Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1.

ABSTRACT:

Background

No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients.

Objective

The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis.

Methods

The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort.

Results

In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60-202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790-0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25-142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%-24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%-9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%-11.4%); C-statistic 0.744 [95% CI 0.644-0.844]).

Conclusions

A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated.

SUBMITTER: Biewenga M

PROVIDER: S-EPMC8281048 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Long-term overall survival and prognostic score predicting survival: the IMPACT study in precision medicine.

Project description:BACKGROUND:In 2007, we initiated IMPACT, a precision medicine program for patients referred for participation in early-phase clinical trials. We assessed the correlation of factors, including genomically matched therapy, with overall survival (OS). PATIENTS AND METHODS:We performed molecular profiling (Clinical Laboratory Improvement Amendments) (genes ≤ 182) for patients with lethal/refractory advanced cancers referred to the Phase 1 Clinical Trials Program. Matched therapy, if available, was selected on the basis of genomics. Clinical trials varied over time and included investigational drugs against various targets (single agents or combinations). Patients were followed up for up to 10 years. RESULTS:Of 3487 patients who underwent tumor molecular profiling, 1307 (37.5%) had ≥ 1 alteration and received therapy (matched, 711; unmatched, 596; median age, 57 years; 39% men). Most common tumors were gastrointestinal, gynecologic, breast, melanoma, and lung. Objective response rates were: matched 16.4%, unmatched 5.4% (p < .0001); objective response plus stable disease ≥ 6 months rates were: matched 35.3% and unmatched 20.3%, (p < .001). Respective median progression-free survival: 4.0 and 2.8 months (p < .0001); OS, 9.3 and 7.3 months; 3-year, 15% versus 7%; 10-year, 6% vs. 1% (p < .0001). Independent factors associated with shorter OS (multivariate analysis) were performance status > 1 (p < .001), liver metastases (p < .001), lactate dehydrogenase levels > upper limit of normal (p < .001), PI3K/AKT/mTOR pathway alterations (p < .001), and non-matched therapy (p < .001). The five independent factors predicting shorter OS were used to design a prognostic score. CONCLUSIONS:Matched targeted therapy was an independent factor predicting longer OS. A score to predict an individual patient's risk of death is proposed. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00851032, date of registration February 25, 2009.

| S-EPMC6937824 | biostudies-literature

Novel approaches for long-term lung transplant survival.

Project description:Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.

| S-EPMC9363671 | biostudies-literature

Prognostic Factors for Transplant-Free Survival and Validation of Prognostic Models in Chinese Patients with Primary Biliary Cholangitis Receiving Ursodeoxycholic Acid.

Project description:ObjectivesWe aimed to validate the prognostic models for primary biliary cholangitis (PBC) in Chinese patients receiving ursodeoxycholic acid (UCDA), and to compare their performances in predicting the long-term survival.MethodsChinese patients with PBC from a tertiary center were identified via electronic search of hospital medical registry. Risk factors associated with adverse events (liver transplantation or death from liver-related causes including hepatocellular carcinoma (HCC) and liver decompensation) were determined. Transplant-free survival was defined as survival free of liver-related death or transplantation.ResultsOf the 144 patients, 41 (28.5%) had baseline cirrhosis. The median age at diagnosis was 57.8 years. During a median follow-up of 7.0 years, 40 patients died (21 liver-related; 19 non-liver-related), 12 developed HCC, and 10 underwent transplantations. The 5-, 10-, and 15-year transplant-free survival probabilities were 91.0%, 78.1%, and 58.9%, respectively. Independent risk factors for adverse events were increasing age (hazard ratio (HR) 1.05), cirrhosis (HR 8.53), and suboptimal treatment response (HR 3.06). Aspartate aminotransferase/platelet ratio index at 1 year (APRI-r1) in combination with treatment response optimized the risk stratification. The performances of the GLOBE, UK-PBC scores, Rotterdam criteria, and APRI-r1 were comparable in predicting adverse events. The area under receiver operating curves within 5, 10, and 15 years were as follows-GLOBE score: 0.83, 0.85, and 0.85, respectively; UK-PBC score: 0.89, 0.83, and 0.79, respectively; Rotterdam criteria: 0.82, 0.76, and 0.80, respectively; APRI-r1: 0.80, 0.83, and 0.77, respectively.ConclusionsThe UK-PBC, GLOBE scores, Rotterdam criteria, and APRI-r1 had good and comparable prognostic prediction values for Chinese PBC patients receiving UCDA.

| S-EPMC5518946 | biostudies-literature

Glasgow prognostic score is a better predictor of the long-term survival in patients with gastric cancer, compared to the modified Glasgow prognostic score or high-sensitivity modified Glasgow prognostic score.

Project description:BackgroundInflammation influences cancer progression by increasing catabolism and impairing nutrient absorption. We compared the prognostic ability of three inflammation-based prognostic scoring systems-the Glasgow prognostic score (GPS), modified GPS (mGPS), and high-sensitivity mGPS (HS-mGPS)-in gastric cancer patients.Materials and methodsWe retrospectively examined 434 curatively resected gastric cancer patients to evaluate the prognostic ability of scoring systems for overall survival (OS) and cancer-specific survival (CSS).ResultsOS analysis identified the following independent prognostic factors: GPS model: pathological stage (pStage, p < 0.001), carcinoembryonic antigen (CEA, p = 0.004), and GPS 1 (hazard ratio [HR], 1.929; 95% confidence interval [CI], 1.152-3.228; p = 0.013); mGPS model: body mass index (BMI, p = 0.027), pStage (p < 0.001), and CEA (p < 0.001); HS-mGPS model: BMI (p = 0.029), pStage (p < 0.001), and CEA (p = 0.003). mGPS and HS-mGPS were not independent prognostic factors for OS. CSS analysis of the GPS model identified pStage (p < 0.001), CEA (p = 0.015), and GPS 1 (HR; 2.095, 95% CI; 1.025-4.283; p = 0.043) and 2 (HR, 2.812; 95% CI, 1.111-7.116; p = 0.029) as independent prognostic factors; however, mGPS and HS-mGPS were not independent prognostic factors for CSS. Log-rank tests demonstrated significant differences in OS among patients with GPS 0 vs. 1 (p < 0.001) and 0 vs. 2 (p < 0.001) and in CSS among the three GPS (0 vs. 1; p = 0.005, 0 vs. 2; p < 0.001, 1 vs. 2; p = 0.009).ConclusionsGPS most reliably predicts long-term survival of gastric cancer patients.

| S-EPMC7665228 | biostudies-literature

Long-term Patient and Graft Survival of Kidney Transplant Recipients With Hepatitis C Virus Infection in the United States.

Project description:BACKGROUND:Hepatitis C virus (HCV) infection is common among kidney transplant (KTx) recipients. However, the impact of HCV infection on long-term graft and recipient survival after KTx from large-scale data remains to be determined. METHODS:We used the Organ Procurement and Transplantation Network database to identify all adults undergoing KTx in 2004 to 2006 in the United States. A propensity score was created to match each HCV-positive recipient with an HCV-negative control for unbiased comparisons. Survival analysis was conducted to evaluate recipient and death-censored graft survival. RESULTS:Out of 33 357 adult primary KTx recipients, 1470 (4.4%) were HCV-positive: 1364 HCV-positive and -negative pairs were selected by propensity score matching. Based on multivariable regression models, HCV is associated with a higher risk of death (hazard ratio [HR], 1.50; 95% confidence interval [95% CI], 1.28-1.75) and graft failure (HR, 1.26; 95% CI, 1.08-1.47). Infection was a more common cause of death in HCV-positive patients than in HCV-negative recipients (HR, 1.64; 95% CI, 1.12-2.42). The incidence of death due to liver failure was 0.23% per year among HCV-positive recipients, whereas no HCV-negative recipients died from liver failure. Graft failure due to recurrent disease was higher in HCV-positive than in HCV-negative recipients (HR, 2.00; 95% CI, 1.06-3.78). CONCLUSION:HCV infection is associated with decreased long-term recipient and graft survival. Future studies are needed to examine whether recently available, safe, and effective antiviral therapy improves the long-term clinical outcome in these patients.

| S-EPMC5820195 | biostudies-literature

A prognostic score based on long-term survivor unique transcriptomic signatures predicts patient survival in pancreatic ductal adenocarcinoma.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis with few long-term survivors. This study aimed to establish a prognostic score using unique transcriptomic profiles of long-term survivors to be used as a patient selection tool for meaningful clinical intervention in PDAC. In TCGA PDAC cohort, 16 genes were significantly upregulated in the long-term survivor tumors. A prognostic score was established using these 16 genes by LASSO Cox regression, and PHKG1, HOXA4, ISL2, DMRT3 and TRA2A gene expressions were included in the score. The prognostic value was confirmed in both testing and validation cohorts. The characteristics of the high score tumor was investigated by bioinformatical approach. The high score tumor was associated with TP53 mutation but not with other commonly enhanced signaling pathways in PDAC. The high score tumor was associated with higher tumor mutational burden and unfavorable tumor microenvironment (TME), such as lower infiltration of CD8-positive T cells and dendritic cells, and less cell composition of mature blood vessels and fibroblasts. The high score tumor was also associated with enhanced cell proliferation and margin positivity after surgery. The impact of score component genes on the cell proliferation was investigated by in vitro experiments. Silencing of the score component genes promoted cell proliferation. In conclusion, the prognostic score predicted PDAC patient survival and was associated with cancer aggressiveness such as unfavorable TME and enhanced cell proliferation.

| S-EPMC8493373 | biostudies-literature

RDW-based clinical score to predict long-term survival in community-acquired pneumonia: a European derivation and validation study.

Project description:An excess long-term mortality has been observed in patients who were discharged after a community-acquired pneumonia (CAP), even after adjusting for age and comorbidities. We aimed to derive and validate a clinical score to predict long-term mortality in patients with CAP discharged from a general ward. In this retrospective observational study, we derived a clinical risk score from 315 CAP patients discharged from the Internal Medicine ward of Cuneo Hospital, Italy, in 2015-2016 (derivation cohort), which was validated in a cohort of 276 patients discharged from the pneumology service of the Barakaldo Hospital, Spain, from 2015 to 2017, and from two internal medicine wards at the Turin University and Cuneo Hospital, Italy, in 2017. The main outcome was the 18-month follow-up all-cause death. Cox multivariate analysis was used to identify the predictive variables and develop the clinical risk score in the derivation cohort, which we applied in the validation cohort. In the derivation cohort (median age: 79 years, 54% males, median CURB-65 = 2), 18-month mortality was 32%, and 18% in the validation cohort (median age 76 years, 55% males, median CURB-65 = 2). Cox multivariate analysis identified the red blood cell distribution width (RDW), temperature, altered mental status, and Charlson Comorbidity Index as independent predictors. The derived score showed good discrimination (c-index 0.76, 95% CI 0.70-0.81; and 0.83, 95% CI 0.78-0.87, in the derivation and validation cohort, respectively), and calibration. We derived and validated a simple clinical score including RDW, to predict long-term mortality in patients discharged for CAP from a general ward.

| S-EPMC7797708 | biostudies-literature

Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors.

Project description:Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ?60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ?60 years. In multivariate analysis, the donor type/age group and the graft CD34(+) and CD3(+) cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ?60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34(+) cell dose more than 4.5×10(6)/kg (HR: 0.56; P=0.002) and CD3(+) cell dose more than 3×10(8)/kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progression-free survival (P=0.04) but not for overall survival (P=0.82).

| S-EPMC3943316 | biostudies-literature

Risk score to predict event-free survival after hematopoietic cell transplant for sickle cell disease.

Project description:We developed a risk score to predict event-free survival (EFS) after allogeneic hematopoietic cell transplantation for sickle cell disease. The study population (n = 1425) was randomly split into training (n = 1070) and validation (n = 355) cohorts. Risk factors were identified and validated via Cox regression models. Two risk factors of 9 evaluated were predictive for EFS: age at transplantation and donor type. On the basis of the training cohort, patients age 12 years or younger with an HLA-matched sibling donor were at the lowest risk with a 3-year EFS of 92% (score, 0). Patients age 13 years or older with an HLA-matched sibling donor or age 12 years or younger with an HLA-matched unrelated donor were at intermediate risk (3-year EFS, 87%; score, 1). All other groups, including patients of any age with a haploidentical relative or HLA-mismatched unrelated donor and patients age 13 years or older with an HLA-matched unrelated donor were high risk (3-year EFS, 57%; score, 2 or 3). These findings were confirmed in the validation cohort. This simple risk score may guide patients with sickle cell disease and hematologists who are considering allogeneic transplantation as a curative treatment relative to other available contemporary treatments.

| S-EPMC7393258 | biostudies-literature

Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7.

Project description:Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation.We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well.P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival.

| S-EPMC3569513 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data