, 0.61 [95% CI, 0.46-0.81]; log-rank P < .001). For patients in both BTT/BTC and DT groups, there were not significantly different reductions in rates of pump thrombosis, stroke, and gastrointestinal bleeding with HM3 use relative to HMII use. Improvements in quality of life and functional capacity for either pump were not significantly different regardless of preimplant strategy. Conclusions and Relevance: In this trial, the superior treatment effect of HM3 over HMII was similar for patients in the BTT/BTC or DT groups. It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure. Trial Registration: ClinicalTrials.gov identifier: NCT02224755.