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Epilepsia Sep 2021Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency...
OBJECTIVE
Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency oscillations (HFOs), spikes, and cross-rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery.
METHODS
Interictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross-rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF-TC and to subsequent resective surgery.
RESULTS
After thermocoagulation, 19 patients showed a clinical improvement. At the individual level, clinically improved patients more frequently had a reduction in spikes and cross-rate in the epileptogenic zone than patients without clinical improvement (p = .002, p = .02). At a group level, there was a greater decrease of HFOs in epileptogenic and thermocoagulated zones in patients with clinical improvement (p < .05) compared to those with no clinical benefit. Eventually, a significant decrease of all the markers after RF-TC was found in patients with a favorable outcome of resective surgery (spikes, p = .026; HFOs, p = .03; cross-rate, p = .03).
SIGNIFICANCE
Quantified changes in the rate of spikes, rate of HFOs, and cross-rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF-TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF-TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery.
Topics: Biomarkers; Electrocoagulation; Electroencephalography; Humans; Imaging, Three-Dimensional; Seizures; Treatment Outcome
PubMed: 34272883
DOI: 10.1111/epi.16989 -
Clinical and Applied... 2023Preeclampsia (PE) is associated with endothelial injury and hemostatic abnormalities. However, the diagnostic role of coagulation parameters and natural anticoagulants...
Preeclampsia (PE) is associated with endothelial injury and hemostatic abnormalities. However, the diagnostic role of coagulation parameters and natural anticoagulants in predicting PE has not been explored in Ghana. This study assessed plasma levels of these factors as surrogate markers of PE and its subtypes. This case-control study included 90 women with PE (cases) and 90 normotensive pregnant women (controls). Blood samples were drawn for the estimation of complete blood count and coagulation tests. The prothrombin time (PT), activated partial thromboplastin time (APTT), and the calculation of the international normalized ratio (INR) were determined by an ACL elite coagulometer while the levels of protein C (PC), protein S (PS), antithrombin III (ATIII), and D-dimers were also measured using the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) method. All statistical analyses were performed using the R Language for Statistical Computing. Results showed significantly (< .05) shortened APTT (28.25 s) and higher D-dimer levels (1219.00 ng/mL) among PE women, as well as low levels of PC (1.02 µg/mL), PS (6.58 µg/mL), and ATIII (3.99 ng/mL). No significant difference was found in terms of PT and INR. From the receiver operating characteristic analysis, PC, PS, and ATIII could significantly predict PE and its subtypes at certain cutoffs with high accuracies (area under the curve [AUC] ≥0.70). Most women with PE are in a hypercoagulable state with lower natural anticoagulants. PC, PS, and ATIII are good predictive and diagnostic markers of PE and its subtypes (early-onset PE [EO-PE] and late-onset PE [LO-PE]) and should be explored in future studies.
Topics: Female; Humans; Pregnancy; Anticoagulants; Ghana; Pre-Eclampsia; Case-Control Studies; Blood Coagulation Factors; Protein C; Biomarkers
PubMed: 37787124
DOI: 10.1177/10760296231204604 -
The European Journal of Neuroscience Nov 2022A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a...
A biomarker associated with cognition in neurodegenerative dementias would aid in the early detection of disease progression, complement clinical staging and act as a surrogate endpoint in clinical trials. The current systematic review evaluates the association between cerebrospinal fluid protein markers of synapse loss and neuronal injury and cognition. We performed a systematic search which revealed 67 studies reporting an association between cerebrospinal fluid markers of interest and neuropsychological performance. Despite the substantial heterogeneity between studies, we found some evidence for an association between neurofilament-light and worse cognition in Alzheimer's diseases, frontotemporal dementia and typical cognitive ageing. Moreover, there was an association between cerebrospinal fluid neurogranin and cognition in those with an Alzheimer's-like cerebrospinal fluid biomarker profile. Some evidence was found for cerebrospinal fluid neuronal pentraxin-2 as a correlate of cognition across dementia syndromes. Due to the substantial heterogeneity of the field, no firm conclusions can be drawn from this review. Future research should focus on improving standardization and reporting as well as establishing the importance of novel markers such as neuronal pentraxin-2 and whether such markers can predict longitudinal cognitive decline.
Topics: Humans; Amyloid beta-Peptides; tau Proteins; Alzheimer Disease; Cognitive Dysfunction; Cognition; Biomarkers; Aging
PubMed: 35338546
DOI: 10.1111/ejn.15656 -
ACS Biomaterials Science & Engineering Jan 2024Cytokines are regulated in acute and chronic inflammation, including rheumatoid arthritis (RA) and myocardial infarction (MI). However, the dynamic windows within which... (Review)
Review
Cytokines are regulated in acute and chronic inflammation, including rheumatoid arthritis (RA) and myocardial infarction (MI). However, the dynamic windows within which cytokine activity/inhibition is desirable in RA and MI change timely and locally during the disease. Therefore, traditional, static delivery regimens are unlikely to meet the idiosyncrasy of these highly dynamic pathophysiological and individual processes. Responsive delivery systems and biomaterials, sensing surrogate markers of inflammation (i.e., matrix metalloproteinases - MMPs) and answering with drug release, may present drug activity at the right time, manner, and place. This article discusses MMPs as surrogate markers for disease activity in RA and MI to clock drug discharge to MMP concentration profiles from MMP-responsive drug delivery systems and biomaterials.
Topics: Humans; Cytokines; Matrix Metalloproteinases; Arthritis, Rheumatoid; Inflammation; Biomarkers; Biocompatible Materials
PubMed: 37102329
DOI: 10.1021/acsbiomaterials.2c01320 -
ANZ Journal of Surgery Jan 2020Window of opportunity therapies, which involve short-term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in... (Review)
Review
Window of opportunity therapies, which involve short-term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone-receptor positive breast cancer, a 2-week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision-making regarding treatment options. Changes in short-term biomarker endpoints such as cell proliferation measured by Ki-67 can act as surrogate markers of long-term outcomes. Paired tissues obtained pre- and post-investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.
Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Breast Neoplasms; Combined Modality Therapy; Evidence-Based Medicine; Female; Humans; Mastectomy; Neoadjuvant Therapy; Prognosis
PubMed: 31770829
DOI: 10.1111/ans.15487 -
Journal of Internal Medicine Oct 2020
Topics: Biomarkers; Cardiovascular Diseases; Coronary Disease; Humans; Lysine; Methylamines; Myocardial Infarction; Oxides; Virulence Factors
PubMed: 32424985
DOI: 10.1111/joim.13086 -
Cells Oct 2021Schizophrenia is a neuropsychiatric disorder characterized by dissociation of thoughts, idea, identity, and emotions. It has no central pathophysiological mechanism and... (Review)
Review
Schizophrenia is a neuropsychiatric disorder characterized by dissociation of thoughts, idea, identity, and emotions. It has no central pathophysiological mechanism and precise diagnostic markers. Despite its high heritability, there are also environmental factors implicated in the development of schizophrenia. Epigenetic factors are thought to mediate the effects of environmental factors in the development of the disorder. Epigenetic modifications like DNA methylation are a risk factor for schizophrenia. Targeted gene approach studies attempted to find candidate gene methylation, but the results are contradictory. Genome-wide methylation studies are insufficient in literature and the available data do not cover different populations like the African populations. The current genome-wide studies have limitations related to the sample and methods used. Studies are required to control for these limitations. Integration of DNA methylation, gene expression, and their effects are important in the understanding of the development of schizophrenia and search for biomarkers. There are currently no precise and functional biomarkers for the disorder. Several epigenetic markers have been reported to be common in functional and peripheral tissue. This makes the peripheral tissue epigenetic changes a surrogate of functional tissue, suggesting common epigenetic alteration can be used as biomarkers of schizophrenia in peripheral tissue.
Topics: Biomarkers; DNA Methylation; Epigenesis, Genetic; Genome-Wide Association Study; Humans; Precision Medicine; Schizophrenia
PubMed: 34831111
DOI: 10.3390/cells10112890 -
American Journal of Respiratory and... May 2021
Topics: Biomarkers; Humans; Hypertension, Pulmonary; Lung Neoplasms; Prognosis
PubMed: 33789070
DOI: 10.1164/rccm.202103-0740ED -
Statistics in Medicine Nov 2022In comparative effectiveness research (CER), leveraging short-term surrogates to infer treatment effects on long-term outcomes can guide policymakers evaluating new...
In comparative effectiveness research (CER), leveraging short-term surrogates to infer treatment effects on long-term outcomes can guide policymakers evaluating new treatments. Numerous statistical procedures for identifying surrogates have been proposed for randomized clinical trials (RCTs), but no methods currently exist to evaluate the proportion of treatment effect (PTE) explained by surrogates in real-world data (RWD), which have become increasingly common. To address this knowledge gap, we propose inverse probability weighted (IPW) and doubly robust (DR) estimators of an optimal transformation of the surrogate and the corresponding PTE measure. We demonstrate that the proposed estimators are consistent and asymptotically normal, and the DR estimator is consistent when either the propensity score model or outcome regression model is correctly specified. Our proposed estimators are evaluated through extensive simulation studies. In two RWD settings, we show that our method can identify and validate surrogate markers for inflammatory bowel disease (IBD).
Topics: Humans; Models, Statistical; Comparative Effectiveness Research; Computer Simulation; Propensity Score; Biomarkers
PubMed: 36062392
DOI: 10.1002/sim.9569 -
Current Opinion in Obstetrics &... Feb 2020The present article reviews molecular subtyping and genomic characterization of endometrial carcinoma, and the associated therapeutic and prognostic implications. (Review)
Review
PURPOSE OF REVIEW
The present article reviews molecular subtyping and genomic characterization of endometrial carcinoma, and the associated therapeutic and prognostic implications.
RECENT FINDINGS
Endometrial cancer has historically been classified through histology into endometrioid and nonendometrioid subtypes with poor prognostic predictability. Molecular classification through genomic analysis now allows for a major advance in characterization. Four distinct subgroups have been identified: polymerase (POLE) ultramutated, microsatellite unstable, copy number-low--microsatellite stable, and copy number-high-'serous-like'. These subtypes have prognostic implications and may aid in the identification of early-stage patients who are at high risk for recurrence. Through analysis of surrogate markers (POLE, MSI, and p53) and other validated molecular alterations (L1CAM), it is possible to obtain an integrated molecular risk profile that relates to prognosis. Studies utilizing this risk profile in order to identify patients who may benefit from adjuvant treatment for early-stage disease are on-going.
SUMMARY
Molecular characterization of endometrial cancer into subgroups has enhanced prognostic and therapeutic implications, contrary to traditional risk stratification. Further development of an integrated molecular risk profile may identify patients who could most benefit from adjuvant treatment following surgery and tailor treatment decisions in the recurrent setting.
Topics: Biomarkers, Tumor; DNA Copy Number Variations; Endometrial Neoplasms; Female; Genomics; Humans; Microsatellite Instability; Mutation; Neoplasm Recurrence, Local; Risk Assessment
PubMed: 31851045
DOI: 10.1097/GCO.0000000000000602