Graft Survival in Liver Transplantation: An Artificial Neuronal Network Assisted Analysis of the Importance of Comorbidities.

OBJECTIVES: Liver transplant represents a widespread therapeutic option for patients with end-stage liver failure. Up to now, most of the scores describing the probability of liver graft survival have shown poor predictive performance. With this in mind, the present study seeks to analyze the predictive value of recipient comorbidities on liver graft survival within the first year. MATERIALS AND METHODS: The study included prospectively collected data from patients who received a liver transplant at our center from 2010 to 2021. A predictive model was then developed through an Artificial Neural Network that included the parameters associated with graft loss as identified by the Spanish Liver Transplant Registry report and comorbidities with prevalence >2% present in our study cohort. RESULTS: Most patients in our study were men (75.5%); mean age was 54.8 ± 9.6 years. The main cause of transplant was cirrhosis (86.7%), and 67.4% of patients had some associated comorbidities. Graft loss due to retransplant or death with dysfunction occurred in 14% of cases. Of all the variables analyzed, we found 3 comorbidities associated with graft loss (as shown by informative value and normalized informative value, respectively): antiplatelet and/or anticoagulants treatments (0.124 and 78.4%), previous immunosuppression (0.110 and 69.6%), and portal thrombosis (0.105 and 66.3%). Remarkably, our model showed a C statistic of 0.745 (95% CI, 0.692-0.798; asymptotic P < .001), which was higher than others found in previous studies. CONCLUSIONS: Our model identified key parameters that may influence graft loss, including specific recipient comorbidities. The use of artificial intelligence methods could reveal connections that may be overlooked by conventional statistics.

Design of a new mortality indicator in acute coronary syndrome on admission to the Intensive Care Unit.

OBJECTIVE: To design a mortality indicator in acute coronary syndrome (ACS) in the intensive care unit (ICU). DESIGN: A multicenter, observational descriptive study was carried out. PARTICIPANTS: Patients with ACS admitted to the ICUs included in the ARIAM-SEMICYUC registry between January 2013 and April 2019. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Demographic parameters, time of access to the healthcare system, and clinical condition. Revascularization therapy, drugs and mortality were analyzed. Cox regression analysis was performed, followed by the design of a neural network. A receiver operating characteristic curve (ROC) was plotted to calculate the power of the new score. Lastly, the clinical utility or relevance of the ARIAM indicator (ARIAM's) was assessed using a Fagan test. RESULTS: A total of 17,258 patients were included in the study, with a mortality rate of 3.5% (n = 605) at discharge from the ICU. The variables showing statistical significance (P < .001) were entered into the supervised predictive model, an artificial neural network. The new ARIAM's yielded a mean of 0.0257 (95%CI: 0.0245-0.0267) in patients discharged from the ICU versus 0.27085 (95%CI: 0.2533-0.2886) in those who died (P < .001). The area under the ROC curve of the model was 0.918 (95%CI: 0.907-0.930). Based on the Fagan test, the ARIAM's showed the mortality risk to be 19% (95%CI: 18%-20%) when positive and 0.9% (95%CI: 0.8%-1.01%) when negative. CONCLUSIONS: A new mortality indicator for ACS in the ICU can be established that is more accurate and reproducible, and periodically updated.

Encefalitis como manifestación neurológica del COVID-19 / Encephalitis as a neurological manifestation of COVID-19

Introducción: En el contexto de la pandemia mundial por COVID-19, las distintas manifestaciones clínicas de esta infección suponen un reto para los profesionales sanitarios. La afectación respiratoria, síntoma principal de la infección por SARS-CoV-2, hace que otras manifestaciones, como las neurológicas, pasen a un segundo plano, con el consecuente retraso en el diagnóstico y tratamiento.Material y métodosTodo paciente COVID-19 que ha ingresado con sintomatología neurológica o diagnosticado de encefalitis desde marzo de 2020 en un hospital de tercer nivel en Zaragoza, España.ResultadosDos pacientes con infección COVID-19 confirmada por reacción en cadena de la polimerasa (PCR) nasofaríngea y cuyo cuadro clínico consistía en alteraciones neurológicas compatibles con encefalitis. La microbiología del líquido cefalorraquídeo (LCR) fue negativa para bacterias y virus, incluido el SARS-CoV-2 pero, ante la sospecha clínica de encefalitis por este último, se instauró tratamiento antiviral, con inmunoglobulinas y plasmaféresis de forma precoz. A pesar de ello la evolución no fue satisfactoria.ConclusionesLa encefalitis por COVID-19 es una entidad clínica descrita recientemente, cuya fisiopatología aún se desconoce y no se dispone, hasta la fecha, de un tratamiento con evidencia clínica. (AU)

Introduction: In the context of the global COVID-19 pandemic, the different clinical manifestations of this infection pose a challenge for healthcare professionals. Respiratory involvement, the main symptom of SARS-CoV-2 infection, means that other manifestations, such as neurological, take a back seat, with the consequent delay in diagnosis and treatment.Material and methodsAll COVID-19 patients admitted with neurological symptoms or diagnosed with encephalitis since March 2020 in a tertiary hospital in Zaragoza, Spain.ResultsTwo patients with COVID-19 infection confirmed by nasopharyngeal PCR and whose clinical picture consisted of neurological alterations compatible with encephalitis. Cerebrospinal fluid (CSF) microbiology was negative for bacteria and viruses, including SARS-CoV-2 but, given the clinical suspicion of encephalitis due to the latter, antiviral treatment with immunoglobulins and plasmapheresis was started early. Despite this, the evolution was not satisfactory.ConclusionsCOVID-19 encephalitis is a recently described clinical entity, whose pathophysiology is still unknown and no treatment with clinical evidence is available to date. (AU)

Encephalitis as a neurological manifestation of COVID-19.

INTRODUCTION: In the context of the global COVID-19 pandemic, the different clinical manifestations of this infection pose a challenge for healthcare professionals. Respiratory involvement, the main symptom of SARS-CoV-2 infection, means that other manifestations, such as neurological, take a back seat, with the consequent delay in diagnosis and treatment. MATERIAL AND METHODS: All COVID-19 patients admitted with neurological symptoms or diagnosed with encephalitis since March 2020 in a tertiary hospital in Zaragoza, Spain. RESULTS: Two patients with COVID-19 infection confirmed by nasopharyngeal PCR and whose clinical picture consisted of neurological alterations compatible with encephalitis. Cerebrospinal fluid (CSF) microbiology was negative for bacteria and viruses, including SARS-CoV-2 but, given the clinical suspicion of encephalitis due to the latter, antiviral treatment with immunoglobulins and plasmapheresis was started early. Despite this, the evolution was not satisfactory. CONCLUSIONS: COVID-19 encephalitis is a recently described clinical entity, whose pathophysiology is still unknown and no treatment with clinical evidence is available to date.

INTRODUCCIÓN: En el contexto de la pandemia mundial por COVID-19, las distintas manifestaciones clínicas de esta infección suponen un reto para los profesionales sanitarios. La afectación respiratoria, síntoma principal de la infección por SARS-CoV-2, hace que otras manifestaciones, como las neurológicas, pasen a un segundo plano, con el consecuente retraso en el diagnóstico y tratamiento. MATERIAL Y MÉTODOS: Todo paciente COVID-19 que ha ingresado con sintomatología neurológica o diagnosticado de encefalitis desde Marzo de 2020 en un hospital de tercer nivel en Zaragoza, España. RESULTADOS: Dos pacientes con infección COVID-19 confirmada por PCR nasofaríngea y cuyo cuadro clínico consistía en alteraciones neurológicas compatibles con encefalitis. La microbiología del líquido cefalorraquídeo (LCR) fue negativa para bacterias y virus, incluido el SARS-CoV-2 pero, ante la sospecha clínica de encefalitis por este último, se instauró tratamiento antiviral, con inmunoglobulinas y plasmaféresis de forma precoz. A pesar de ello la evolución no fue satisfactoria. CONCLUSIONES: La encefalitis por COVID-19 es una entidad clínica descrita recientemente, cuya fisiopatología aún se desconoce y no se dispone, hasta la fecha, de un tratamiento con evidencia clínica.

[Encephalitis as a neurological manifestation of COVID-19]. / Encefalitis como manifestación neurológica del COVID-19.

INTRODUCTION: In the context of the global COVID-19 pandemic, the different clinical manifestations of this infection pose a challenge for healthcare professionals. Respiratory involvement, the main symptom of SARS-CoV-2 infection, means that other manifestations, such as neurological, take a back seat, with the consequent delay in diagnosis and treatment. MATERIAL AND METHODS: All COVID-19 patients admitted with neurological symptoms or diagnosed with encephalitis since March 2020 in a tertiary hospital in Zaragoza, Spain. RESULTS: Two patients with COVID-19 infection confirmed by nasopharyngeal PCR and whose clinical picture consisted of neurological alterations compatible with encephalitis. Cerebrospinal fluid (CSF) microbiology was negative for bacteria and viruses, including SARS-CoV-2 but, given the clinical suspicion of encephalitis due to the latter, antiviral treatment with immunoglobulins and plasmapheresis was started early. Despite this, the evolution was not satisfactory. CONCLUSIONS: COVID-19 encephalitis is a recently described clinical entity, whose pathophysiology is still unknown and no treatment with clinical evidence is available to date.

Graft Risk Index After Liver Transplant: Internal and External Validation of a New Spanish Indicator.

OBJECTIVES: Scarcity of liver grafts has led to the use of marginal donors, consequently increasing the number of complications posttransplant. To prevent this situation, several indicators have been developed. However, important differences remain among countries. Here, we compared an early-risk liver transplant indicator based on the Spanish Liver Transplant Registry, called the Graft Risk Index, versus the US donor risk index and the Eurotransplant donor risk index. MATERIALS AND METHODS: The new indicator was based on prospectively collected data from 600 adult liver transplants performed in our center. We considered 2 events to compare the indexes: graft survival and rejection-free graft survival, with Cox proportional regression for analyses. Power to predict graft survival was evaluated by calculating the receiver operating characteristic area under the curve. RESULTS: We found no differences between the US and Eurotransplant donor risk indexes in prediction of patients with and without early graft failure. With regard to early survival, only the Graft Risk Index allowed better survival discrimination, in which survival progressively decreased with values ≥ 3 (with probability of graft survival at 1 month of 68%; 95% confidence interval, 46.2-82.5). This increase in risk was significant compared with the standard group (hazard ratio of 10.15; 95% confidence interval, C 3.91- 26.32; P < .001). We calculated powers of prediction of 0.52 (95% confidence interval, 0.43-0.62), 0.54 (95% confidence interval, 0.45-0.65), and 0.69 (95% confidence interval, 0.61-0.77) for donor risk index, Eurotransplant donor risk index, and early Graft Risk Index, respectively. CONCLUSIONS: Neither the US donor risk index nor the Eurotransplant donor risk index was valid for our Spanish liver donation and transplant program. Therefore, an indicator to predict posttransplant graft survival that is adapted to our environment is necessary. This national Graft Risk Index can be a useful tool to optimize donor-recipient matching.

Supervivencia del injerto tras trasplante hepático: aproximación a un nuevo índice de riesgo español / Graft survival after liver transplantation: an approach to a new Spanish risk index

Introducción: existen diversos indicadores para la valoración de la supervivencia del injerto hepático (DRI americano y ET-DRI europeo, entre otros), pero existen diferencias importantes entre los programas de trasplante de los diferentes países y podría ser que dichos indicadores no sean válidos en nuestro medio. Objetivos: el objetivo de este estudio es describir un nuevo indicador nacional de riesgo del injerto hepático a partir de los resultados del Registro Español de Trasplante Hepático (RETH) y validar el DRI y el ET-DRI. Metodología: el RETH incluye un análisis de Cox de los factores relacionados con la supervivencia del injerto. En base a sus resultados se define el indicador graft risk index (GRI). Las variables que contempla dependen del proceso de donación: edad, causa de muerte, compatibilidad sanguínea y tiempo de isquemia fría; y del receptor: edad, enfermedad de base, virus C, número de trasplante, estado UNOS y técnica quirúrgica. Se obtuvo la curva de la regresión logística y se calcularon las curvas de supervivencia del injerto por estratificación. La precisión se evaluó mediante el área ROC. Resultados: un GRI de 1 se corresponde con una probabilidad de pérdida del injerto del 23,25%; cada punto de aumento del GRI supone que la probabilidad se multiplica por 1,33. El GRI mostró la mejor discriminación por estratificación. El área ROC del DRI fue 0,54 (95% IC, 0,50-0,59) y del ET-DRI, 0,56 (95% IC, 0,51-0,61), frente al GRI 0,70 (95% IC, 0,65-0,73) (p < 0,0001). Conclusiones: el DRI y el ET-DRI no parecen útiles en nuestro medio y sería necesario disponer de un indicador propio. El GRI requiere un estudio nacional que perfile más el indicador y realice una validación más amplia

Introduction: several indicators are available to assess liver graft survival, including the American DRI and the European ET-DRI. However, there are significant differences between transplant programs of different countries, and the previously mentioned indicators might be not valid in our setting. Objectives: the aim of the study was to describe a new national liver graft risk indicator based on the results obtained from the Registro Español de Trasplante Hepático (RETH) and to validate the DRI and ET-DRI indicators. Methods: the RETH includes a Cox analysis of factors associated with graft survival; the graft risk index (GRI) indicator was defined based on these results. The variables considered are dependent upon the donation conditions (age, cause of death, blood compatibility and cold ischemia time) and the transplant recipient (age, underlying disease, hepatitis C virus, transplant number, UNOS status and surgical technique). A logistic regression curve was obtained and graft survival curves were calculated by stratification. Precision was assessed using the ROC analysis. Results: a GRI of 1 represents a probability of graft loss of 23.25%; each point increase in the GRI score multiplies this probability by 1.33. The best discrimination of GRI was obtained by stratification. The DRI ROC area was 0.54 (95% CI, 0.50-0.59) and the ET-DRI ROC area was 0.56 (95% CI, 0.51-0.61), compared to 0.70 (95% CI, 0.65-0.73) (p < 0.0001) for the GRI. Conclusions: both the DRI and ET-DRI do not seem to be useful in our setting. Hence a national indicator is more desirable. The GRI requires a national study in order to further streamline and assess this indicator

Graft survival after liver transplantation: an approach to a new Spanish risk index.

INTRODUCTION: several indicators are available to assess liver graft survival, including the American DRI and the European ET-DRI. However, there are significant differences between transplant programs of different countries, and the previously mentioned indicators might be not valid in our setting. OBJECTIVES: the aim of the study was to describe a new national liver graft risk indicator based on the results obtained from the Registro Español de Trasplante Hepático (RETH) and to validate the DRI and ET-DRI indicators. METHODS: the RETH includes a Cox analysis of factors associated with graft survival; the graft risk index (GRI) indicator was defined based on these results. The variables considered are dependent upon the donation conditions (age, cause of death, blood compatibility and cold ischemia time) and the transplant recipient (age, underlying disease, hepatitis C virus, transplant number, UNOS status and surgical technique). A logistic regression curve was obtained and graft survival curves were calculated by stratification. Precision was assessed using the ROC analysis. RESULTS: a GRI of 1 represents a probability of graft loss of 23.25%; each point increase in the GRI score multiplies this probability by 1.33. The best discrimination of GRI was obtained by stratification. The DRI ROC area was 0.54 (95% CI, 0.50-0.59) and the ET-DRI ROC area was 0.56 (95% CI, 0.51-0.61), compared to 0.70 (95% CI, 0.65-0.73) (p < 0.0001) for the GRI. CONCLUSIONS: both the DRI and ET-DRI do not seem to be useful in our setting. Hence a national indicator is more desirable. The GRI requires a national study in order to further streamline and assess this indicator.