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International Journal of Surgery... Oct 2020Hepatocellular carcinoma (HCC) is the liver's most common primary malignancy, with over half a million new cases diagnosed each year and being the fourth leading cause... (Review)
Review
Hepatocellular carcinoma (HCC) is the liver's most common primary malignancy, with over half a million new cases diagnosed each year and being the fourth leading cause of cancer death, worldwide. The poor prognosis of HCC is largely related to late diagnosis. Historically, serum alpha-fetoprotein and diagnostic imaging have been primary diagnostic modalities. However, the poor prognosis due to late diagnosis of HCC has proven unacceptable and, recently, significant efforts have been devoted to identifying patients with early stage HCC. Molecular biomarkers can provide additional and relevant information about the biological behavior of these tumors. Research in biomarker combinations may provide more accurate and valuable information for the future individualized HCC diagnosis and/or prognosis. Several biomarkers with prognostic significance have been identified, however all of them have been studied retrospectively. Furthermore, of all different molecular signatures that have been published, very few have been externally validated. The aim of this review is to analyze the most relevant emerging biomarkers of HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Predictive Value of Tests; Prognosis; Reference Values; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index
PubMed: 32344023
DOI: 10.1016/j.ijsu.2020.04.043 -
Current Atherosclerosis Reports Jun 2023Non-invasive measurements such as arterial stiffness serve as proxy surrogates for detection of early atherosclerosis and ASCVD risk stratification. These surrogate... (Review)
Review
PURPOSE OF REVIEW
Non-invasive measurements such as arterial stiffness serve as proxy surrogates for detection of early atherosclerosis and ASCVD risk stratification. These surrogate measurements are influenced by age, gender, and ethnicity and affected by the physiological changes of puberty and somatic growth in children and adolescents.
RECENT FINDINGS
There is no consensus of the ideal method to measure surrogate markers in youth (< 18 years of age), nor standardized imaging protocols for youth. Currently, pediatric normative data are available but not generalizable. In this review, we provide rationale on how currently used surrogates can help identify subclinical atherosclerosis in youth and affirm their role in identifying youth at risk for premature CVD.
Topics: Humans; Adolescent; Child; Cardiovascular Diseases; Carotid Arteries; Risk Factors; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; Vascular Stiffness
PubMed: 37148462
DOI: 10.1007/s11883-023-01101-6 -
Scandinavian Journal of Public Health Nov 2020Disparity in cardiovascular disease (CVD) mortality and risk factor levels between urban and rural regions has been confirmed worldwide. The aim of this study was to...
Disparity in cardiovascular disease (CVD) mortality and risk factor levels between urban and rural regions has been confirmed worldwide. The aim of this study was to examine how living in different community types (urban-rural) in childhood and adulthood are related to cardiovascular risk factors and surrogate markers of CVD such as carotid intima-media thickness (IMT) and left ventricular mass (LVM). The study population comprised 2903 participants (54.1% female, mean age 10.5 years in 1980) of the Cardiovascular Risk in Young Finns Study who had been clinically examined in 1980 (age 3-18 years) and had participated in at least one adult follow-up (2001-2011). In adulthood, urban residents had lower systolic blood pressure (-1 mmHg), LDL-cholesterol (-0.05 mmol/l), lower body mass index (-1.0 kg/m) and glycosylated haemoglobin levels (-0.05 mmol/mol), and lower prevalence of metabolic syndrome (19.9 v. 23.7%) than their rural counterparts. In addition, participants continuously living in urban areas had significantly lower IMT (-0.01 mm), LVM (1.59 g/m) and pulse wave velocity (-0.22 m/s) and higher carotid artery compliance (0.07%/10 mmHg) compared to persistently rural residents. The differences in surrogate markers of CVD were only partially attenuated when adjusted for cardiovascular risk factors.
Topics: Adult; Biomarkers; Cardiovascular Diseases; Carotid Intima-Media Thickness; Child; Female; Finland; Follow-Up Studies; Health Status Disparities; Heart Ventricles; Humans; Male; Middle Aged; Organ Size; Risk Factors; Rural Population; Urban Population
PubMed: 31464561
DOI: 10.1177/1403494819869816 -
Kidney360 Jun 2024AKI is a common and serious complication of cardiac surgery that has a significant impact on patient morbidity and mortality. The Kidney Disease Improving Global... (Review)
Review
AKI is a common and serious complication of cardiac surgery that has a significant impact on patient morbidity and mortality. The Kidney Disease Improving Global Outcomes definition of AKI is widely used to classify and identify AKI associated with cardiac surgery (cardiac surgery-associated AKI [CSA-AKI]) on the basis of changes in serum creatinine and/or urine output. There are various preoperative, intraoperative, and postoperative risk factors for the development of CSA-AKI which should be recognized and addressed as early as possible to expedite its diagnosis, reduce its occurrence, and prevent or ameliorate its devastating complications. Crucial issues are the inaccuracy of serum creatinine as a surrogate parameter of kidney function in the perioperative setting of cardiothoracic surgery and the necessity to discover more representative markers of the pathophysiology of AKI. However, except for the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 ratio, other diagnostic biomarkers with an acceptable sensitivity and specificity are still lacking. This article provides a comprehensive review of various aspects of CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, prevention, and treatment management.
Topics: Humans; Acute Kidney Injury; Cardiac Surgical Procedures; Risk Factors; Biomarkers; Postoperative Complications; Creatinine
PubMed: 38689404
DOI: 10.34067/KID.0000000000000466 -
Journal of Neural Transmission (Vienna,... Feb 2022The abnormal accumulation of α-synuclein in the brain is a common feature of Parkinson's disease (PD), PD dementia (PDD), dementia with Lewy bodies (DLB) and multiple... (Review)
Review
The abnormal accumulation of α-synuclein in the brain is a common feature of Parkinson's disease (PD), PD dementia (PDD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), and synucleinopathies that present with overlapping but distinct clinical symptoms that include motor and cognitive deficits. Synapse degeneration is the crucial neuropathological event in these synucleinopathies and the neuropathological correlate of connectome dysfunction. The cognitive and motor deficits resulting from the connectome dysfunction are currently measured by scalar systems that are limited in their sensitivity and largely subjective. Ideally, a marker of synapse degeneration would correlate with measures of cognitive or motor impairment, and could therefore be used as a more objective, surrogate biomarker of the core clinical features of these diseases. Furthermore, an objective surrogate biomarker that can detect and monitor the progression of synapse degeneration would improve patient management and clinical trial design, and could provide a measure of therapeutic response. Here, we review the published findings relating to candidate biomarkers of synapse degeneration in PD, PDD, DLB, and MSA patient-derived biofluids and discuss the findings in the context of the mechanisms associated with α-synuclein-mediated synapse degeneration. Understanding these mechanisms is essential not only for discovery of biomarkers, but also to improve our understanding of the earliest changes in disease pathogenesis of synucleinopathies.
Topics: Biomarkers; Humans; Lewy Body Disease; Multiple System Atrophy; Synapses; Synucleinopathies; alpha-Synuclein
PubMed: 35147800
DOI: 10.1007/s00702-022-02467-8 -
Biometrics Dec 2021The utilization of surrogate markers offers the opportunity to reduce the length of required follow-up time and/or costs of a randomized trial examining the...
The utilization of surrogate markers offers the opportunity to reduce the length of required follow-up time and/or costs of a randomized trial examining the effectiveness of an intervention or treatment. There are many available methods for evaluating the utility of a single surrogate marker including both parametric and nonparametric approaches. However, as the dimension of the surrogate marker increases, a completely nonparametric procedure becomes infeasible due to the curse of dimensionality. In this paper, we define a quantity to assess the value of multiple surrogate markers in a time-to-event outcome setting and propose a robust estimation approach for censored data. We focus on surrogate markers that are measured at some landmark time, t , which occurs earlier than the end of the study. Our approach is based on a dimension reduction procedure with an option to incorporate weights to guard against potential misspecification of the working model, resulting in three different proposed estimators, two of which can be shown to be double robust. We examine the finite sample performance of the estimators under various scenarios using a simulation study. We illustrate the estimation and inference procedures using data from the Diabetes Prevention Program (DPP) to examine multiple potential surrogate markers for diabetes.
Topics: Biomarkers; Causality; Computer Simulation; Diabetes Mellitus; Humans; Models, Statistical
PubMed: 32920821
DOI: 10.1111/biom.13370 -
Biometrics Jun 2021The use of surrogate markers to examine the effectiveness of a treatment has the potential to decrease study length and identify effective treatments more quickly. Most...
The use of surrogate markers to examine the effectiveness of a treatment has the potential to decrease study length and identify effective treatments more quickly. Most available methods to investigate the usefulness of a surrogate marker involve restrictive parametric assumptions and tend to focus on settings where the surrogate is measured at a single point in time. However, in many clinical settings, the potential surrogate marker is often measured repeatedly over time, and thus, the surrogate marker information is a trajectory of measurements. In addition, it is often difficult in practice to correctly specify the relationship between a treatment, primary outcome, and surrogate marker trajectory. In this paper, we propose a model-free definition for the proportion of the treatment effect on the primary outcome that is explained by the treatment effect on the longitudinal surrogate markers. We propose three novel flexible methods to estimate this proportion, develop the asymptotic properties of our estimators, and investigate the robustness of the estimators under multiple settings via a simulation study. We apply our proposed procedures to an AIDS clinical trial dataset to examine a trajectory of CD4 counts as a potential surrogate.
Topics: Biomarkers; Computer Simulation; Treatment Outcome
PubMed: 32506496
DOI: 10.1111/biom.13310 -
BioMed Research International 2021Several decades of improving dairy cattle towards unilateral utilization of dairy cattle led to enormous progress in the field of milk yield; however, it resulted in a... (Review)
Review
Several decades of improving dairy cattle towards unilateral utilization of dairy cattle led to enormous progress in the field of milk yield; however, it resulted in a number of unfavorable features, such as reproductive disorders, increased calf mortality, and reduced health. Most cases of embryo loss and/or lost pregnancies occur during the first four to five weeks of gestation; accurate detection for pregnancy during this period is likely to contribute to an improvement in gestation rates. A specific protein, interferon-tau (IFNT), stimulates interferon-stimulated genes (ISGs), and their expression increases during gestation within 21 days after insemination. In bovines, the early conceptus undergoes a phase of rapid growth and elongation before implantation, the latter occurring 2-3 weeks after fertilization. IFNT acts mainly in the endometrium of the luminal epithelium. It is a new type I interferon that regulates several genes encoding uterine-derived factors. They are crucial in the processes of preparing the uterus for placenta attachment, modifying the uterine immune system, and regulating early fetal development. Because IFNT is expressed and induces ISGs in the endometrium during pregnancy recognition, it was reasoned that surrogate markers for pregnancy or IFNT might be present in the blood and provide an indicator of pregnancy status in cattle.
Topics: Animals; Biomarkers; Cattle; Embryo, Mammalian; Endometrium; Epithelium; Female; Gene Expression; Gene Expression Regulation; Interferon Type I; Pregnancy; Pregnancy Proteins; Uterus
PubMed: 34513997
DOI: 10.1155/2021/9915814 -
Biostatistics (Oxford, England) Oct 2023When evaluating the effectiveness of a treatment, policy, or intervention, the desired measure of efficacy may be expensive to collect, not routinely available, or may... (Randomized Controlled Trial)
Randomized Controlled Trial
When evaluating the effectiveness of a treatment, policy, or intervention, the desired measure of efficacy may be expensive to collect, not routinely available, or may take a long time to occur. In these cases, it is sometimes possible to identify a surrogate outcome that can more easily, quickly, or cheaply capture the effect of interest. Theory and methods for evaluating the strength of surrogate markers have been well studied in the context of a single surrogate marker measured in the course of a randomized clinical study. However, methods are lacking for quantifying the utility of surrogate markers when the dimension of the surrogate grows. We propose a robust and efficient method for evaluating a set of surrogate markers that may be high-dimensional. Our method does not require treatment to be randomized and may be used in observational studies. Our approach draws on a connection between quantifying the utility of a surrogate marker and the most fundamental tools of causal inference-namely, methods for robust estimation of the average treatment effect. This connection facilitates the use of modern methods for estimating treatment effects, using machine learning to estimate nuisance functions and relaxing the dependence on model specification. We demonstrate that our proposed approach performs well, demonstrate connections between our approach and certain mediation effects, and illustrate it by evaluating whether gene expression can be used as a surrogate for immune activation in an Ebola study.
Topics: Humans; Models, Statistical; Biomarkers; Causality; Computer Simulation
PubMed: 35791753
DOI: 10.1093/biostatistics/kxac020 -
Journal of Gastroenterology and... Jan 2023Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease of unknown etiology, involving complex interactions between the gut microbiome and host immune... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease of unknown etiology, involving complex interactions between the gut microbiome and host immune response. The microbial dysbiosis is well documented in IBD and significantly influences the host metabolic pathways. Thus, a metabolomic fingerprint resulting from the influence of gut dysbiosis in IBD could aid in assessing the disease activity. PubMed, Medline, Science Direct, and Web of Science were searched for studies exploring the association between microbiome and metabolome in IBD patients in the last 5 years. Additionally, references of cited original articles and reviews were further assessed for relevant work. We provide a literature overview of the recent metabolomic studies performed on patients with IBD. The findings report alterations in the metabolite levels of these patients. We also discuss the gut dysbiosis observed in IBD and its influence on host metabolic pathways such as lipids, amino acids, short-chain fatty acids, and others. IBD, being a chronic idiopathic disease, requires routine monitoring. The available non-invasive markers have their limitations. The metabolite changes account for both dysbiosis and its influence on the host's immune response and metabolism. A metabolome approach would thus facilitate the identification of surrogate metabolite markers reflecting the disease activity.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Dysbiosis; Feces; Inflammatory Bowel Diseases; Metabolome; Gastrointestinal Microbiome; Biomarkers
PubMed: 36287112
DOI: 10.1111/jgh.16043