-
Journal of Parkinson's Disease 2021There is mounting evidence that Parkinson's disease (PD) and Alzheimer's disease (AD) share neuropathological hallmarks, while similar types of biomarkers are being... (Review)
Review
There is mounting evidence that Parkinson's disease (PD) and Alzheimer's disease (AD) share neuropathological hallmarks, while similar types of biomarkers are being applied to both. In this review we aimed to explore similarities and differences between PD and AD at both the neuropathology and the biomarker levels, specifically focusing on protein aggregates and synapse dysfunction. Thus, amyloid-β peptide (Aβ) and tau lesions of the Alzheimer-type are common in PD and α-synuclein Lewy-type aggregates are frequent findings in AD. Modern neuropathological techniques adding to routine immunohistochemistry might take further our knowledge of these diseases beyond protein aggregates and down to their presynaptic and postsynaptic terminals, with potential mechanistic and even future therapeutic implications. Translation of neuropathological discoveries to the clinic remains challenging. Cerebrospinal fluid (CSF) and positron emission tomography (PET) markers of Aβ and tau have been shown to be reliable for AD diagnosis. Conversely, CSF markers of α-synuclein have not been that consistent. In terms of PET markers, there is no PET probe available for α-synuclein yet, while the AD PET markers range from consistent evidence of their specificity (amyloid imaging) to greater uncertainty of their reliability due to off-target binding (tau imaging). CSF synaptic markers are attractive, still needing more evidence, which currently suggests those might be non-specific markers of disease progression. It can be summarized that there is neuropathological evidence that protein aggregates of AD and PD are present both at the soma and the synapse. Thus, a number of CSF and PET biomarkers beyond α-synuclein, tau and Aβ might capture these different faces of protein-related neurodegeneration. It remains to be seen what the longitudinal outcomes and the potential value as surrogate markers of these biomarkers are.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Humans; Parkinson Disease; Protein Aggregates; Synapses; tau Proteins
PubMed: 33325398
DOI: 10.3233/JPD-202323 -
Scientific Reports May 2022Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a...
Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a good correlation coefficient (CC). Since Ki67 is one of the major contributors to Oncotype DX, it is conceivable that Ki67 expression and the recurrence score (RS) obtained by the multigene panel are positively correlated. We decided first to test to what extent conventional and digital Ki67 quantification methods correlate in daily practice and, second, to determine which of these methods correlates better with the prognostic capacity of the Oncotype DX test. Both Ki67 evaluations were performed in 89 core biopsies with a diagnosis of estrogen receptor (ER) positive HER2-negative breast cancer (BC). Cases were, thus, classified twice for surrogate subtype: first by conventional analysis and then by digital evaluation. The Oncotype RS was obtained in 55 cases that were subsequently correlated to Ki67 evaluation by both methods. Conventional and digital Ki67 evaluation showed good concordance and correlation (CC = 0.81 (95% CI 0.73-0.89)). The correlation of Oncotype DX risk groups and surrogate derived subtypes was slightly higher for the digital technique (r = 0.46, p < 0.01) compared to the conventional method (r = 0.39, p < 0.01), even though both were statistically significant. In conclusion, we show that digital evaluation could be an alternative to conventional counting, and also has advantages for predicting the risk established by the Oncotype DX test in ER-positive BC. This study also supports the importance of an accurate Ki67 analysis which can influence the decision to submit ER-positive HER2-negative BC to prognostic molecular platforms.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Ki-67 Antigen; Neoplasm Recurrence, Local; Prognosis; Receptor, ErbB-2; Receptors, Estrogen
PubMed: 35581229
DOI: 10.1038/s41598-022-11411-5 -
Journal of Translational Medicine Jul 2017Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and severe disease with a considerable social and economic impact. So far, the etiology is not... (Review)
Review
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a common and severe disease with a considerable social and economic impact. So far, the etiology is not known, and neither a diagnostic marker nor licensed treatments are available yet. The EUROMENE network of European researchers and clinicians aims to promote cooperation and advance research on ME/CFS. To improve diagnosis and facilitate the analysis of clinical trials surrogate markers are urgently needed. As a first step for developing such biomarkers for clinical use a database of active biomarker research in Europe was established called the ME/CFS EUROMENE Biomarker Landscape project and the results are presented in this review. Further we suggest strategies to improve biomarker development and encourage researchers to take these into consideration for designing and reporting biomarker studies.
Topics: Biomarkers; Europe; Fatigue Syndrome, Chronic; Humans
PubMed: 28747192
DOI: 10.1186/s12967-017-1263-z -
Lipids in Health and Disease Oct 2023Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with...
Fecal short chain fatty acids and urinary 3-indoxyl sulfate do not discriminate between patients with Crohn´s disease and ulcerative colitis and are not of diagnostic utility for predicting disease severity.
BACKGROUND
Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this paper, the fecal SCFAs propionate, acetate, butyrate and isobutyrate of patients with IBD and patients with PSC-IBD and urinary 3-indoxyl sulfate of IBD patients were determined to study associations with disease etiology and severity.
METHODS
SCFA levels in feces of 64 IBD patients and 20 PSC-IBD patients were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Urinary 3-indoxyl sulfate levels of 45 of these IBD patients were analysed by means of reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry. Feces of 17 healthy controls and urine of 13 of these controls were analyzed in parallel. These cohorts had comparable sex distribution and age.
RESULTS
Urinary 3-indoxyl sulfate concentrations (normalized to urinary creatinine levels) was increased (P = 0.030) and fecal isobutyrate levels (normalized to dry weight of the stool sample) of IBD patients were decreased (P = 0.035) in comparison to healthy controls. None of the analyzed metabolites differed between patients with Crohn´s disease (CD) and patients with ulcerative colitis (UC). Fecal acetate and butyrate positively correlated with fecal calprotectin (P = 0.040 and P = 0.005, respectively) and serum C-reactive protein (P = 0.024 and P = 0.025, respectively) in UC but not CD patients. UC patients with fecal calprotectin levels above 150 µg/g, indicating intestinal inflammatory activity, had higher fecal acetate (P = 0.016), butyrate (P = 0.007) and propionate (P = 0.046) in comparison to patients with fecal calprotectin levels < 50 µg/g. Fecal SCFA levels of PSC-IBD and IBD patients were comparable.
CONCLUSIONS
Current findings suggest that analysis of urinary 3-indoxyl-sulfate as well as fecal SCFAs has no diagnostic value for IBD and PSC-IBD diagnosis or monitoring of disease severity.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Indican; Isobutyrates; Propionates; Chromatography, Liquid; Tandem Mass Spectrometry; Inflammatory Bowel Diseases; Fatty Acids, Volatile; Biomarkers; Butyrates; Acetates; Patient Acuity; Feces; Leukocyte L1 Antigen Complex
PubMed: 37789460
DOI: 10.1186/s12944-023-01929-6 -
American Heart Journal Jun 2022The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would...
BACKGROUND
The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would be useful in assessment of HF (eg, severity, adverse outcomes) and risk stratification.
METHODS
A panel of gut-related biomarkers including metabolites of the choline/carnitine- pathway (acetyl-L-carnitine, betaine, choline, γ-butyrobetaine, L-carnitine and trimethylamine-N-oxide [TMAO]) and the gut peptide, Trefoil factor-3 (TFF-3), were investigated in 1,783 patients with worsening HF enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and associations with HF severity and outcomes, and use in risk stratification were assessed.
RESULTS
Metabolites of the carnitine-TMAO pathway (acetyl-L-carnitine, γ-butyrobetaine, L-carnitine, and TMAO) and TFF-3 were associated with the composite outcome of HF hospitalization or all-cause mortality at 3 years (hazards ratio [HR] 2.04-2.93 [95% confidence interval {CI} 1.30-4.71] P≤ .002). Combining the carnitine-TMAO metabolites with TFF-3, as a gut dysfunction panel, showed a graded association; a greater number of elevated markers was associated with higher New York Heart Association class (P< .001), higher plasma concentrations of B-type natriuretic peptide (P< .001), and worse outcome (HR 1.90-4.58 [95% CI 1.19-6.74] P≤ 0.008). Addition of gut dysfunction biomarkers to the contemporary BIOSTAT HF risk model also improved prediction for the aforementioned composite outcome (C-statistics P≤ .011, NRI 13.5-21.1 [95% CI 2.7-31.9] P≤ .014).
CONCLUSIONS
A panel of biomarkers of gut dysfunction showed graded association with severity of HF and adverse outcomes. Biomarkers as surrogate markers are potentially useful for assessment of gut dysfunction to HF pathophysiology and in risk stratification.
Topics: Acetylcarnitine; Biomarkers; Carnitine; Choline; Chronic Disease; Heart Failure; Humans
PubMed: 35278373
DOI: 10.1016/j.ahj.2022.03.002 -
Oxidative Medicine and Cellular... 2015Obstructive sleep apnea (OSA) is a frequent disease mainly affecting obese people and caused by repetitive collapse of the upper airways during sleep. The increased... (Review)
Review
Obstructive sleep apnea (OSA) is a frequent disease mainly affecting obese people and caused by repetitive collapse of the upper airways during sleep. The increased morbidity and mortality of OSA are mainly thought to be the consequence of its adverse effects on cardiovascular (CV) health. In this context, oxidative stress induced by nocturnal intermittent hypoxia has been identified to play a major role. This is suggested by biomarker studies in OSA patients showing excessively generated reactive oxygen species from leukocytes, reduced plasma levels of nitrite and nitrate, increased lipid peroxidation, and reduced antioxidant capacity. Biopsy studies complement these findings by demonstrating reduced endothelial nitric oxide synthase expression and increased nitrotyrosine immunofluorescence in the vasculature of these patients. Furthermore, oxidative stress in OSA correlates with surrogate markers of CV disease such as endothelial function, intima-media thickness, and high blood pressure. Continuous positive airway pressure therapy reverses oxidative stress in OSA. The same may be true for antioxidants; however, more studies are needed to clarify this issue.
Topics: Biomarkers; Cardiovascular Diseases; Carotid Intima-Media Thickness; Humans; Nitric Oxide Synthase Type III; Oxidative Stress; Reactive Oxygen Species; Sleep Apnea, Obstructive
PubMed: 26167241
DOI: 10.1155/2015/608438 -
Canadian Journal of Gastroenterology &... 2020Both nonalcoholic fatty liver disease (NAFLD) and ischemic heart disease have common pathogenic links. Evidence for the association of NAFLD with acute coronary... (Review)
Review
BACKGROUND AND AIMS
Both nonalcoholic fatty liver disease (NAFLD) and ischemic heart disease have common pathogenic links. Evidence for the association of NAFLD with acute coronary syndromes (ACS), complex multivessel coronary artery disease (CAD), and increased mortality risk in ACS patients is still under investigation. Therefore, we conducted a systematic review aiming to clarify these gaps in evidence.
METHODS
We conducted a systematic search on PubMed and EMBASE with predefined keywords searching for observational studies published till August 2020. NAFLD diagnosis was accepted if confirmed through biopsy, imaging techniques, surrogate markers, or codes. Full articles that satisfied our inclusion and exclusion criteria were included in the systematic review. We used the NHLBI quality assessment tool to evaluate included studies.
RESULTS
Seventeen observational studies with a total study population of approximately 21 million subjects were included. Eleven studies evaluated whether NAFLD is an independent risk factor for developing ACS with conflicting results, of which eight studies demonstrated a significant association between NAFLD and ACS, mainly in Asian populations, while three reported a lack of an independent association. Conflicting results were reported in studies conducted in Europe and North America. Moreover, a total of five studies evaluated whether NAFLD and fatty liver severity in ACS patients are associated with a complex multivessel CAD disease, where all studies confirmed a significant association. Furthermore, seven out of eight studies evaluating NAFLD and hepatic steatosis severity as a predictor of all-cause and cardiovascular mortality and in-hospital major adverse cardiovascular events (MACE) in ACS patients demonstrated a significant independent association.
CONCLUSIONS
NAFLD patients are associated with an independently increased risk of developing ACS, mainly in Asian populations, with inconsistent results in North American and European individuals. Moreover, NAFLD and hepatic steatosis severity were both independently correlated with complex multivessel CAD, mortality, and in-hospital MACE in ACS patients.
Topics: Acute Coronary Syndrome; Biomarkers; Coronary Artery Disease; Humans; Non-alcoholic Fatty Liver Disease; Risk Factors
PubMed: 33313020
DOI: 10.1155/2020/8825615 -
Chinese Clinical Oncology Oct 2019Surgeons are exploring the use of molecular biomarkers in patients with colorectal liver metastases (CLM) to improve preoperative prognostication and selection. This is... (Review)
Review
Surgeons are exploring the use of molecular biomarkers in patients with colorectal liver metastases (CLM) to improve preoperative prognostication and selection. This is important because surrogate markers of tumor biology remain insufficient to predict clinical outcomes. In the current literature, there is agreement for the association between RAS and BRAF mutations and poor long-term outcome after hepatectomy. While this knowledge is gradually being implemented in the clinical work-up of patients, their limitations and implications have yet to be fully understood. Recent data indicate that combinations of coexisting mutations may refine the molecular scoring into footprints of good and bad. This already complex information must be interpreted in light of recent understanding of clonal heterogeneity and genetic diversity of colorectal cancer and CLM. In the clinical settings, it is important to approach new insight into molecular biomarkers with caution. However, it is likely that in the future, genomic analysis will determine which patient is amenable to surgery or not, the timing of surgery versus other modalities, as well as how to approach the metastases technically. Here we review current knowledge about molecular biomarkers in the treatment of CLM and the limitations to consider at the translation to clinical practice.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Humans; Liver Neoplasms; Mutation; Preoperative Period; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 31500431
DOI: 10.21037/cco.2019.08.02 -
Clinical Autonomic Research : Official... Dec 2023There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light...
PURPOSE
There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to cerebrospinal fluid (NfL-c) as a diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression.
METHODS
Well-characterized patients with early MSA (n = 32), Parkinson's disease (PD; n = 21), and matched controls (CON; n = 15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high-sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression.
RESULTS
Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson, r = 0.99), while correlation between NfL-c and -p was only moderate (r = 0.66). NfL was significantly higher in MSA compared with CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL nor baseline NfL were significantly associated with changes in clinical markers of disease severity.
CONCLUSIONS
These findings confirm NfL-c as a faithful diagnostic marker of MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time and was not predictive of clinical disease progression.
Topics: Multiple System Atrophy; Neurofilament Proteins; Biomarkers; Longitudinal Studies; Humans; Immunoassay; Reproducibility of Results; Parkinson Disease; Male; Female; Middle Aged; Aged
PubMed: 37603107
DOI: 10.1007/s10286-023-00974-6 -
International Journal of Molecular... Aug 2022Primary biliary cholangitis (PBC) has a wide variation in clinical presentation and course. There is no significant correlation between these symptoms and the disease...
Primary biliary cholangitis (PBC) has a wide variation in clinical presentation and course. There is no significant correlation between these symptoms and the disease stage, although patients with more advanced stages generally have more symptoms. It is important to develop biomarkers in order to identify patients with an increased risk of complications and end-stage liver disease. This study investigated surrogate markers for risk estimation of PBC-related complications, including a study population of 77 patients with PBC who underwent liver biopsy and were measured for serum levels of macrophage activation markers, soluble CD163 (sCD163), soluble mannose receptor (sMR), and zonulin. Patients with PBC were divided into symptomatic (Group S, n = 20) and asymptomatic (Group A, n = 57) groups. The correlations of histological stages based on both Scheuer and Nakanuma classifications with the three serum markers were investigated. The Nakanuma classification involves grading for liver fibrosis and bile duct loss. The three biomarkers were assessed for their diagnostic ability to identify patients with PBC having high risk of developing complications. The predictive factors of these complications were examined as well. Group S had significantly higher serum sMR (p = 0.011) and sCD163 (p = 0.048) levels versus Group A. A composite index of sMR and sCD163 measurements had significantly better prediction performance than sCD163 alone (p = 0.012), although not when compared to sMR alone (p = 0.129). Serum sMR was an independent factor for developing complications on both univariate (Odds ratio (OR) = 30.20, 95% confidence interval (95% CI): 3.410−267.0, p = 0.00220), and multivariate (OR = 33.70, 95% CI: 3.6600−311.0, p = 0.0019) analyses. Patients with PBC having sMR of ≥56.6 had a higher incidence of clinical complications versus those with a sMR of <56.6. Serum sMR predicts the development of complications in patients with PBC. sMR plus sCD163 showed better predictive power than either marker alone, although the addition of sCD163 did not improve the predictive power of sMR. Future prospective studies are required in order to validate the findings of the present study.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Humans; Lectins, C-Type; Liver Cirrhosis, Biliary; Macrophage Activation; Mannose Receptor; Mannose-Binding Lectins; Receptors, Cell Surface
PubMed: 36077228
DOI: 10.3390/ijms23179814