Development and validation of the Gender-Equity Model for Liver Allocation (GEMA) to prioritise candidates for liver transplantation: a cohort study.

BACKGROUND: The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. METHODS: In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010-20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998-2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessed by Harrell's concordance statistic. FINDINGS: 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell's concordance statistic 0·752 [95% CI 0·700-0·804] vs 0·712 [0·656-0·769]; p=0·001 in the internal validation group and 0·761 [0·703-0·819] vs 0·739 [0·682-0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715-0·818] vs 0·742 [0·686-0·797]; p=0·0058 in the internal validation group and 0·774 [0·720-0·827] vs 0·745 [0·690-0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716-0·888]) and external validation cohorts (0·796 [0·698-0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. INTERPRETATION: GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation. FUNDING: Junta de Andalucía and EDRF.

COVID-19 contagion forecasting framework based on curve decomposition and evolutionary artificial neural networks: A case study in Andalusia, Spain.

Many types of research have been carried out with the aim of combating the COVID-19 pandemic since the first outbreak was detected in Wuhan, China. Anticipating the evolution of an outbreak helps to devise suitable economic, social and health care strategies to mitigate the effects of the virus. For this reason, predicting the SARS-CoV-2 transmission rate has become one of the most important and challenging problems of the past months. In this paper, we apply a two-stage mid and long-term forecasting framework to the epidemic situation in eight districts of Andalusia, Spain. First, an analytical procedure is performed iteratively to fit polynomial curves to the cumulative curve of contagions. Then, the extracted information is used for estimating the parameters and structure of an evolutionary artificial neural network with hybrid architectures (i.e., with different basis functions for the hidden nodes) while considering single and simultaneous time horizon estimations. The results obtained demonstrate that including polynomial information extracted during the training stage significantly improves the mid- and long-term estimations in seven of the eight considered districts. The increase in average accuracy (for the joint mid- and long-term horizon forecasts) is 37.61% and 35.53% when considering the single and simultaneous forecast approaches, respectively.

Cumulative exposure to tacrolimus and incidence of cancer after liver transplantation.

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case-control nested study aimed to evaluate the effect of maintenance immunosuppression on post-LT malignancy. The eligible cohort included 2495 LT patients who received tacrolimus-based immunosuppression. After 13 922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease, and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR = 1.06 [95% CI 1.05-1.07]; p < .001), male sex (HR = 1.50 [95% CI 1.14-1.99]), smoking habit (HR = 1.96 [95% CI 1.42-2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19-1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT.

Estudios de medicina nuclear aplicados a patologías nefrourinarias / Studies applied to nuclear medicine pathology nephrourinary

El presente artículo es una revisión bibliográfica sobre los estudios aplicables por medio de la tecnología nuclear destacando su utilidad en los estudios gammagráficos renales. El renograma es un procedimiento que utiliza radiosótopos nefrourológicos, con la generación de curvas actividad/tiempo, para el registro, adquisición de imágenes secuenciales dinámicas del riñón y consecuentemente el análisis cualitativo y cuantitativo de la información. El propósito del presente artículo es destacar la importancia de los estudios de Medicina Nuclear aplicados a patologías Nefrourinarias. La utilidad de este procedimiento es diversa permitiendo, la identificación de alteraciones a nivel morfológico, perfusorio, funcional y excretor renal. De igual manera este tipo de procedimientos son aplicables en la evaluación de las infecciones del tracto urinario, transplante renal, función renal, detección precoz de las posibles complicaciones; estudio de la progresión de la nefropatía crónica del injerto, valoración de la respuesta al tratamiento de las crisis de rechazo, monitorización en el tratamiento y/o recuperación quirúrgica, entre otras que se mencionan a continuación detalladamente.

This article is a literature review of the applicable studies using nuclear technology highlighting its usefulness in renal scintigraphy studies. The renal scan is a method using radioisotope nephro-urological, generating curves activity/time for recording, dynamic sequential acquisition of images of the kidney and consequently the qualitative and quantitative analysis of the information. The purpose of this article is to highlight the importance of Nuclear Medicine studies applied to pathologies nephrourinary. The usefulness of this procedure is diverse allowing the identification of functional morphological alterations, perfusorio, and renal excretory. Similarly these procedures are applicable in the evaluation of urinary tract infections, kidney transplant, renal function, early detection of possible complications; study the progression of chronic allograft nephropathy, evaluation of response to treatment of rejection crises, monitoring treatment and / or surgical recovery, among others mentioned below in detail.

Biopsias estereotáxicas: resultados en el manejo de gliomas de alto grado en el Hospital Carlos Van Buren 2000-2007 / Stereotactic biopsies: results in the management of high-grade gliomas in the Hospital Carlos Van Buren

Con el objetivo de comparar dos grupos similares de pacientes portadores de gliomas de alto grado diagnòsticados uno vìa estereotáxica y otro vía craneotomía, se diseño un estudio retrospectivo entre los años 2000 y 2007, con un diseño de casos y controles en el Hospital Carlos Van Buren de Valparaíso; los casos fueron los pacientes portadores de glioma de alto grado diagnósticado vía estereotáxica, los controles fueron pacientes similares pero diagnósticados vía biopsia quirúrgica convencional. Se recolectaron los datos de 19 pacientes biopsiados estereotáxicamente y de 15 enfermos biopsiados por craneotomía, no encontrándose diferencias significativas en cuanto a sexo, edad y localización tumoral entre ambos grupos, tampoco se encontraron diferencias significativas entre el Karnosfky performance status de ingreso y egreso hospitalario, las complicaciones y la mortalidad entre ambos grupos. La estadía hospitalaria postprocedimiento fue significativamente menor en el grupo biopsiado estereotáxicamente (p=0,0254). La mediana del costo fue en el caso de la estereotaxia de $444.070 pesos chilenos (U$925) y de $990.480 pesos chilenos (US2063) en el caso de las biopsias por craneotomía. Se aprecio una mayor sobrevida a dos años y medio en el grupo biopsiado por estereotáxia (p=0,169) . La obtención de una biopsia mediante estereotaxia no demostró asociarse a mayores complicaciones, morbilidad o mortalidad respecto a la biopsia tradicional, en el presente estudio. Asociándose a una menor estadía postprocedimiento, menores costos y una mayor sobrevida a dos años y medio, lo que hace altamente recomendable la realización de este tipo de técnica en pacientes que se sospeche la presencia de un glioma de alto grado.

Espectroscopia por RMN: una herramienta útil en el diagnóstico de tumores del sistema nervioso central / Magnetic resonance spectroscopy: an useful tool in the central nervous system tumors diagnostic

La espectroscopia analiza los protones que se encuentran en el cerebro, en condiciones normales y patológicas. El estudio de protones mediante espectroscopia tiene la ventaja de no utilizar sustancias radioactivas ya que los protones naturales son muy sensibles al alto rango giromagnético. El estudio se puede realizar en dos modalidades univoxel o multivoxel, difiriendo en el volumen del área a estudiar. Los metabolitos a estudiar son: N-acetil aspartato, colina, creatinina, lactato, mionositol, glutamato, y alanita. La espectroscopia es una herramienta útil en el diagnóstico de diferentes lesiones neurológicas como: infarto, tumores cerebrales, enfermedades metabólicas, encefalopatía hepática, demencia, epilepsia entre otras.