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Analisi comparativa tra le categorie diagnostiche di singolo centro e la casistica dell’European Liver Transplant Registry (ELTR).
Introduzione – L’European Liver Transplant Registry (ELTR), realizzato dall’European Liver Transplant Association, emanazione dell’European Society for Organ Transplantation (ESOT), rappresenta la base dati di maggiore complessità ed ampiezza disponibile a livello europeo inerente l’attività di trapianto di fegato. L’ELTR ha progressivamente attuato una raccolta dati che attualmente include 46530 trapianti di fegato effettuati su 41522 pazienti presso 124 Centri di 21 nazioni, per il periodo maggio 1968-dicembre 2001. Il Dipartimento Trapianti di Genova (DIT) contribuisce dal 1996 al registro ELTR.
Metodi – I dati del registro ELTR relativi all’attività di trapianto di fegato del periodo gennaio 1988-dicembre 2001 (44286 trapianti su 39196 pazienti) [1] sono stati analizzati in funzione delle indicazioni primarie al trapianto, attribuendo a ciascuna di queste (n=46) i codici diagnostici elaborati dalla stessa organizzazione [2]. Presso il DIT di Genova, nel periodo gennaio 2000-agosto 2003 sono stati effettuati 160 trapianti di fegato su 137 pazienti, individuando 15 diverse codifiche diagnostiche ELTR.
Risultati – Nello studio ELTR, la percentuale di sopravvivenza cumulativa ad un anno di organi e pazienti, comprendente l’insieme delle indicazioni, è risultata del 76% e dell’83%, rispettivamente. La casistica DIT ha rivelato una sopravvivenza cumulativa ad un anno di organi e pazienti del 72.99% e del 77.78%, rispettivamente. Il confronto tra la concordanza delle distribuzioni delle categorie diagnostiche ELTR e DIT rivela un modesto inter-rate agreement (Kappa di Cohen pesato: 0.325; regressione di Passing e Bablock: y = 0.15 + 6,58 x, P per deviazione dalla linearità 1% rispetto al complesso delle indicazioni DIT (A1-A4, B2, D1, D4, D5, D6, D7, E1), comprendenti l’88.26% ed il 53.2% delle casistiche DIT ed ELTR, rispettivamente, non è stata riscontrata alla regressione di Passing e Bablock alcuna deviazione significativa dalla linearità (y = -0,0024 + 0,4874 x; P >0.10). In particolare, la casistica DIT ha presentato una relativa prevalenza delle codifiche E1 (27% vs. 7%), D7 (2.18% vs. 0.2%), D5 (8.75% vs. 2%) e D4 (31.38% vs. 15%), mentre la casistica ELTR ha rivelato una prevalenza relativa nelle codifiche A1-A4 (2% vs. 1.45%) e D1 (18% vs. 14.59%). La sopravvivenza media ad un anno di organi e pazienti è così risultata per la casistica ELTR del 79.65% e dell’82.25%, contro l’81.38% e l’82.84% rispettivamente riscontrati nella casistica DIT.
Conclusioni – Il registro ELTR costituisce un importante riferimento per l’attività trapiantologica dei singoli Centri. Tuttavia, nel rapportare la casistica ELTR -di rilevante numerosità e assai diversificata territorialmente- alla casistica di un singolo Centro, è necessario utilizzare appropriati strumenti di confronto tra le categorie diagnostiche maggiormente rappresentate, al fine di limitare il rischio di comparazioni improprie sul piano metodologico e biased nei risultati e nelle relative interpretazioni.
Bibliografia - [1]. Adam R. et al. Evolution of liver transplantation in Europe: Report of the European Liver Transplant Registry. Liver Transplantation 9:1231-1243 (2003). [2]. http://www.eltr.or
Comparative analysis between diagnostic categories of a single-center vs. European Liver Transplant Registry (ELTR).
Introduction - The European Liver Transplant Registry (ELTR) currently represents the most widely dataset concerning liver transplantation (LT) activity available in Europe. The last ELTR report included 44,286 LT performed on 39,196 patients from January 1988 to December 2001 [1]. Our Department is
involved from 1996 in the ELTR data collection.
Methods - ELTR codes (n=46) were assigned to clinical diagnostic categories reported in the last ELTR analysis. In our Department, in the period January1, 2000 - August 31, 2003, 160 LT in 137 patients were performed. The patients were in 15 different ELTR diagnostic categories.
Results - In the ELTR analysis, 1-year patient survival (1yr-PtSurv) and 1-year graft survival (1yr-GrSurv) was 83% and 76%, respectively. In our series, 1yr-PtSurv and 1yr-GrSurv was 77.78% and 72.99%, respectively. Inter-rate agreement between ELTR vs. our Department ELTR diagnostic codes was poor (k = 0.325; Passing-Bablock regression, P<0.01). In our series, by considering only ELTR codes that were >1% with respect to the whole diagnostic categories (88.26% for our series, 53.2% with respect to ELTR series), no significance occurred in Passing-Bablock regression (P>0.10). Following this approach, in the ELTR series 1yr-PtSurv and 1yr-GrSurv was 82.25% and 79.65%, respectively, while in our series 1yr-PtSurv and 1yr-GrSurv was 82.84% and 81.38%, respectively.
Conclusions - The comparison between ELTR and single-center results required appropriate comparative procedures concerning patient diagnostic categories, in order to avoid the risk of a biased assessment about liver transplantation quality at the single-center level.
References - [1]. Adam R. et al. Liver Transplantation 9:1231-1243 (2003)
Comparative analysis between diagnostic categories of a single-center vs. European Liver Transplant Registry (ELTR).
Application of the RAND/UCLA appropriateness method to evaluate an informative system for liver transplantation in adult and pediatric recipients.
The Delphi Method (DM) is the most frequently used technique to acquire structured expert-opinion elicitation (EOE). It has been increasingly applied to construct guidelines in medicine and to evaluate the appropriateness of clinical procedures. In this study, the RAND/UCLA appropriateness method was used as a structured EOE process to evaluate the appropriateness of a dataset concerning liver transplantation in adult and pediatric recipients for an information system funded by the Italian Ministry of Health. The original dataset was obtained using an interdisciplinary pool of regional experts (n = 60). This dataset held 280 items stratified into three groups: I. pretransplant items (n = 123); II. transplant items (n = 65); III. early posttransplant and follow-up items (n = 92). In the second DM round, the dataset was subjected to an extraregional panel of independent experts (n = 9) to assess a score ranging from 1 to 9 on each item based on increasing appropriateness, according to the RAND/UCLA Appropriateness Method. Overall agreement, uncertainty, and disagreement between experts was 95.89%, 3.12%, and 0.99%, respectively. For each group, agreement-uncertainty-disagreement were 99.35%/0.65%/0% (group I), 91.53%/5.30%/3.17% (group II), and 96.87%/3.13%/0% (group III), respectively. This study supported the use of a structured EOE process to evaluate the appropriateness of a large dataset for liver transplantation activity
Application of a Bayesian simulation model to a database for split liver transplantation on two adult recipients in the environment of WinBUGS (Bayesian Inference Using Gibbs Sampling).
A Bayesian simulation model has been applied to a database developed for split liver transplantation on two adult recipients (SLT A/A) in the context of a macroregional project funded by the Italian Ministry of Health. The model was entered within Bayesian inference Using Gibbs Sampling (WinBUGS), a free software for Bayesian analysis of complex statistical models using Markov chain Monte Carlo techniques developed by the MRC Biostatistics Unit Cambridge jointly with the Imperial College School of Medicine at St Mary's, London. The model was built by using data entry performed from January 1, 2005 to August 5, 2005. In that period, 20 potential donors suitable for the SLT A/A procedure were entered into the database. We only selected the continuous and dichotomous donor-related variables (DRV, n = 62) for which almost one data entry procedure. The model assumed that a database user learned during data entry procedures for each donor, and that the probability of a successful input may depend on the number of previous errors and corrections. After binary transformation of the DRV (value 0 for each input record, value 1 for each no input record), we calculated an overall value of 0.28 +/- 0.27 (median: 0.3; 95% confidence interval: from 0.18 to 0.629). The transformed DRV were entered within the WinBUGS environment after model specification, assuming as success (y = 1) each procedure of input record, and as failure (y = 0) each procedure of no input record. A unequivocal convergence was obtained after 10,000 iterations, and a simulation run was launched for a further 10,000 updates. We obtained a negligible Monte Carlo error and a fine profile in the kernel density plot. This study supported the application of simulation models to databases concerning liver transplantation as a useful strategy to identify a critical state in the data entry process
Applicazione di un modello bayeseano di simulazione del profilo di completezza di una base dati di interesse trapiantologico nell’ambiente WinBUGS (Bayesian inference Using Gibbs Sampling).
Oggetto – Le informazioni relative ai donatori cadavere contenute in una base dati multicentrica compilata on-line durante il periodo 18/12/2004-05/08/2005 nell’ambito della fase di sperimentazione del Progetto “Strategie innovative per il trapianto di fegato (SITF): espansione del pool di organi adulti e pediatrici da donatore cadavere” sono state utilizzate per sviluppare un modello bayeseano di simulazione in merito alla completezza/appropriatezza del data entry.
Metodi – La base dati è stata trasformata in un insieme di variabili a codifica numerica binaria (0,1) mediante l’applicazione della funzione “IsMD(x) = 0” per i dati mancanti. La simulazione si è avvalsa di un’analisi originariamente condotta da Lindley circa la reazione di evitamento/apprendimento in un modello animale, assumendo per Y = 1 le risposte positive (successo) e per Y = 0 le risposte negative (fallimento), incorporando la probabilità di una risposta progressivamente migliorativa indotta dall’apprendimento per la probabilità di un fallimento. Nel presente studio è stata introdotta l’assunzione di indipendenza degli utilizzatori (Users, n = 20), considerando l’equivalente di ogni atto di data entry (n = 61 per singolo utilizzatore) ad un trial. Il modello è stato inserito e validato nell’ambiente WinBUGS (Bayesian inference Using Gibbs Sampling) secondo l’appropriata sintassi.
Risultati – La trasformazione della base dati mediante la funzione “IsMD(x) = 0” per i dati mancanti ha generato un valore medio di 0.72+/-0.73. Un ciclo di 10000 update in WinBUGS (CPU: 1400MHz; RAM: 128MB) ha conseguito il raggiungimento della convergenza con adeguata kernel density estimation. Il nodo “Users” ha restituito il valore di 0.9338+/-0.0025 (MC error: 2.704-5), mentre il nodo “Trials” ha restituito il valore di 0.9992+/-0.0000546 (MC error: 6.908-6).
Conclusioni – Il software WinBUGS costituisce un ambiente utile allo sviluppo di modelli di simulazione inerenti il profilo di completezza delle procedure di data entry in basi dati di interesse trapiantologico.
Bibliografia - 1. Santori G. et al. Transplant Proc 37:2415-2416 (2005). 2. Spiegelhalter D. et al. Dogs: loglinear model for binary data. In: BUGS Examples vol 1. WinBUGS User Manual. Version 1.4. January 2003. Imperial College & MRC, UK
Analisi mediante reti neurali dei fattori di rischio del donatore cadavere in relazione alla sopravvivenza dei pazienti sottoposti a trapianto di fegato.
INTRODUZIONE - Una rete neurale (RN) costituisce un insieme di processori elementari ("neuroni") collegati tra loro secondo una specifica matrice di connessione. La rete può analizzare un dato input per generare un output ("pattern recognition") approssimativamente coerente.
PAZIENTI E METODI - Sono stati considerati i donatori cadavere (DC, n=81) utilizzati per il prelievo di fegato nel periodo 2000-2001, attraverso la raccolta delle seguenti variabili continue (VDC): età (45.2+/-18.9; mediana: 44), BMI (23.8+/-4.7; 24.9), Bilirubina Tot (1.1+/-1.2; 0.7), ALT (68+/-220; 24), AST (65+/-124; 32), GGT (33+/-30; 23), PLT (153063+/-113285; 137000), PT (73+/-17; 75), APTT (42+/-15; 38), creatinina (1.4+/-1.5; 1.0), BUN (34+/-44; 21), Na+ (149.5+/-10.9; 148), K+ (3.9+/-0.8; 3.9). Le VDC e la variabile dicotomica maschio/femmina M/F (50/31) sono state assunte come variabili indipendenti, la tipologia di Tx [intero/split(SLT), 57/24] come variabile di subset e la sopravvivenza a sei mesi dal primo trapianto (Tx) come variabile dipendente. Sono stati testati con il software STATISTICA 6.1 i seguenti pattern: a) VDC (training: Tx fegato intero); b) VDC, escludendo l'età del DC; c) VDC (training: SLT); d) VDC, escludendo l'età del DC (training: SLT). Le RN testate erano di tipo lineare o multilayer (3-layer) perceptron (MLP), con apprendimento supervisionato mediante back-propagation. Una sola RN di tipo MPL è stata ritenuta per ogni pattern in base al regression ratio (RR) ed al train error (TE).
RISULTATI - Nel pattern a), l'architettura del MLP era 10:10-7-1:1 (RR:0.052688; TE:0.011869), mentre nel pattern b) l'architettura del MLP è risultata 11:11-8-1:1 (RR:0.0345; TE:0.0077). Nel pattern c), il MLP ha presentato una struttura 13:13-7-1:1 (RR:0.004294; TE:0.0016), mentre nel pattern d) l'architettura del MLP si è rivelata 11:11-7-1:1 (RR:0.0059; TE:0.0023).
CONCLUSIONI - La RN dove non era inserita l'età del DC ha presentato una migliore performance per il Tx di fegato intero, diversamente da quanto osservato per lo SLT
Effects of ischemia-reperfusion on hepatic glutathione and plasmatic markers of graft function during in situ split-liver transplantation in adult recipients.
In situ split-liver transplantation is a new surgical technique where the bipartition of a single liver allows procurement of a right graft (segments I, IV, V-VIII) for an adult recipient (75% of the total liver volume), and a left graft (segments II and III) for a child recipient. The present study was designed to assess the effects of ischemia-reperfusion on right grafts obtained by in situ split-liver transplantation. To this aim, hepatic glutathione and conventional plasmatic markers of allograft function (alanine and aspartate aminotransferase, total bilirubin, prothrombin time, lactate dehydrogenase, gamma-glutamyltranspeptidase, and alkaline phosphatase) were evaluated in four adult recipients. At the time of reperfusion, a marked glutathione decrease was found in the segment VI in three cases, whereas the amount of glutathione in segment IV was related to the duration of cold ischemia in all cases. Upon reperfusion, a marked increase in plasmatic alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase was found. A recovery in prothrombin time was observed from the first day in three cases. An increasing trend in total bilirubin, gamma-glutamyltranspeptidase, and alkaline phosphatase was noted from the second day after transplant. This preliminary study suggests a possible relationship between the duration of cold ischemia, amount of glutathione in segment IV of the right graft, and the trend in plasmatic markers of allograft damage during in situ split-liver transplantation in adult recipients.In situ split-liver transplantation is a new surgical technique where the bipartition of a single liver allows procurement of a right graft (segments I, IV, V-VIII) for an adult recipient (75% of the total liver volume), and a left graft (segments II and III) for a child recipient. The present study was designed to assess the effects of ischemia-reperfusion on right grafts obtained by in situ split-liver transplantation. To this aim, hepatic glutathione and conventional plasmatic markers of allograft function (alanine and aspartate aminotransferase, total bilirubin, prothrombin time, lactate dehydrogenase, γ-glutamyltranspeptidase, and alkaline phosphatase) were evaluated in four adult recipients. At the time of reperfusion, a marked glutathione decrease was found in the segment VI in three cases, whereas the amount of glutathione in segment IV was related to the duration of cold ischemia in all cases. Upon reperfusion, a marked increase in plasmatic alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase was found. A recovery in prothrombin time was observed from the first day in three cases. An increasing trend in total bilirubin, γ-glutamyltranspeptidase, and alkaline phosphatase was noted from the second day after transplant. This preliminary study suggests a possible relationship between the duration of cold ischemia, amount of glutathione in segment IV of the right graft, and the trend in plasmatic markers of allograft damage during in situ split-liver transplantation in adult recipients
Comparative analysis between MELD score vs. UNOS Status for predicting post-transplant mortality in liver recipients.
Introduction - The Model for End-Stage Liver Disease (MELD) score has replaced the conventional UNOS statuses 3/2B/2A to assess risk for mortality in patients awaiting liver transplantation (LT). However, further studies should be performed to evaluate the predictive value of the MELD score for posttransplant
mortality.
Patients and Methods - A group of adult patients that underwent a LT procedure in our Department during 01/01/2000-30/06/2004 period (n=140, M 100/F 40; age: 52.79±8.93) was enrolled as follows: i) classification in UNOS status 2A (n=13; 9.28%), 2B (n=123; 87.85%), or 3 (n=4; 2.85%); ii) no retransplantation;
3) full dataset about cadaveric donors (M 92/F 48; age: 49.17±19.25). For each patient was collected the last MELD calculated before LT. The patients were stratified for MELD score as follows: MELD 0-10, n=12; 11-18, n=61; 19-24, n=33; >25, n=34. Statistical analysis was performed by using Cohen’s k
for inter-rate agreement and c-statistic for Receiver Operating Characteristic (ROC) curves.
Results - A poor inter-rate agreement was found by Cohen’s k (k=0.048) in UNOS 2B patients for MELD score (MELD 0-10, n=10; 11-18, n=55; 19-24, n=30; >25, n=28). No significance occurred between MELD and UNOS ROC curves for patients mortality at 1 month (P=0.996), 3 months (P=0.714), 6 months (P=0.986), and 1 year (P=0.967).
Conclusions - In this study, no statistical differences was found between MELD score and conventional UNOS statuses in order to sensibility for posttransplant mortality in liver recipients
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