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Criollo cattle, the descendants of animals brought by Iberian colonists to the Americas, have been the subject of natural and human-mediated selection in novel tropical agroecological zones for centuries. Consequently, these breeds have evolved distinct characteristics such as resistance to diseases and exceptional heat tolerance. In addition to European taurine (Bos taurus) ancestry, it has been proposed that gene flow from African taurine and Asian indicine (Bos indicus) cattle has shaped the ancestry of Criollo cattle. In this study, we analysed Criollo breeds from Colombia and Venezuela using whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) array data to examine population structure and admixture at high resolution. Analysis of genetic structure and ancestry components provided evidence for African taurine and Asian indicine admixture in Criollo cattle. In addition, using WGS data, we detected selection signatures associated with a myriad of adaptive traits, revealing genes linked to thermotolerance, reproduction, fertility, immunity and distinct coat and skin coloration traits. This study underscores the remarkable adaptability of Criollo cattle and highlights the genetic richness and potential of these breeds in the face of climate change, habitat flux and disease challenges. Further research is warranted to leverage these findings for more effective and sustainable cattle breeding programmes.
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Background and aims: Computed tomography (CT), often more accessible than magnetic resonance imaging (MRI), remains widely used though radiation exposure is an obvious disadvantage. We previously showed that modern CT technology can achieve over 70% reduction in radiation-dose without loss of accuracy. Here, we compare low- versus conventional-dose CT in patients with known Crohn's disease to assess clinical confidence and accuracy of the low-dose procedure in the semi-acute setting.Methods: A comparative study of low-dose CT with full iterative reconstruction (IR) versus conventional-dose CT was conducted in 50 consecutive outpatients with Crohn's disease. Clinicians were provided with the low-dose images and reports, whereas conventional-dose images were reviewed after 4 weeks.Results: The clinical question was adequately addressed with low-dose IR imaging in all cases. Complications of Crohn's were detected in 37/50 (74%) with no disagreement between low- and conventional-dose imaging. The effective radiation dose reduction was 76.5% (low-dose mean 2.15 mSv versus conventional-dose CT 6.99 mSv).Conclusion: Low-dose IR CT is safe and accurate for evaluating distribution and complications of known Crohn's disease in the outpatient setting. We propose that low-dose radiation imaging should be adopted as standard-of-care for the evaluation of Crohn's disease and an acceptable alternative to MR particularly in the acute setting. ClinicalTrials.gov: NCT03140306.
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Enfermedad de Crohn , Exposición a la Radiación , Tomografía Computarizada por Rayos X/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Enfermedad de Crohn/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Dosis de RadiaciónRESUMEN
Liver disease, of which liver cirrhosis is the most advanced stage, constitutes the fourth most common cause of life-years lost in men and women younger than 75 years in England, where mortality rates from liver disease have increased by 25% in the past decade. Alcohol consumption is the most common modifiable risk factor for disease progression in these individuals, but within the UK, there is substantial variation in the distribution, prevalence, and outcome of alcohol-related liver disease, and no equity of access to tertiary transplantation services. These revised recommendations were agreed by an expert panel convened by the UK Liver Advisory Group, with the purpose of providing consensus on referral for transplant assessment in patients with alcohol-related disease, and clarifying the terminology and definitions of alcohol use in liver injury. By standardising clinical management in these patients, it is hoped that there will be an improvement in the quality of care and better access to liver transplant assessment for patients with alcohol-related liver disease in the UK.
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Hepatopatías Alcohólicas/cirugía , Trasplante de Hígado/normas , Derivación y Consulta/normas , Toma de Decisiones Clínicas/métodos , Accesibilidad a los Servicios de Salud/normas , Disparidades en Atención de Salud , Humanos , Hepatopatías Alcohólicas/diagnóstico , Selección de Paciente , Reino UnidoAsunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Quimioradioterapia/efectos adversos , Hemorragia Gastrointestinal/tratamiento farmacológico , Terapia Neoadyuvante/efectos adversos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Femenino , Hemorragia Gastrointestinal/etiología , Hemostasis Endoscópica , Humanos , Persona de Mediana Edad , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Precision nutrition and personalized diets are gaining popularity in nutritional science and medicine. To fully appreciate their potential benefits, a deep understanding of both macronutrients and nutrient-microbe interactions is required. RECENT FINDINGS: Microbiome science has reaffirmed the importance of dietary fiber in microbial and host health. Additional macronutrients, digestible carbohydrate, protein and fat also influence the composition and diversity of the microbiome and, therefore, microbial response to dietary intervention. Attention to macronutrient source, dose, microbial effect and metabolite production allows the development of more established links between diet and health. SUMMARY: The degree to which human diets need to be personalized for optimal health is still uncertain but a one-size-fits-all diet seems unlikely. However, for personal or precision nutrition to fulfill its promise, greater attention to the details of nutrient-microbe interactions will be required.
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Microbiota , Nutrientes , Dieta , Fibras de la Dieta , Humanos , Estado NutricionalRESUMEN
Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23-1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99-1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21-3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31-2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables.
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This review presents the results of a study into the offering of rapid microbial detection assays to the Irish dairy industry. At the outset, a consultation process was undertaken whereby key stakeholders were asked to compile a list of the key microorganisms of interest to the sector. The resultant list comprises 19 organisms/groups of organisms divided into five categories: single pathogenic species (Cronobacter sakazakii, Escherichia coli and Listeria monocytogenes); genera containing pathogenic species (Bacillus, Clostridium, Listeria, Salmonella; Staphylococcus); broad taxonomic groupings (Coliforms, Enterobacteriaceae, fecal Streptococci, sulfite reducing bacteria/sulfite reducing Clostridia [SRBs/SRCs], yeasts and molds); organisms displaying certain growth preferences or resistance as regards temperature (endospores, psychrotrophs, thermodurics, thermophiles); indicators of quality (total plate count, Pseudomonas spp.). A survey of the rapid assays commercially available for the 19 organisms/groups of organisms was conducted. A wide disparity between the number of rapid tests available was found. Four categories were used to summarize the availability of rapid assays per organism/group of organisms: high coverage (>15 assays available); medium coverage (5-15 assays available); low coverage (<5 assays available); no coverage (0 assays available). Generally, species or genera containing pathogens, whose presence is regulated-for, tend to have a good selection of commercially available rapid assays for their detection, whereas groups composed of heterogenous or even undefined genera of mainly spoilage organisms tend to be "low coverage" or "no coverage." Organisms/groups of organisms with "low coverage" by rapid assays include: Clostridium spp.; fecal Streptococci; and Pseudomonas spp. Those with "no coverage" by rapid assays include: endospores; psychrotrophs; SRB/SRCs; thermodurics; and thermophiles. An important question is: why have manufacturers of rapid microbiological assays failed to respond to the necessity for rapid methods for these organisms/groups of organisms? The review offers explanations, ranging from the technical difficulty involved in detecting as broad a group as the thermodurics, which covers the spores of multiple sporeforming genera as well at least six genera of mesophilic nonsporeformers, to the taxonomically controversial issue as to what constitutes a fecal Streptococcus or SRBs/SRCs. We review two problematic areas for assay developers: validation/certification and the nature of dairy food matrices. Development and implementation of rapid alternative test methods for the dairy industry is influenced by regulations relating to both the microbiological quality standards and the criteria alternative methods must meet to qualify as acceptable test methods. However, the gap between the certification of developer's test systems as valid alternative methods in only a handful of representative matrices, and the requirement of dairy industries to verify the performance of alternative test systems in an extensive and diverse range of dairy matrices needs to be bridged before alternative methods can be widely accepted and adopted in the dairy industry. This study concludes that many important dairy matrices have effectively been ignored by assay developers.
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Productos Lácteos/microbiología , Industria Lechera , Microbiología de Alimentos , Bacterias/clasificación , Bacterias/aislamiento & purificación , Productos Lácteos/clasificación , Inocuidad de los Alimentos , Hongos/aislamiento & purificación , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Radical changes to clinical and endoscopy practice have been rapidly introduced following the spread of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Urgent endoscopies are, however, intended to proceed as normal with additional personal protective procedures. A perceived reduction in hospital attendances may suggest a number of urgently indicated endoscopic retrograde cholangio-pancreatographies (ERCPs) are being missed. Objectives and Methods: A review of all ERCPs carried out in a large tertiary referral endoscopy unit under healthcare restrictions was compared to the same time period in previous years. The intention was to determine if ERCPs are proceeding as normal or if there is a difference in referral characteristics. RESULTS: Under service restrictions (13 March to the end of April 2020), 55 ERCPs were performed compared with 87 ERCPs in 2019. Similar numbers to 2019 were also recorded in the preceding years. One case of coronavirus disease 2019 (COVID-19) was reported in a patient in the days following ERCP, with no cases notified among staff related to endoscopy. CONCLUSIONS: A reduction in ERCP referrals raises concern that a cohort of patients with significant biliary disease remain undetected. Whether this results in later, and more severe, presentation remains to be seen but a potential surge in such cases could significantly burden all future endoscopy planning services.
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Colangiopancreatografia Retrógrada Endoscópica/estadística & datos numéricos , Infecciones por Coronavirus/epidemiología , Infección Hospitalaria/prevención & control , Pandemias/estadística & datos numéricos , Neumonía Viral/epidemiología , Derivación y Consulta/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , COVID-19 , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudios de Cohortes , Infecciones por Coronavirus/prevención & control , Infección Hospitalaria/epidemiología , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Control de Infecciones/organización & administración , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Neumonía Viral/prevención & control , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Acute kidney injury (AKI) after liver transplantation (LT) is a common problem with complex management. The aims were to analyze the profile of AKI-RIFLE categories in the post-transplant setting of a wide multicentre cohort of patients in the MELD era and to specifically determine the effect of tacrolimus-based (TACRO) immunosuppressive regimes on the development of AKI. METHODS: A retrospective analysis of 550 (2007-2012) consecutive patients transplanted at Reina Sofia, Cordoba, and King's College Hospital, London, was performed. Inclusion criterion was to have CNI as part of initial immunosuppression immediately after LT. RESULTS: After exclusion criteria, a total of 477 patients were analyzed. Incidence of AKI within the first 2 weeks after LT was 65.8% (AKI-Risk), 41.3% (AKI-Injury), and 12.3% (AKI-Failure). The development of any type of AKI had no impact on short- and/or long-term survival up to 3 years after the transplant. Moreover, AKI was almost universal in the early post-transplant period and TACRO trough concentrations during the first 2 weeks after the transplant were not predictors of AKI in none of its categories in the multivariate analyses. CONCLUSIONS: Low-TACRO-based regimes were not as useful as expected in the prevention of AKI when analyzed in the context of a large contemporary LT series.
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Lesión Renal Aguda , Trasplante de Hígado , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Humanos , Inmunosupresores/efectos adversos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/efectos adversosRESUMEN
BACKGROUND & AIMS: The impact of gender and donor/recipient gender mismatch on LT outcomes is controversial. The aim of this study was to compare outcomes of LT in Europe, using the ELTR database, between male and female recipients, including donor/recipient gender mismatch. METHODS: Recipient, donor and transplant characteristics were compared between male and female patients. Patient survival was compared between groups, and the impact of donor/recipient gender matching as well as donor and recipient anthropometric characteristics were evaluated as potential risk factors for post-LT death/graft loss. RESULTS: A total of 46,334 LT patients were evaluated (70.5% men and 29.5% women). Ten-year survival rate was significantly higher in female than in male recipients (66% vs 59%, P < .0001). At multivariate analysis, adjusted for indication to LT and type of graft, donor/recipient gender mismatch (HR 1.12, 95% CI 1.04-1.2; P = .003), donor age > 60 years (HR 1.09, 95% CI 1.01-1.18; P = .027) and recipient age (HR 1.02, 95% CI 1.1-1.02; P < .0001) were significantly associated with post-LT lower survival rate in men. Conversely in female recipients, donor BMI > 30 (HR 1.32, 95% CI 1.09-1.6; P = .005), donor age > 60 years (HR 1.15, 95% CI 1.01-1.32; P = .027) and recipient age (HR 1.02, 95% CI 1.01-1.02; P < .0001) were significantly associated with lower post-LT survival rate. CONCLUSIONS: Donor/recipient gender mismatch in male recipients and the use of obese donor in female recipients are associated with reduced survival after LT. Therefore, the incorporation of donor and recipient anthropometric quantities in the allocation process should be a matter of further studies, as their matching can significantly influence long-term outcomes.
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Trasplante de Hígado , Europa (Continente) , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Donantes de TejidosRESUMEN
The aim of this study was to produce a prognostic model to help predict posttransplant survival in patients transplanted with grade-3 acute-on-chronic liver failure (ACLF-3). Patients with ACLF-3 who underwent liver transplantation (LT) between 2007 and 2017 in 5 transplant centers were included (n = 152). Predictors of 1-year mortality were retrospectively screened and tested on a single center training cohort and subsequently tested on an independent multicenter cohort composed of the 4 other centers. Four independent pretransplant risk factors were associated with 1-year mortality after transplantation in the training cohort: age ≥53 years (P = .044), pre-LT arterial lactate level ≥4 mml/L (P = .013), mechanical ventilation with PaO2 /FiO2 ≤ 200 mm Hg (P = .026), and pre-LT leukocyte count ≤10 G/L (P = .004). A simplified version of the model was derived by assigning 1 point to each risk factor: the transplantation for Aclf-3 model (TAM) score. A cut-off at 2 points distinguished a high-risk group (score >2) from a low-risk group (score ≤2) with 1-year survival of 8.3% vs 83.9% respectively (P < .001). This model was subsequently validated in the independent multicenter cohort. The TAM score can help stratify posttransplant survival and identify an optimal transplantation window for patients with ACLF-3.
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Insuficiencia Hepática Crónica Agudizada , Trasplante de Hígado , Enfermedad Crítica , Humanos , Cirrosis Hepática/cirugía , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Background and study aims Determining the etiology and location of gastrointestinal motility disorders can be challenging. A range of investigations targeting specific areas of gastrointestinal transit are available, but many provide clinical data for a given gastrointestinal region alone or for non-specific whole gut transit, and are otherwise of limited use. Video capsule endoscopy allows endoscopic visualisation of the entire gastrointestinal tract, and may also provide more specific data for regional transit time abnormalities. Patients and methods Data from video capsules ingested by 71 ambulatory healthy subjects were recorded and analyzed to determine gastric and small bowel transit times in the fasting state. Results Median, and interquartile range (IQR), gastric transit time was 22 (10-48) minutes, and median (IQR) small bowel transit time was 198.5 (157-240.5) minutes. Conclusion These data, for the first time to our knowledge, provide references for gastrointestinal transit times among healthy ambulatory subjects using video capsule endoscopy. This potentially strengthens clinical use of video capsule endoscopy in the investigation of patients with suspected gastrointestinal motility disorders.
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The aim of this study was to analyze longterm patient and graft survival after liver transplantation for autoimmune hepatitis (AIH-LT) from the prospective multicenter European Liver Transplant Registry. Patient and liver graft survival between 1998 and 2017 were analyzed. Patients after AIH-LT (n = 2515) were compared with patients receiving LT for primary biliary cholangitis (PBC-LT; n = 3733), primary sclerosing cholangitis (PSC-LT; n = 5155), and alcohol-related cirrhosis (AC-LT; n = 19,567). After AIH-LT, patient survival was 79.4%, 70.8%, and 60.3% and graft survival was 73.2%, 63.4%, and 50.9% after 5, 10, and 15 years of follow-up. Overall patient survival was similar to patients after AC-LT (P = 0.44), but worse than after PBC-LT (hazard ratio [HR], 1.48; P < 0.001) and PSC-LT (HR, 1.19; P = 0.002). AIH-LT patients were at increased risk for death (HR, 1.37-1.84; P < 0.001) and graft loss (HR, 1.35-1.80; P < 0.001) from infections compared with all other groups and had a particularly increased risk for lethal fungal infections (HR, 3.38-4.20; P ≤ 0.004). Excluding patients who died within 90 days after LT, risk of death after AIH-LT was superior compared with AC-LT (HR, 0.84; P = 0.004), worse compared with PBC-LT (HR, 1.38; P < 0.001) and similar compared with PSC-LT (P = 0.93). Autoimmune hepatitis (AIH) patients with living donor liver transplantation (LDLT) showed reduced survival compared with patients receiving donation after brain death (HR, 1.96; P < 0.001). In AIH-LT patients, overall survival is inferior to PBC-LT and PSC-LT. The high risk of death after AIH-LT is caused mainly by early fatal infections, including fungal infections. Patients with LDLT for AIH show reduced survival.
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Colangitis Esclerosante , Hepatitis Autoinmune , Cirrosis Hepática Biliar , Trasplante de Hígado , Colangitis Esclerosante/cirugía , Hepatitis Autoinmune/epidemiología , Hepatitis Autoinmune/cirugía , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Estudios Prospectivos , Sistema de RegistrosRESUMEN
The use of once-daily extended-release tacrolimus (ERT) is associated with improved long-term graft and patient survival when compared with twice-daily tacrolimus (BDT), but the underlying reasons for differential survival are unclear. The aim of the study was to compare clinical outcomes known to impact on posttransplant survival for de novo BDT and ERT in liver transplantation (LT) recipients. METHODS: We conducted a single-center, prospective sequential cohort analysis of adult patients undergoing LT during a change in protocol from de novo BDT to ERT, with a 6-month post-LT follow-up. RESULTS: A total of 160 transplanted patients were evaluated; 82 were in the BDT group and 78 were in the ERT group. The cohorts were matched for standard variables and a similar proportion in each group received induction interleukin-2 receptor antibody (36% and 31%). There were no significant differences in the measured outcomes of patient and graft survival, biopsy-proven acute rejection episodes, post LT diabetes, and toxicity. A significantly lower number of patients developed chronic kidney disease Stage3-4 in the ERT cohort compared with BDT cohort. In patients with pre-LT renal dysfunction who received antibody induction, estimated glomerular filtration rate decreased significantly in the BDT but not the ERT group. CONCLUSIONS: We show that once-daily ERT is as safe and efficacious as BDT in de novo LT but optimally conserves renal function post-LT.
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OBJECTIVE: Hepatocellular carcinoma (HCC) is a complication of the common genetic condition hereditary hemochromatosis (HH). It is unknown whether HH as an etiology of liver disease impacts the outcome. We compared the results of liver transplantation (LT), surgical resection and locoregional therapies in a matched cohort study and investigated whether HH as an etiology has an impact on survival. MATERIALS AND METHODS: Consecutive patients with HH and HCC (2000 to 2015) were compared with age, sex and Barcelona Clinic Liver Cancer (BCLC) stage-matched non-HH HCC cases. Patients were offered curative or noncurative treatment according to BCLC stage and Milan criteria. The primary endpoint was all-cause mortality. RESULTS: A total of 102 patients (52 HH; total cohort median age: 67 [44 to 78] y, 97% male, Model for End-stage Liver Disease: 9 [5 to 31]) were studied with a median follow-up of 22 (3 to 126) months. Of the HH cases, the median serum ferritin at diagnosis of HCC was 326 (27 to 5718) µg/L and α-fetoprotein 33 (2 to 197,926) kIU/L. Five-year survival for HH patients receiving curative therapy was 77% (80% for LT, 67% for resection/radiofrequency ablation), and 15% (23% for transarterial chemoembolization) for those undergoing noncurative therapy. Survival for HH patients compared with controls was similar (hazard ratio=0.949; P=0.839). On multivariate Cox regression survival analysis, BCLC stage, and diagnosis of ischemic heart disease (but not HH diagnosis) were independently associated with reduced survival. CONCLUSIONS: Patients with HCC and HH can achieve comparable survival rates following curative or LRT modalities to other liver diseases. The BCLC staging system accurately stratifies survival and excellent 5-year survival is possible following LT in selected patients.
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Carcinoma Hepatocelular/mortalidad , Causas de Muerte , Hemocromatosis/patología , Neoplasias Hepáticas/mortalidad , Lesiones Precancerosas/mortalidad , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Estudios de Casos y Controles , Ablación por Catéter/métodos , Ablación por Catéter/mortalidad , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/mortalidad , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Hemocromatosis/mortalidad , Hemocromatosis/terapia , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , España , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study. METHODS: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score-matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004). RESULTS: In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T. CONCLUSIONS: PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.
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Inhibidores de la Calcineurina/administración & dosificación , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Tacrolimus/administración & dosificación , Anciano , Inhibidores de la Calcineurina/efectos adversos , Preparaciones de Acción Retardada , Composición de Medicamentos , Europa (Continente) , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Humanos , Inmunosupresores/efectos adversos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tacrolimus/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. METHODS: We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. RESULTS: Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P = .0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P = .0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. CONCLUSIONS: In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Bifidobacterium breve/crecimiento & desarrollo , Microbioma Gastrointestinal , Intestino Delgado/efectos de los fármacos , Intestino Delgado/microbiología , Probióticos/administración & dosificación , Úlcera/prevención & control , Adolescente , Adulto , Endoscopía Capsular , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Intestino Delgado/patología , Irlanda , Masculino , Probióticos/efectos adversos , Factores de Tiempo , Úlcera/inducido químicamente , Úlcera/microbiología , Úlcera/patología , Adulto JovenRESUMEN
BACKGROUND & AIMS: Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors. METHODS: We analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival. RESULTS: Among 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH - an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, pâ¯<0.001). NASH was not significantly associated with survival of patients (hazard ratio [HR] 1.02, pâ¯=â¯0.713) or grafts (HR 0.99; pâ¯=â¯0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61-65â¯years: HR 2.07, pâ¯<0.001; >65: HR 1.72, pâ¯=â¯0.017), elevated model for end-stage liver disease score (>23: HR 1.48, pâ¯=â¯0.048) and low (<18.5â¯kg/m2: HR 4.29, pâ¯=â¯0.048) or high (>40â¯kg/m2: HR 1.96, pâ¯=â¯0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors. CONCLUSIONS: The number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications. LAY SUMMARY: The prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.