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INTRODUCTION: ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial's innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. AIM: To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. METHODS: PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. RESULTS: PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise 'initial information leaflet' was developed to be sent with the initial invitations, with the 'full' information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. CONCLUSIONS: PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial.
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Diabetes Mellitus Tipo 2 , Participación del Paciente , Proyectos de Investigación , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Hipoglucemiantes/uso terapéutico , Resultado del Tratamiento , Selección de Paciente , Participación de la Comunidad , Administración Oral , Reino Unido , Participación de los Interesados , Péptidos Similares al GlucagónRESUMEN
Growing evidence suggests that ambient air pollution has adverse effects on mental health, yet our understanding of its unequal impact remains limited, especially in areas with historical redlining practices. This study investigates whether the impact of daily fluctuations in ambient air pollutant levels on emergency room (ER) visits for mental disorders (MDs) varies across neighborhoods affected by redlining. Furthermore, we explored how demographic characteristics and ambient temperature may modify the effects of air pollution. To assess the disproportional short-term effects of PM2.5, NO2, and O3 on ER visits across redlining neighborhoods, we used a symmetric bidirectional case-crossover design with a conditional logistic regression model. We analyzed data from 2 million ER visits for MDs between 2005 and 2016 across 17 cities in New York State, where redlining policies were historically implemented. A stratified analysis was performed to examine potential effect modification by individuals' demographic characteristics (sex, age, and race/ethnicity) and ambient temperature. We found that both PM2.5 and NO2 were significantly associated with MD-related ER visits primarily in redlined neighborhoods. Per 10µgm-3 increase in daily PM2.5 and per 10 ppb increase in NO2 concentration were associated with 1.04 % (95 % Confidence Interval (CI): 0.57 %, 1.50 %) and 0.44 % (95 % CI: 0.21 %, 0.67 %) increase in MD-related ER visits in redlined neighborhoods, respectively. We also found significantly greater susceptibility among younger persons (below 18 years old) and adults aged 35-64 among residents in grade C or D, but not in A or B. Furthermore, we found that positive and statistically significant associations between increases in air pollutants (PM2.5 and NO2) and MD-related ER visits exist during medium temperatures (4.90 °C to 21.11 °C), but not in low or high temperature. Exposures to both PM2.5 and NO2 were significantly associated with MD-related ER visits, but these adverse effects were disproportionately pronounced in redlined neighborhoods.
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Contaminantes Atmosféricos , Contaminación del Aire , Exposición a Riesgos Ambientales , Material Particulado , Humanos , New York/epidemiología , Contaminación del Aire/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Material Particulado/análisis , Femenino , Masculino , Adulto , Persona de Mediana Edad , Salud Mental/estadística & datos numéricos , Trastornos Mentales/epidemiología , Adolescente , Adulto Joven , Dióxido de Nitrógeno/análisis , Ciudades , Servicio de Urgencia en Hospital/estadística & datos numéricosRESUMEN
BACKGROUND: As a complementary means to urban public transit systems, public bike-sharing provides a green and active mode of sustainable mobility, while reducing carbon-dioxide emissions and promoting health. There has been increasing interest in factors affecting bike-sharing usage, but little is known about the effect of ambient air pollution. METHOD: To assess the short-term impact of daily exposure to multiple air pollutants (PM2.5, PM10, NO2, and O3) on the public bike-sharing system (PBS) usage in Seoul, South Korea (2018-2021), we applied a quasi-Poisson generalized linear model combined with a distributed lag nonlinear model (DLNM). The model was adjusted for day of the week, holiday, temperature, relative humidity, and long-term trend. We also conducted stratification analyses to examine the potential effect modification by age group, seasonality, and COVID-19. RESULTS: We found that there was a negative association between daily ambient air pollution and the PBS usage level at a single lag day 1 (i.e., air quality a day before the event) across all four pollutants. Our results suggest that days with high levels of air pollutants (at 95th percentile) are associated with a 0.91% (0.86% to 0.96%) for PM2.5, 0.89% (0.85% to 0.94%) for PM10, 0.87% (0.82% to 0.91%) for O3, and 0.92% (0.87% to 0.98%) for NO2, reduction in cycling behavior in the next day compared to days with low levels of pollutants (at 25th percentile). No evidence of effect modification was found by seasonality, age nor the COVID-19 pandemic for any of the four pollutants. CONCLUSIONS: Our findings suggest that high concentrations of ambient air pollution are associated with decreased rates of PBS usage on the subsequent day regardless of the type of air pollutant measured.
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Contaminantes Atmosféricos , Contaminación del Aire , Ciclismo , COVID-19 , Humanos , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminación del Aire/estadística & datos numéricos , Ciclismo/estadística & datos numéricos , COVID-19/epidemiología , Seúl , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Material Particulado/análisis , Material Particulado/efectos adversos , Adulto , Persona de Mediana Edad , Transportes/estadística & datos numéricos , República de Corea , Estaciones del AñoRESUMEN
BACKGROUND: Recent efforts to increase access to kidney transplant (KTx) in the United States include increasing referrals to transplant programs, leading to more pretransplant services. Transplant programs reconcile the costs of these services through the Organ Acquisition Cost Center (OACC). OBJECTIVE: The aim of this study was to determine the costs associated with pretransplant services by applying microeconomic methods to OACC costs reported by transplant hospitals. RESEARCH DESIGN, SUBJECTS, AND MEASURES: For all US adult kidney transplant hospitals from 2013 through 2018 (n=193), we crosslinked the total OACC costs (at the hospital-fiscal year level) to proxy measures of volumes of pretransplant services. We used a multiple-output cost function, regressing total OACC costs against proxy measures for volumes of pretransplant services and adjusting for patient characteristics, to calculate the marginal cost of each pretransplant service. RESULTS: Over 1015 adult hospital-years, median OACC costs attributable to the pretransplant services were $5 million. Marginal costs for the pretransplant services were: initial transplant evaluation, $9k per waitlist addition; waitlist management, $2k per patient-year on the waitlist; deceased donor offer management, $1k per offer; living donor evaluation, procurement and follow-up: $26k per living donor. Longer time on dialysis among patients added to the waitlist was associated with higher OACC costs at the transplant hospital. CONCLUSIONS: To achieve the policy goals of more access to KTx, sufficient funding is needed to support the increase in volume of pretransplant services. Future studies should assess the relative value of each service and explore ways to enhance efficiency.
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Trasplante de Riñón , Listas de Espera , Humanos , Trasplante de Riñón/economía , Trasplante de Riñón/estadística & datos numéricos , Estados Unidos , Masculino , Femenino , Persona de Mediana Edad , Determinación de la Elegibilidad , Adulto , Obtención de Tejidos y Órganos/economía , Costos de la Atención en Salud/estadística & datos numéricosRESUMEN
Purpose: To review the literature reporting on complications and failure rates after primary anterior cruciate ligament reconstruction (ACLR) in patients ≥40 years. Methods: This was a secondary analysis from a prior systematic review of the MEDLINE, CINAHL, SportDiscus, Embase, Web of Science, and Cochrane databases on studies evaluating clinical outcomes in ACLR patients ≥40 years. Studies were included based on the following criteria: English-language studies reporting on postoperative complications and/or ACLR failure rates in patients ≥40 years. Case reports, technical notes, studies with duplicate reporting of patient cohorts, or studies using publicly available registry data were excluded. ACLR failure definitions, failure rates, graft rupture rates, revision ACLR and non-ACLR revision rates, and complication rates were recorded. Results: Twenty-one studies were included following full-text review. Autografts were used in 89.0% of cases. Definitions for ACLR failure varied, ranging from (1) revision ACLR, (2) graft rupture, (3) clinical examination of increased knee laxity, and (4) postoperative arthrofibrosis requiring an additional surgery. The median ACLR failure rate was 5.0% (range, 0%-12.1%) among the 9 studies reporting this outcome, with only 4 of the studies providing explicit definitions of failure. The median ACLR revision surgery, graft rupture, and non-ACLR revision surgery rates were 0% (range, 0%-7.7%), 2.7% (range, 0%-9.1%), and 7.2% (range 0%-34.4%), respectively. Commonly reported complications included pain (range, 0%-14.0%), stiffness (range, 0%-12.7%), hematoma (range, 2.5%-8.8%), neurovascular (range, 0%-41.7%), and undefined (range, 0%-13.8%). Conclusions: ACLR in patients over 40 years old shows low failure rates. Level of Evidence: Level IV, systematic review of Level II-IV studies.
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BACKGROUND: Measuring tissue oxygen concentration is crucial in understanding the pathophysiological process of hypoxia in head and neck cancer (HNC) and its significant role in cancer biology. This study aimed to determine the feasibility of T1 mapping using a variable flip angle (VFA) technique with stack of stars (SOS) trajectory sampling in HNC patients undergoing chemoradiotherapy (CRT). METHODS: To evaluate the ability of SOS acquisition to detect T1, a phantom study was conducted and compared to conventional Cartesian acquisition (CART). Additionally, four newly diagnosed patients were recruited and underwent two scans each at baseline and inter-treatment. The repeatability of SOS and CART acquisitions was assessed by comparing the T1 measurements of CSF from the baseline and intra-treatment MRI studies. The changes in ∆T1 of the tumors during air and oxygen inhalation between baseline and inter-treatment scans were also evaluated. RESULTS: Our study found that the 3D VFA SOS sequence was effective in reducing motion artifacts compared to the conventional VFA sequence with CART sampling and the same scan time, as demonstrated by the results from the phantom and patient studies. In terms of repeatability, no significant correlation was observed between the variability in ΔT1 measurements of CSF obtained from SOS T1 maps. The SOS ΔT1 measurements showed higher consistency, as evidenced by the ICC values ranging from 0.52 to 0.92. The ∆T1 measurements on the primary tumors increased after the first CRT (p<0.05) for all patients who showed a positive treatment response, except for one patient (0.05
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Quimioradioterapia , Estudios de Factibilidad , Neoplasias de Cabeza y Cuello , Imagenología Tridimensional , Imagen por Resonancia Magnética , Fantasmas de Imagen , Humanos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/terapia , Masculino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Femenino , Imagenología Tridimensional/métodos , Reproducibilidad de los Resultados , Anciano , Adulto , Oxígeno , ArtefactosRESUMEN
BACKGROUND: Following the integration of the electronic health record (EHR) into the healthcare system, concern has grown regarding EHR use on physician well-being. For surgical residents, time spent on the EHR increases the burden of a demanding, hourly restricted schedule and detracts from time spent honing surgical skills. To better characterize these burdens, we sought to describe EHR utilization patterns for plastic surgery residents. METHODS: Integrated plastic surgery resident EHR utilization from March 2019 to March 2020 was extracted via Cerner Analytics at a tertiary academic medical center. Time spent in the EHR on-duty (0600-1759) and off-duty (1800-0559) in the form of chart review, orders, documentation, and patient discovery was analyzed. Statistical analysis was performed in the form of independent t tests and Analysis of Variance (ANOVA). RESULTS: Twelve plastic surgery residents spent a daily average of 94 ± 84 minutes on the EHR, one-third of which was spent off-duty. Juniors (postgraduate years 1-3) spent 123 ± 99 minutes versus seniors (postgraduate years 4-6) who spent 61 ± 49 minutes (P < 0.01). Seniors spent 19% of time on the EHR off-duty, compared with 37% for juniors (P < 0.01). Chart review comprised the majority (42%) of EHR usage, followed by patient discovery (22%), orders (14%), documentation (12%), other (6%), and messaging (1%). Seniors spent more time on patient discovery (25% vs 21%, P < 0.001), while juniors spent more time performing chart review (48% vs 36%, P = 0.19). CONCLUSION: Integrated plastic surgery residents average 1.5 hours on the EHR daily. Junior residents spend 1 hour more per day on the EHR, including more time off-duty and more time performing chart review. These added hours may play a role in duty hour violations and detract from obtaining operative skill sets.
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Internado y Residencia , Cirugía Plástica , Humanos , Registros Electrónicos de Salud , Factores de Tiempo , ComputadoresRESUMEN
This cross-sectional study calculates deceased kidney donation rates in the US using deaths compatible with donation as the metric's denominator.
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Mortalidad Hospitalaria , HumanosRESUMEN
Invasive populations often have lower genetic diversity relative to the native-range populations from which they derive.1,2 Despite this, many biological invaders succeed in their new environments, in part due to rapid adaptation.3,4,5,6 Therefore, the role of genetic bottlenecks in constraining the adaptation of invaders is debated.7,8,9,10 Here, we use whole-genome resequencing of samples from a 10-year time-series dataset, representing the natural invasion of the Asian honey bee (Apis cerana) in Australia, to investigate natural selection occurring in the aftermath of a founding event. We find that Australia's A. cerana population was founded by as few as one colony, whose arrival was followed by a period of rapid population expansion associated with an increase of rare variants.11 The bottleneck resulted in a steep loss of overall genetic diversity, yet we nevertheless detected loci with signatures of positive selection during the first years post-invasion. When we investigated the origin of alleles under selection, we found that selection acted primarily on the variation introduced by founders and not on the variants that arose post-invasion by mutation. In all, our data highlight that selection on standing genetic variation can occur in the early years post-invasion, even where founding bottlenecks are severe.
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Variación Genética , Genética de Población , Animales , Abejas , Selección Genética , Análisis de Secuencia de ADN , MutaciónRESUMEN
Volatile methylsiloxanes (VMS) are man-made, nonbiodegradable chemicals produced at a megaton-per-year scale, which leads to concern over their potential for environmental persistence, long-range transport, and bioaccumulation. We used directed evolution to engineer a variant of bacterial cytochrome P450BM3 to break silicon-carbon bonds in linear and cyclic VMS. To accomplish silicon-carbon bond cleavage, the enzyme catalyzes two tandem oxidations of a siloxane methyl group, which is followed by putative [1,2]-Brook rearrangement and hydrolysis. Discovery of this so-called siloxane oxidase opens possibilities for the eventual biodegradation of VMS.
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Numerous United States transplant centers require solid organ transplantation candidates to be vaccinated against the coronavirus disease of 2019 to be active on the United Network for Organ Sharing waiting list. This study examined characteristics of adult patients on one center's kidney transplantation waiting list whose status was inactivated due to a lack of coronavirus disease 2019 vaccination by July 1, 2022, and who did not subsequently provide proof of vaccination by August 31, 2022 (cases). Patients in the control group were retrospectively matched to patients in the case group in a 4-to-1 fashion according to age, sex, and "active" status on the waiting list. Multivariable logistic regression was performed, with race/ethnicity, primary language, health insurance, education, and Vaccine Equity Metric (VEM, a measure of health equity at the zip code level) quartile as covariates. Results revealed that patients from zip codes in the lowest VEM quartile (odds ratio [OR] 1.89; P = .02) and those insured by governmental payors (Medicare: OR, 2.00; P < .01 and Medicaid: OR, 2.89; P < .01) had higher odds of being inactivated than those from zip codes that make up the highest VEM quartile and those insured by commercial payors, respectively. These findings serve as a cautionary tale regarding universal pretransplantation vaccination requirements, which may raise equity concerns that should be considered upon policy implementation.
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COVID-19 , Listas de Espera , Adulto , Humanos , Anciano , Estados Unidos/epidemiología , Estudios de Casos y Controles , Estudios Retrospectivos , Medicare , COVID-19/epidemiología , COVID-19/prevención & control , VacunaciónRESUMEN
OBJECTIVE: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Adulto , Humanos , Trasplante de Hígado/métodos , Donadores Vivos , Recurrencia Local de Neoplasia/etiología , Selección de Paciente , América del Norte , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Anemia de Células Falciformes , Colchicina , Humanos , Ratones , Animales , Colchicina/farmacología , Colchicina/uso terapéutico , Modelos Animales de Enfermedad , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Inflamación/tratamiento farmacológico , Inflamación/genética , Ratones TransgénicosRESUMEN
Crop-raiding by elephants is one of the most prevalent forms of human-elephant conflict and is increasing with the spread of agriculture into wildlife range areas. As the magnitude of conflicts between people and elephants increases across Africa and Asia, mitigating and reducing the impacts of elephant crop-raiding has become a major focus of conservation intervention. In this study, we tested the responses of semi-captive elephants to the "smelly" elephant repellent, a novel olfactory crop-raiding mitigation method. At two trial sites, in Zambia and Thailand, African elephants (Loxodonta africana) and Asian elephants (Elephas maximus) were exposed to the repellent, in order to test whether or not they entered an area protected by the repellent and whether they ate the food provided. The repellent elicited clear reactions from both study groups of elephants compared to control conditions. Generalised linear models revealed that the elephants were more alert, sniffed more, and vocalised more when they encountered the repellent. Although the repellent triggered a response, it did not prevent elephants from entering plots protected by the repellent or from eating crops, unlike in trials conducted with wild elephants. Personality played a role in responses towards the repellent, as the elephants that entered the experimental plots were bolder and more curious individuals. We conclude that, although captive environments provide controlled settings for experimental testing, the ecological validity of testing human-elephant conflict mitigation methods with captive wildlife should be strongly considered. This study also shows that understanding animal behaviour is essential for improving human-elephant coexistence and for designing deterrence mechanisms. Appreciating personality traits in elephants, especially amongst "problem" elephants who have a greater propensity to crop raid, could lead to the design of new mitigation methods designed to target these individuals.
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A variety of mouse models for Down syndrome (Trisomy 21) have been created to test hypotheses about the correlation of phenotypes to gene content and copy number. Ts1Rhr mice are trisomic for a region on mouse chromosome 16 that is homologous to 5.3 Mb of human chromosome 21. Ms1Rhr mice are monosomic for this region. Magnetic Resonance Imaging (MRI) has revealed characteristic volumetric changes in the brains of humans with Down syndrome such as reductions in the cerebellum, hippocampus, and brain stem, and increases in the ventricles and thalamus. We used MRI with region of interest analysis to measure the volume of the thalamus and hypothalamus in Ts1Rhr, Ms1Rhr, and euploid control mice (n = 10-11 per group). Ts1Rhr mice had a 6.6% reduction and Ms1Rhr mice had an 8.2% reduction in the volume of the thalamus. Ts1Rhr and Ms1Rhr hypothalamic volumes were equivalent to controls. Conflicting data in mouse models show a lack of clarity on causative roles of regions homologous to human chromosome 21 in phenotypes related to the thalamus and hypothalamus in Down syndrome.
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Chronic cluster headache (CCH) is a debilitating primary headache that causes excruciating pain without remission. Various medical and surgical treatments have been implemented over the years, yet many provide only short-term relief. Deep brain stimulation (DBS) is an emerging treatment alternative that has been shown to dramatically reduce the intensity and frequency of headache attacks. However, reports of greater than 10-year outcomes after DBS for CCH are scant. Here, we report the durability of DBS in the posterior inferior hypothalamus after 10 years on a patient with CCH. Our patient experienced an 82% decrease in the frequency of headaches after DBS, which was maintained for over 10 years. The side effects observed included depression, irritability, anxiety, and dizziness, which were alleviated by changing programming settings. In the context of current literature, DBS shows promise for long-term relief of cluster headaches when other treatments fail.
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Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.
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Trasplante de Riñón , Obtención de Tejidos y Órganos , Humanos , Estados Unidos , Donadores Vivos , Riñón , Encuestas y CuestionariosRESUMEN
Introduction: Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. Methods: We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. Results: In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). Discussion: In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.
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Líquidos Corporales , Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Enfermedad Hepática en Estado Terminal/cirugía , Índice de Severidad de la Enfermedad , Donantes de TejidosRESUMEN
Small-for-size syndrome (SFSS) following living donor liver transplantation is a complication that can lead to devastating outcomes such as prolonged poor graft function and possibly graft loss. Because of the concern about the syndrome, some transplants of mismatched grafts may not be performed. Portal hyperperfusion of a small graft and hyperdynamic splanchnic circulation are recognized as main pathogenic factors for the syndrome. Management of established SFSS is guided by the severity of the presentation with the initial focus on pharmacological therapy to modulate portal flow and provide supportive care to the patient with the goal of facilitating graft regeneration and recovery. When medical management fails or condition progresses with impending dysfunction or even liver failure, interventional radiology (IR) and/or surgical interventions to reduce portal overperfusion should be considered. Although most patients have good outcomes with medical, IR, and/or surgical management that allow graft regeneration, the risk of graft loss increases dramatically in the setting of bilirubin >10 mg/dL and INR>1.6 on postoperative day 7 or isolated bilirubin >20 mg/dL on postoperative day 14. Retransplantation should be considered based on the overall clinical situation and the above postoperative laboratory parameters. The following recommendations focus on medical and IR/surgical management of SFSS as well as considerations and timing of retransplantation when other therapies fail.