The proportion of Model for End-stage Liver Disease Sodium score attributable to creatinine independently predicts post-transplant survival and renal complications.
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ABSTRACT:
SUBMITTER: Bittermann T
PROVIDER: S-EPMC7092814 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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The proportion of Model for End-stage Liver Disease Sodium score attributable to creatinine independently predicts post-transplant survival and renal complications.
Bittermann Therese T Hubbard Rebecca A RA Lewis James D JD Goldberg David S DS
Clinical transplantation 20200220 3
The post-transplant outcomes of patients with Model for End-stage Liver Disease (MELD) score primarily driven by renal dysfunction are poorly understood. This was a retrospective cohort study of liver transplant (LT) alone recipients between 2005 and 2017 using the United Network for Organ Sharing (UNOS) database. The proportion of MELD Sodium score attributable to creatinine ("KidneyMELD") was calculated: (9.57 × ln (creatinine) × 100)/(MELD-Na - 6.43). The association of KidneyMELD with (a) al ...[more]
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Project description:BackgroundAlthough liver disease increases surgical risk, it is not considered in The Society for Thoracic Surgeons (STS) risk calculator. This study assessed the impact of Model for End-Stage Liver Disease (MELD) on outcomes after cardiac surgical procedures and the additional predictive value of MELD in the STS risk model.MethodsDeidentified records of 21,272 patients were extracted from a regional STS database. Inclusion criteria were any cardiac operation with a risk score available (2011-2016). Exclusion criteria included missing MELD (n = 2,895) or preoperative anticoagulation (n = 144). Patients were stratified into three categories, MELD < 9 (low), MELD 9 to 15 (moderate), and MELD > 15 (high). Univariate and multivariate logistic regression assessed risk-adjusted associations between MELD and operative outcomes.ResultsIncreasing MELD scores were associated with greater comorbid disease, mitral operation, prior cardiac operation, and higher STS-predicted risk of mortality (1.1%, 2.3%, and 6.0% by MELD category; p < 0.0001). The operative mortality rate increased with increasing MELD score (1.6%, 3.9%, and 8.4%; p < 0.0001). By logistic regression MELD score was an independent predictor of operative mortality (odds ratio, 1.03 per MELD score point; p < 0.0001) as were the components total bilirubin (odds ratio, 1.22 per mg/dL; p = 0.002) and international normalized ratio (odds ratio, 1.40 per unit; p < 0.0001). Finally, MELD score was independently associated with STS major morbidity and the component complications renal failure and stroke.ConclusionsIncreasing MELD score, international normalized ratio, and bilirubin all independently increase risk of operative mortality. Because high rates of missing data currently limit utilization of MELD, efforts to simplify and improve data collection would help improve future risk models.
| S-EPMC6541453 | biostudies-literature
Project description:ImportanceLiver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex.ObjectiveTo use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a sex adjustment.Design, setting, and participantsA retrospective cohort study was conducted from March 2019 to April 2020 to evaluate sex differences in laboratory values in liver transplant patients, patients with liver disease who did not undergo transplant, and healthy controls. Primary analyses were conducted in Vanderbilt University Medical Center (VUMC)'s deidentified electronic health record system. Replication analyses were conducted in the All of Us Research Program. Simulations of a sex-adjusted sodium-adjusted MELD (MELDNa) score were completed using liver transplant waiting list data from the liver simulated allocation modeling system. Patients who regularly used VUMC with measurements for any MELDNa component laboratory were included in the analyses. Analysis took place from November 2019 to March 2021.ExposuresElectronic health record-reported sex.Main outcomes and measureCreatinine, bilirubin, international normalized ratio, and sodium levels.ResultsThe VUMC sample was composed of 623 931 individuals (359 976 [57.7%] female) with a median (IQR) age of 44 (23-61) years. All component MELDNa laboratory values and calculated MELDNa scores yielded significant sex differences within VUMC (mean [SD] creatinine: male, 0.99 [0.39] mg/dL; female, 0.79 [0.30] mg/dL; P < .001; bilirubin: male, 0.76 [0.83] mg/dL; female, 0.58 [0.64] mg/dL; P < .001; international normalized ratio of prothrombin rate: male, 1.24 [0.42]; female, 1.20 [0.40]; P < .001; sodium: male, 139.00 [2.36] mEq/L; female, 139.03 [2.28] mEq/L; P < .001), resulting in MELDNa scoring that disadvantaged female individuals. This pattern persisted when the sample was divided into healthy controls, individuals with liver disease who did not undergo transplant, and patients who did undergo liver transplant. Female transplant patients had a greater number of decompensation traits (mean [SD]: male, 1.34 [1.11]; female, 1.60 [1.09]; P = .005), despite having lower MELDNa scores (mean [SD]: male, 21.72 [6.11]; female, 20.21 [6.15]; P = .005), indicating MELDNa scores are not accurately representing disease severity in female individuals. In simulations, the sex-adjusted MELDNa score modestly increased female transplant rate and decreased overall death.Conclusions and relevanceThese results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.
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Project description:BACKGROUND AND OBJECTIVE:Surgical complications after kidney transplantation can lead to catastrophic outcomes. Frailty has been associated with important kidney transplantation outcomes; however, there are no studies assessing this measure of physiological reserve as a specific predictor of surgical complications in this population. Such an assessment was, therefore, the objective of the present study. METHODS:A total of 87 individuals aged ? 18 years who underwent kidney transplantation between March 2017 and March 2018 were included. At the time of admission for kidney transplantation, demographic, clinical, and kidney transplantation data were collected, and the frailty score was calculated according to Fried et al., which comprises five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed. Urological, vascular, and general surgical complications were assessed three months later, or until graft loss or death. The propensity score was used to achieve a better homogeneity of the sample, and new analyses were performed in this new, balanced sample. RESULTS:Of the 87 individuals included, 30 (34.5%) had surgical complications. After propensity score matching, the risk of surgical complications was significantly higher among the frail individuals (RR 2.14; 95% CI 1.01-4.54; p = 0.035); specifically, the risk of noninfectious surgical complications was significantly higher among these individuals (RR 2.50; 95% CI 1.11-5.62; p = 0.017). CONCLUSION:The results showed that individuals with some degree of frailty before kidney transplantation were more subject to surgical complications. The calculation of the frailty score for transplant candidates and the implementations of measures to increase the physiological reserve of these patients at the time of kidney transplantation may possibly reduce the occurrence of surgical complications.
| S-EPMC7043931 | biostudies-literature
Project description:Sophisticated postoperative complications limit the long-term clinical success of liver transplantation. Hence, early identification of biomarkers is essential for graft and patient survival. High-throughput serum proteomics technologies provide an opportunity to identify diagnostic and prognostic biomarkers. This study is aimed to identify serum diagnosis biomarkers for complications and monitor effectiveness. Serum samples from 10 paired pre- and post-liver transplant patients, 10 acute rejection (AR) patients, 9 ischemic-type biliary lesion (ITBL) patients, and 10 healthy controls were screened using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to explore divergence in polypeptide. Then, we used ELISA and western blot analysis to validate the expression of these potential biomarkers, and studied the correlation of proteomic profiles with clinical parameters. ACLY, FGA, and APOA1 were significantly lower in pre-operative patients compared with healthy controls, and these patients had modest recovery after transplantation. Downregulation of both, ACLY and FGA, was also observed in AR and ITBL patients. Furthermore, bioinformatics analysis was performed and the results suggested that the identified proteins were involved in glucolipid metabolism and the clotting cascade. Together, these findings suggest that ACLY, FGA, and APOA1 could be novel non-invasive and early biomarkers to detect complications and predict effectiveness of liver transplantation.
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Project description:Hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with high-risk malignant and nonmalignant conditions. Nevertheless, various post-allogeneic HCT (allo-HCT) complications with diverse chronology, etiology, and pathophysiological background can develop, including general and organ-specific complications, such as graft dysfunction, infectious, and non-infectious etiologies, as well as non-infectious pulmonary complications (NIPCs). Post-transplant complications can also be related to conditioning intensity and drug-specific side effects. However, treatment options for these complications are suboptimal at present. Poor graft function (PGF) is a potentially life-threatening post-allo-HCT complication and is reported in 5-30% of patients. Nevertheless, consensus guidelines to define and treat PGF are not available. Most therapies are symptomatic with variable success rates. NIPCs are diverse and difficult to diagnose. The pathophysiology of NIPCs remains ill-defined, and effective treatment approaches have not been standardized, with mortality exceeding 50% for some conditions, such as idiopathic pneumonia syndrome (IPS). Modification of the conditioning regimen intensity and introduction of novel agents have been used to decrease post-allo-HCT complications, including infections, non-infectious complications, graft-versus-host disease (GvHD), as well as cardiopulmonary, neurological, hepatorenal, and other complications. Transplant-associated thrombotic microangiopathy (TA-TMA) is a lethal post-allo-HCT complication that may be associated with functional and genetic abnormalities in complement activation and related to the use of calcineurin inhibitors, such as cyclosporine and tacrolimus. The introduction of complement inhibitors has transformed TA-TMA from a lethal complication to a treatable syndrome.
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Project description:Background & aimsPrognostic models of cirrhosis underestimate disease severity for patients with cirrhosis and ascites. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein linked to hepatic neoangiogenesis and fibrogenesis. We investigated ascites MFAP4 as a predictor of transplant-free survival in patients with cirrhosis and ascites.MethodsA dual-centre observational study of patients with cirrhosis and ascites recruited consecutively in relation to a paracentesis was carried out. Patients were followed up for 1 year, until death or liver transplantation (LTx). Ascites MFAP4 was tested with the model for end-stage liver disease (MELD-Na), CLIF Consortium Acute Decompensation (CLIF-C AD), and Child-Pugh score in Cox regression models.ResultsNinety-three patients requiring paracentesis were included. Median ascites MFAP4 was 29.7 U/L [22.3-41.3], and MELD-Na was 19 [16-23]. A low MELD-Na score (<20) was observed in 49 patients (53%). During follow-up, 20 patients died (22%), and 6 received LTx (6%). High ascites MFAP4 (>29.7 U/L) was associated with 1-year transplant-free survival (p = 0.002). In Cox regression, ascites MFAP4 and MELD-Na independently predicted 1-year transplant-free survival (hazard ratio [HR] = 0.97, p = 0.03, and HR = 1.08, p = 0.01, respectively). Ascites MFAP4 and CLIF-C AD also predicted survival independently (HR = 0.96, p = 0.02, and HR = 1.05, p = 0.03, respectively), whereas only ascites MFAP4 did, controlling for the Child-Pugh score (HR = 0.97, p = 0.03, and HR = 1.18, p = 0.16, respectively). For patients with MELD-Na <20, ascites MFAP4 but not ascites protein predicted 1-year transplant-free survival (HR 0.91, p = 0.02, and HR = 0.94, p = 0.17, respectively).ConclusionsAscites MFAP4 predicts 1-year transplant-free survival in patients with cirrhosis and ascites. In patients with low MELD-Na scores, ascites MFAP4, but not total ascites protein, significantly predicted 1-year transplant-free survival.Lay summaryPatients with cirrhosis who have fluid in the abdomen, ascites, are at an increased risk of death and in need for liver transplantation. Our study identified patients with ascites and a poor prognosis by measuring microfibrillar associated protein 4 (MFAP4), a protein present in the abdominal fluid. Patients with low levels of the MFAP4 protein are at particularly increased risk of death or liver transplantation, suggesting that clinical care should be intensified in this group of patients.
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Project description:ImportanceMany established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown.ObjectiveTo determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women.Design, setting, and participantsCase-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18 437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184 309 women without breast cancer, with a total of 58 146 premenopausal and 144 600 postmenopausal women enrolled in the study.ExposuresBreast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (≥30 years vs <30 years).Main outcomes and measuresPopulation-attributable risk proportion of breast cancer.ResultsOf the 18 437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12 502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be averted if all women with heterogeneously or extremely dense breasts shifted to scattered fibroglandular breast density. Among postmenopausal women, 22.8% (95% CI, 18.3%-27.3%) of breast cancers could potentially be averted if all overweight and obese women attained a body mass index of less than 25.Conclusions and relevanceMost women with breast cancer have at least 1 breast cancer risk factor routinely documented at the time of mammography, and more than half of premenopausal and postmenopausal breast cancers are explained by these factors. These easily assessed risk factors should be incorporated into risk prediction models to stratify breast cancer risk and promote risk-based screening and targeted prevention efforts.
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Project description:Platelets are key mediators of atherothrombosis; yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. Here we derive and validate a Platelet Reactivity ExpreSsion Score (PRESS) integrating platelet aggregation responses and RNA sequencing in multiple cohorts. PRESS performs well in identifying a hyperreactive phenotype in patients with cardiovascular disease (AUC [cross-validation] 0.81, 95% CI 0.68 to 0.94), with similar discrimination in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 to 0.79); accuracy 80%, sensitivity 71%, and specificity 86%. Next, we validate PRESS in multiple cohorts of patients with platelet RNASeq available. Following multivariable adjustment, PRESS was significantly higher in MI (β=1.8, p=0.02), and individuals with a score above the median more frequently develop a future cardiovascular event (adjusted HR 1.90, CI 1.07 to 3.36), p=0.027). Altogether, we provide strong evidence that PRESS is a robust prognostic marker, which could have an essential role in facilitating a personalized approach to cardiovascular risk management.
2024-06-30 | GSE232027 | GEO
Project description:BackgroundAsthma is an inflammatory condition often punctuated by episodic symptomatic worsening, and accordingly, patients with asthma might have waxing and waning adherence to controller therapy.ObjectiveWe sought to measure changes in inhaled corticosteroid (ICS) adherence over time and to estimate the effect of this changing pattern of use on asthma exacerbations.MethodsICS adherence was estimated from electronic prescription and fill information for 298 participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity. For each patient, we calculated a moving average of ICS adherence for each day of follow-up. Asthma exacerbations were defined as the need for oral corticosteroids, an asthma-related emergency department visit, or an asthma-related hospitalization. Proportional hazard models were used to assess the relationship between ICS medication adherence and asthma exacerbations.ResultsAdherence to ICS medications began to increase before the first asthma exacerbation and continued afterward. Adherence was associated with a reduction in exacerbations but was only statistically significant among patients whose adherence was greater than 75% of the prescribed dose (hazard ratio, 0.61; 95% CI, 0.41-0.90) when compared with patients whose adherence was 25% or less. This pattern was largely confined to patients whose asthma was not well controlled initially. An estimated 24% of asthma exacerbations were attributable to ICS medication nonadherence.ConclusionsICS adherence varies in the time period leading up to and after an asthma exacerbation, and nonadherence likely contributes to a large number of these exacerbations. High levels of adherence are likely required to prevent these events.
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Project description:Sarcopenia is a prevalent condition that predicts prognosis in patients awaiting liver transplantation (LT). The gold standard for the diagnosis of sarcopenia is the assessment of the muscular area at L3 with computed tomography (CT) scan (skeletal muscle index [SMI]), but the routine use of CT scan is limited in clinical practice. Thus, we designed a single-center observational study aimed to evaluate the clinical factors associated with the presence of sarcopenia by SMI, and to build a score capable of predicting or excluding the presence of sarcopenia in patients on the LT waiting list (WL). Binary logistic regression analysis was performed to establish the factors independently associated with sarcopenia, and the Sarcopenia Hospital Italiano de Buenos Aires (HIBA) score was built from the resulting model after internal validation analysis by bootstrapping and correction for optimism. The predictive capability of mortality on the WL was evaluated with competing risk regression analysis. A total of 215 patients with cirrhosis on the LT WL were included. The independent factors associated with the presence of sarcopenia were male sex (odds ratio [OR]: 6.09, p < 0.001), body mass index (OR: 0.74, p < 0.001), Child Pugh (OR: 1.44, p < 0.001), and the ratio creatinine/Cystatin C (OR: 0.03, p = 0.007). The Sarcopenia HIBA score constructed with these variables showed an area under the curve of 0.862. During follow-up, 77 (36%) patients underwent LT, 46 (21%) died, and 92 (43%) remained alive. After adjusting for Model for End-Stage Liver Disease-Sodium, Sarcopenia HIBA score was an independent predictor of WL mortality (subhazard ratio: 1.19; 95% confidence interval 1.01-1.40; p = 0.042). Sarcopenia HIBA score is an easy-to-use, objective, and reliable diagnostic and predictive tool that can be useful to improve the prognostic evaluation and allow identifying a group of patients with a higher risk of death while awaiting LT.
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