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Current Rheumatology Reports Aug 2017Patients with psoriasis and psoriatic arthritis, collectively termed psoriatic disease (PsD), are at an increased risk of developing cardiovascular diseases (CVD). The... (Review)
Review
PURPOSE OF REVIEW
Patients with psoriasis and psoriatic arthritis, collectively termed psoriatic disease (PsD), are at an increased risk of developing cardiovascular diseases (CVD). The purpose if this manuscript is to review recent evidence about the epidemiology and underlying mechanisms of CVD in psoriatic patients and approaches to improve the management of these comorbidities.
RECENT FINDINGS
Studies have shown that CVD risk is independent of traditional cardiovascular risk factors and is related to the systemic inflammatory nature of PsD. The use of surrogate markers, such as imaging of subclinical atherosclerosis, allows detection of patients at high cardiovascular risk before the occurrence of clinical events. These modalities could be clinically useful as clinical cardiovascular risk algorithms, such as the Framingham Risk Score, and have been shown to underestimate the actual cardiovascular risk in patients with PsD. Additional challenges related to the management of CVD in psoriatic patients include the underdiagnosis and undertreatment of traditional cardiovascular risk factors in rheumatology, dermatology and primary care setting. Effective measures used to control PsD, such as tumour necrosis factor inhibitors and methotrexate, has been associated with reduced cardiovascular risk in psoriatic patients. These findings highlight the importance of controlling disease activity as potential target that could lead to reduced cardiovascular risk. Together this highlights the importance of optimization of cardiovascular risk stratification and management of cardiovascular risk factors in patients with PsD.
Topics: Anti-Inflammatory Agents; Arthritis, Psoriatic; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Comorbidity; Humans; Inflammation; Psoriasis; Risk Assessment; Risk Factors
PubMed: 28844116
DOI: 10.1007/s11926-017-0692-2 -
Pediatric Nephrology (Berlin, Germany) Feb 2015At a recent meeting of international experts on clinical aspects of progressive chronic kidney disease (CKD), an extensive analysis of extant clinical trials was used to...
At a recent meeting of international experts on clinical aspects of progressive chronic kidney disease (CKD), an extensive analysis of extant clinical trials was used to develop more effective and economical surrogate markers for CKD outcomes in adults. This article describes the reasons for this undertaking, the methods and conclusions of the meeting, and the relevance of these findings to pediatric nephrology.
Topics: Adult; Biomarkers; Child; Disease Progression; Female; Glomerular Filtration Rate; Humans; Male; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 25370779
DOI: 10.1007/s00467-014-2995-0 -
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 -
Arteriosclerosis, Thrombosis, and... Feb 2016The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their... (Review)
Review
The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice.
Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Rupture; Biomarkers; Biomechanical Phenomena; Diagnostic Imaging; Dilatation, Pathologic; Disease Progression; Humans; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 26715680
DOI: 10.1161/ATVBAHA.115.306538 -
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 -
Therapeutische Umschau. Revue... Jan 2019Diagnosis and Monitoring of Inflammatory Bowel Disease Abstract. The diagnosis and monitoring of inflammatory bowel disease (IBD) is based on several factors: Clinical... (Review)
Review
Diagnosis and Monitoring of Inflammatory Bowel Disease Abstract. The diagnosis and monitoring of inflammatory bowel disease (IBD) is based on several factors: Clinical history, physical examination, laboratory values (blood and stool), endoscopy, histology and imaging. No single feature establishes the diagnosis alone. In recent years, therapeutic goals in IBD have evolved from clinical endpoints to endoscopic or even histologic targets. However, these targets, e. g. mucosal healing, still have to be uniformly defined. Repeated endoscopies are ill-tolerated by patients, therefore surrogate-markers of mucosal inflammation such as calprotectin, have been investigated and showed good correlation with endoscopic findings. In Crohn's Disease, directing therapy with tight control, based, among others, on fecal calprotectin, has been superior to conventional therapy-monitoring and decision making. However, these initial results need further confirmation. Therapeutic drug monitoring (TDM) has emerged as a second monitoring entity in the long term treatment of IBD patients. Especially with the increasing use of biologics, reactive TDM (in patients who relapse) and to a lesser extent proactive TDM (in patients who are in clinical remission / stable disease) have been studied and results have been adopted in current guidelines. Future studies will have to better define treatment targets and further investigate the impact of tight-monitoring on disease outcome.
Topics: Biomarkers; Crohn Disease; Feces; Humans; Inflammatory Bowel Diseases; Leukocyte L1 Antigen Complex; Remission Induction; Severity of Illness Index
PubMed: 30700246
DOI: 10.1024/0040-5930/a001002 -
Clinical Pharmacology and Therapeutics Aug 2018Cardiovascular diseases (CVD) are the first cause of death in the world. CVD risk is influenced by multiple factors, some nonmodifiable such as age, sex, and genetic... (Review)
Review
Cardiovascular diseases (CVD) are the first cause of death in the world. CVD risk is influenced by multiple factors, some nonmodifiable such as age, sex, and genetic background, and others modifiable. Great progress has been made over the last decades in the identification of biomarkers of incident or recurrent CV risk and surrogate endpoints of CV outcomes. We present the current state of knowledge for CV biomarkers in plasma including lipids, apolipoproteins, inflammation-related, and emerging omics-based biomarkers. Clinically validated surrogate endpoints for CV outcomes include plasma low-density lipoprotein-cholesterol reduction, and plasma triglyceride reduction is a likely relevant surrogate endpoint. High-density lipoprotein-cholesterol is not a validated surrogate endpoint, but is a useful biomarker of CV risk. CV risk biomarkers of interest include apolipoprotein B and non-HDL-cholesterol, lipoprotein (a), C-reactive protein, and recently, genetic and protein-based risk scores and gut microbiota-derived trimethylamine oxide levels.
Topics: Animals; Apolipoproteins; Biomarkers; Cardiovascular Diseases; Dyslipidemias; Gastrointestinal Microbiome; Genetic Markers; Humans; Inflammation; Inflammation Mediators; Lipids; Methylamines; Predictive Value of Tests; Prognosis; Risk Factors
PubMed: 29761474
DOI: 10.1002/cpt.1114 -
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 -
Nephrology, Dialysis, Transplantation :... Jan 2017Idiopathic membranous nephropathy (IMN) remains the most common cause of the nephrotic syndrome in adults and one of the leading identifiable causes of end-stage kidney... (Review)
Review
Idiopathic membranous nephropathy (IMN) remains the most common cause of the nephrotic syndrome in adults and one of the leading identifiable causes of end-stage kidney disease. Prior to considering the best approach to treatment, three important components need to be considered. First, the natural history of the typical membranous patient today; second, the importance of identifying the causative factors; and third, the integration of the current data on the known autoantibody/antigen systems involved in IMN into the diagnosis and management of the patient. Combining this with information on the known indicators associated with a poor prognosis plus new data on surrogate markers that provide important clues that the treatment plan is correct has provided us with a more secure platform for choosing the right treatment for each patient. This already provides a more rational and precise approach to the use of our current therapeutic options. Even today, we can slow disease progression and in the future new approaches and new therapies are likely to lead to prevention of progression or even reversal of the injury in IMN, thereby leading to improved quality of life of our patients.
Topics: Biomarkers; Disease Progression; Glomerulonephritis, Membranous; Humans
PubMed: 28391348
DOI: 10.1093/ndt/gfw404