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Journal of Endocrinological... Jan 2017Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. The diagnostic criteria include two out of three features:... (Review)
Review
Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. The diagnostic criteria include two out of three features: hyperandrogenism, polycystic ovaries on ultrasound and menstrual irregularities (Rotterdam Criteria 2003). PCOS patients are more vulnerable to develop diabetes, cardiovascular diseases and metabolic syndrome. Insulin resistance (IR) is prevalent in women with PCOS independently of obesity and is critically involved in reproductive and metabolic complications of the syndrome. Several tests have been developed to measure IR, some very reliable but complex like the hyperinsulinemic euglycemic glucose clamp and others less precise but easier and less invasive like HOMA-IR. New markers are needed to reach a more reliable assessment of insulin resistance. To date, several surrogate markers have been proposed in the literature to facilitate and improve the determination of IR. Many new proteins are strongly involved with PCOS physiopathology and IR, such as some adipocytokines (adiponectin, visfatin, vaspin and apelin), copeptin, irisin, PAI-1 and zonulin. Many other proteins have been proposed as potential new markers of IR in PCOS, such as resistin, leptin, RBP4, kisspetin and ghrelin, but their role is still controversial. In this review, we provide a short characterization of these new markers, recently studied as indicators of metabolic state.
Topics: Biomarkers; Female; Humans; Insulin Resistance; Polycystic Ovary Syndrome
PubMed: 27473078
DOI: 10.1007/s40618-016-0523-8 -
Diabetes Research and Clinical Practice Oct 2018Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change, with close attention to known cardiovascular risk factors.
Topics: Biomarkers; Cardiovascular Diseases; Carotid Intima-Media Thickness; Disease Progression; Humans; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 30170074
DOI: 10.1016/j.diabres.2018.08.011 -
Future Oncology (London, England) Oct 2016Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face... (Review)
Review
Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility.
Topics: Aging; Antineoplastic Agents; Biomarkers; Female; Fertility; Fertility Preservation; Humans; Infertility, Female; Neoplasms; Ovarian Follicle; Ovarian Reserve; Ovary; Risk
PubMed: 27402553
DOI: 10.2217/fon-2016-0176 -
JNCI Cancer Spectrum Feb 2021Use of immunohistochemistry-based surrogates of molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Use of immunohistochemistry-based surrogates of molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative validity and prognostic capacity is scarce.
METHODS
Data from 2 PAM50-subtyped Swedish breast cancer cohorts were used: Stockholm tamoxifen trial-3 with 561 patients diagnosed 1976-1990 and Clinseq with 237 patients diagnosed 2005-2012. We evaluated 3 surrogate classifications; the immunohistochemistry-3 surrogate classifier based on estrogen receptor, progesterone receptor, and HER2 and the St. Gallen and Prolif surrogate classifiers also including Ki-67. Accuracy, kappa, sensitivity, and specificity were computed as compared with PAM50. Alluvial diagrams of misclassification patterns were plotted. Distant recurrence-free survival was assessed using Kaplan-Meier plots, and tamoxifen treatment benefit for luminal subtypes was modeled using flexible parametric survival models.
RESULTS
The concordance with PAM50 ranged from poor to moderate (kappa = 0.36-0.57, accuracy = 0.54-0.75), with best performance for the Prolif surrogate classification in both cohorts. Good concordance was only achieved when luminal subgroups were collapsed (kappa = 0.71-0.69, accuracy = 0.90-0.91). The St. Gallen surrogate classification misclassified luminal A into luminal B; the reverse pattern was seen with the others. In distant recurrence-free survival, surrogates were more similar to each other than PAM50. The difference in tamoxifen treatment benefit between luminal A and B for PAM50 was not replicated with any surrogate classifier.
CONCLUSIONS
All surrogate classifiers had limited ability to distinguish between PAM50 luminal A and B, but patterns of misclassifications differed. PAM50 subtyping appeared to yield larger separation of survival between luminal subtypes than any of the surrogate classifications.
Topics: Aged; Algorithms; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Breast Neoplasms; Cohort Studies; Female; Gene Expression; Genetic Markers; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Ki-67 Antigen; Middle Aged; Prognosis; Protein Array Analysis; ROC Curve; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Sensitivity and Specificity; Sequence Analysis, RNA; Sweden; Tamoxifen
PubMed: 33442660
DOI: 10.1093/jncics/pkaa087 -
Biometrics Dec 2019The development of methods to identify, validate, and use surrogate markers to test for a treatment effect has been an area of intense research interest given the...
The development of methods to identify, validate, and use surrogate markers to test for a treatment effect has been an area of intense research interest given the potential for valid surrogate markers to reduce the required costs and follow-up times of future studies. Several quantities and procedures have been proposed to assess the utility of a surrogate marker. However, few methods have been proposed to address how one might use the surrogate marker information to test for a treatment effect at an earlier time point, especially in settings where the primary outcome and the surrogate marker are subject to censoring. In this paper, we propose a novel test statistic to test for a treatment effect using surrogate marker information measured prior to the end of the study in a time-to-event outcome setting. We propose a robust nonparametric estimation procedure and propose inference procedures. In addition, we evaluate the power for the design of a future study based on surrogate marker information. We illustrate the proposed procedure and relative power of the proposed test compared to a test performed at the end of the study using simulation studies and an application to data from the Diabetes Prevention Program.
Topics: Biomarkers; Computer Simulation; Diabetes Mellitus; Humans; Models, Statistical; Statistics, Nonparametric; Time Factors; Treatment Outcome
PubMed: 31009073
DOI: 10.1111/biom.13067 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2022Low muscle mass is a common condition in the critically ill population and is associated with adverse clinical outcomes. The primary aim of this study was to analyze the...
INTRODUCTION
Low muscle mass is a common condition in the critically ill population and is associated with adverse clinical outcomes. The primary aim of this study was to analyze the prognostic significance of low muscle mass using computed tomography (CT) scans in COVID-19 critically ill patients. A second objective was to determine the accuracy and agreement in low muscle mass identification using diverse markers compared to CT as the gold standard.
METHODS
This was a prospective cohort study of COVID-19 critically ill patients. Skeletal muscle area at the third lumbar vertebra was measured. Clinical outcomes (intensive care unit [ICU] and hospital length of stay [LOS], tracheostomy, days on mechanical ventilation [MV], and in-hospital mortality) were assessed. Phase angle, estimated fat-free mass index, calf circumference, and mid-upper arm circumference were measured as surrogate markers of muscle mass.
RESULTS
Eighty-six patients were included (mean age ± SD: 48.6 ± 12.9; 74% males). Patients with low muscle mass (48%) had a higher rate of tracheostomy (50 vs 20%, p = 0.01), prolonged ICU (adjusted HR 0.53, 95%CI 0.30-0.92, p = 0.024) and hospital LOS (adjusted HR 0.50, 95% CI 0.29-0.86, p = 0.014). Bedside markers of muscle mass showed poor to fair agreement and accuracy compared to CT-assessed low muscle mass.
CONCLUSION
Low muscle mass at admission was associated with prolonged length of ICU and hospital stays. Further studies are needed to establish targeted nutritional interventions to halt and correct the catabolic impact of COVID-19 in critically ill patients, based on standardized and reliable measurements of body composition.
Topics: Male; Humans; Female; Critical Illness; Prognosis; COVID-19; Prospective Studies; Intensive Care Units; Length of Stay; Muscle, Skeletal; Biomarkers
PubMed: 35282986
DOI: 10.1016/j.clnu.2022.02.019 -
Journal of the Formosan Medical... Dec 2023Chronic hepatitis B virus (HBV) infection, which ultimately leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), remains a significant... (Review)
Review
Chronic hepatitis B virus (HBV) infection, which ultimately leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), remains a significant disease burden worldwide. Despite the use of antiviral therapy (AVT) using oral nucleos(t)ide analogs (NUCs) with high genetic barriers, the risk of HCC development cannot be completely eliminated. Therefore, bi-annual surveillance of HCC using abdominal ultrasonography with or without tumor markers is recommended for at-risk populations. For a more precise assessment of future HCC risk at the individual level, many HCC prediction models have been proposed in the era of potent AVT with promising results. It allows prognostication according to the risk of HCC development, for example, low-vs. intermediate-vs. high-risk groups. Most of these models have the advantage of high negative predictive values for HCC development, allowing exemption from biannual HCC screening. Recently, non-invasive surrogate markers for liver fibrosis, such as vibration-controlled transient elastography, have been introduced as integral components of the equations, providing better predictive performance in general. Furthermore, beyond the conventional statistical methods that primarily depend on multi-variable Cox regression analyses based on the previous literature, newer techniques using artificial intelligence have also been applied in the design of HCC prediction models. Here, we aimed to review the HCC risk prediction models that were developed in the era of potent AVT and validated among independent cohorts to address the clinical unmet needs, as well as comment on future direction to establish the individual HCC risk more precisely.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B virus; Hepatitis B, Chronic; Liver Neoplasms; Artificial Intelligence; Antiviral Agents; Liver Cirrhosis; Biomarkers, Tumor
PubMed: 37330305
DOI: 10.1016/j.jfma.2023.05.029 -
Mediation and instrumental variable analyses for vaccine-induced antibody titer against influenza B.Vaccine Apr 2023Immune correlate analyses for vaccine trials have been applied to investigate associations of vaccine efficacy and surrogate markers such as vaccine-induced antibodies....
OBJECTIVE
Immune correlate analyses for vaccine trials have been applied to investigate associations of vaccine efficacy and surrogate markers such as vaccine-induced antibodies. However, the role of antibody as a surrogate marker in predicting the outcome can vary by time, and surrogate-outcome confounding may have resulted in bias even in randomized trials. We provide a framework for surrogate marker assessment to address the aforementioned issues.
STUDY DESIGN AND SETTING
We reanalyzed the vaccine randomized trial for influenza B. We conducted a mediation analysis that enables estimation of vaccine efficacy, mediation effects and proportion of mediation on disease probabilities at various follow-up times. We proposed instrumental variable (IV) analyses with randomized vaccination as an IV accounting for potential unmeasured confounding.
RESULTS
The mediation effect of vaccine efficacy by hemagglutination inhibition (HAI) titer was significantly protective at 181 days after vaccination: 63.2% [95% confidence interval, (CI) = (39.9%, 82.0%)], and HAI titer explained 61.1% [95% CI = (36.7%, 96.2%)] of the protective effect of vaccination.
CONCLUSIONS
Most of vaccine efficacy is mediated by HAI titer, particularly in children 10 years and older. Our contribution is to provide causal analytics for the role of surrogate marker with weaker assumptions regarding surrogate-disease causation.
Topics: Child; Humans; Influenza, Human; Influenza Vaccines; Antibodies, Viral; Vaccination; Hemagglutination Inhibition Tests; Biomarkers
PubMed: 36925423
DOI: 10.1016/j.vaccine.2023.03.014 -
The Journal of the Association of... 2014Microbial translocation within the context of HIV disease has been described as one of the contributing causes of inflammation and disease progression in HIV infection.... (Review)
Review
Microbial translocation within the context of HIV disease has been described as one of the contributing causes of inflammation and disease progression in HIV infection. HIV-associated symptoms have been related to inflammatory markers and sCD14, a surrogate marker for microbial translocation, suggesting a plausible link between microbial translocation and symptom burden in HIV disease. Similar pathophysiological responses and symptoms have been reported in inflammatory bowel disease. We provide a comprehensive review of microbial translocation, HIV-associated symptoms, and symptoms connected with inflammation. We identify studies showing a relationship among inflammatory markers, sCD14, and symptoms reported in HIV disease. A conceptual framework and rationale to investigate the link between microbial translocation and symptoms is presented. The impact of inflammation on symptoms supports recommendations to reduce inflammation as part of HIV symptom management. Research in reducing microbial translocation-induced inflammation is limited, but needed, to further promote positive health outcomes among HIV-infected patients.
Topics: Bacterial Translocation; Biomarkers; CD4 Lymphocyte Count; Coinfection; HIV Infections; HIV-1; Humans; Inflammation
PubMed: 25305025
DOI: 10.1016/j.jana.2014.07.004 -
Breast Cancer Research and Treatment Sep 2023The purpose of this study was to investigate and classify the molecular subtypes of high-grade ductal carcinoma in situ (DCIS) and identify possible high-risk subtypes....
OBJECTIVE
The purpose of this study was to investigate and classify the molecular subtypes of high-grade ductal carcinoma in situ (DCIS) and identify possible high-risk subtypes. The heterogenicity of DCIS with variable clinical and histopathological presentations has been recognized. Nevertheless, only histopathological grading and diameter are currently implemented in clinical decision-making following the diagnosis of DCIS. The molecular subtypes of DCIS and their IHC surrogate markers have not been defined in conventional treatment guidelines and recommendations. We applied the definitions of molecular subtypes according to the IHC surrogate markers defined for IBC and subclassified high-grade DCIS, accordingly.
METHODS
Histopathological specimens were collected, revised, and regraded from 494 patients diagnosed with DCIS between 1996 and 2018. Other in situ and papillary lesions observed in breast biopsies were excluded from this study. 357 high-grade DCIS cases were submitted to IHC analysis. The markers investigated were ER, PR, HER2, and Ki67.
RESULTS
45 cases were classified as grade 1, 19 as grade 2, and 430 as grade 3. Sixty patients with high-grade DCIS had an additional invasive component in the surgical specimen. Thirty-three patients were diagnosed with recurrent DCIS or invasive cancer (minimum one year after their primary DCIS diagnosis). The proportions of luminal A and luminal B HER2-negative subtypes varied depending on whether 2011 or 2013 St. Gallen Consensus Conference guidelines were adopted. Luminal A was the most prevalent subtype, according to both classifications. The luminal B HER2-positive subtype was found in 22.1% of cases, HER2-enriched subtype in 21.8%, and TPN subtype in 5.6%. There were strong indications that HER2-enriched subtype was significantly more frequent among DCIS with invasive component (p = 0.0169).
CONCLUSIONS
High-grade DCIS exhibits all the molecular subtypes previously identified in IBC, but with a somewhat different distribution in our cohort. HER2-enriched subtype is substantially related to the presence of an invasive component in DCIS; consequently, it is regarded as a high-risk entity.
Topics: Humans; Female; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Incidence; Carcinoma, Ductal, Breast; Receptor, ErbB-2; Biomarkers, Tumor
PubMed: 37453021
DOI: 10.1007/s10549-023-07016-9