Use Of Biomarkers Research Articles

A comprehensive non-targeted approach for the analysis of biomarkers in exhaled breath across different nicotine product categories

In the context of the evolving landscape of nicotine consumption, the assessment of biomarkers plays a crucial role in understanding the health impact of different product categories. Exhaled breath (EB) emerges as a promising, non-invasive matrix for biomarker analysis, complementary to conventional urine and plasma data. This study explores distinctive EB biomarker profiles among users of combustible cigarettes (CC), heated tobacco products (HTP), electronic cigarettes (EC), smokeless/oral tobacco (OT), and oral/dermal nicotine products (NRT). We have successfully developed and validated a non-targeted GC-TOF-MS method for the analysis of EB samples across the aforementioned product categories. A total of 66 compounds were identified, with significantly elevated levels in at least one study group. The study found that CC users had higher levels of established VOCs associated with smoking, which supports the proof-of-concept of the method. Breathomic analysis identified increased levels of p-cymene and α-pinene in EC users, while HTP users showed potential biomarker candidates like γ-butyrolactone. This study underscores the utility of EB biomarkers for a comprehensive evaluation of diverse nicotine products. The unique advantages offered by EB analysis position it as a valuable tool for understanding the relationship between exposure and health outcomes.

Enhanced Association of Novel Cardiovascular Biomarkers Fetuin-A and Catestatin with Serological and Inflammatory Markers in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with increased cardiovascular disease (CVD) risk and mortality. This work aimed to evaluate the serum levels of the novel CV biomarkers fetuin-A (fet-A), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), interleukin-32 (IL-32), and catestatin (CST) in RA patients and their associations with RA parameters and CVD markers. A cohort of 199 RA patients was assessed for traditional CVD risk factors, RA disease activity, and biomarker levels. Carotid ultrasound was used to measure carotid intima-media thickness (cIMT) and carotid plaque presence (cPP). Multivariate analyses examined correlations between biomarkers and RA parameters, serological markers, and CVD markers. Adjusted models showed that elevated CST expression levels were associated with rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity (OR = 2.45, p = 0.0001 and OR = 1.48, p = 0.04, respectively) in the overall cohort and for RF in men and women, respectively. In addition, fet-A concentration was inversely associated with the erythrocyte sedimentation rate (ESR) in the overall cohort (β = -0.15, p = 0.038) and in women (β = -0.25, p = 0.004). Fet-A levels were also negatively correlated with disease activity (DAS28-ESR) scores (β = -0.29, p = 0.01) and fibrinogen concentration (β = -0.22, p = 0.01) in women. No adjusted associations were observed for Gal-3, DKK-1 or IL32 concentration. The study revealed no significant associations between the biomarkers and cIMT or cPP. The measurement of CST and fet-A levels could enhance RA patient management and prognosis. However, the utility of biomarkers for evaluating CV risk via traditional surrogate markers is limited, highlighting the need for continued investigations into their roles in RA.

Genetic spectrum features and diagnostic accuracy of four plasma biomarkers in 248 Chinese patients with frontotemporal dementia.

Frontotemporal dementia (FTD) is characterized by phenotypic and genetic heterogeneities. However, reports on the large Chinese FTD cohort are lacking. Two hundred forty-eight patients with FTD were enrolled. All patients and 2010 healthy controls underwent next generation sequencing. Plasma samples were analyzed for glial fibrillary acidic protein (GFAP), α-synuclein (α-syn), neurofilament light chain (NfL), and phosphorylated tau protein 181 (p-tau181). Gene sequencing identified 48 pathogenic or likely pathogenic mutations in a total of 19.4% of patients with FTD (48/248). The most common mutation was the C9orf72 dynamic mutation (5.2%, 13/248). Significantly increased levels of GFAP, α-syn, NfL, and p-tau181 were detected in patients compared to controls (all p<0.05). GFAP and α-syn presented better performance for diagnosing FTD. We investigated the characteristics of phenotypic and genetic spectrum in a large Chinese FTD cohort, and highlighted the utility of plasma biomarkers for diagnosing FTD. This study used a frontotemporal dementia (FTD) cohort with a large sample size in Asia to update and reveal the clinical and genetic spectrum, and explore the relationship between multiple plasma biomarkers and FTD phenotypes as well as genotypes. We found for the first time that the C9orf72 dynamic mutation frequency ranks first among all mutations, which broke the previous impression that it was rare in Asian patients. Notably, it was the first time the C9orf72 G4C2 repeat expansion had been identified via whole-genome sequencing data, and this was verified using triplet repeat primed polymerase chain reaction (TP-PCR). We analyzed the diagnostic accuracy of four plasma biomarkers (glial fibrillary acidic protein [GFAP], α-synuclein [α-syn], neurofilament light chain [NfL], and phosphorylated tau protein 181 [p-tau181]) at the same time, especially for α-syn being included in the FTD cohort for the first time, and found GFAP and α-syn had the highest diagnostic accuracy for FTD and its varied subtypes.

Urine metabolomic profiles of autism and autistic traits-A twin study.

Currently, there are no reliable biomarkers for autism diagnosis. The heterogeneity of autism and several co-occurring conditions are key challenges to establishing these. Here, we used untargeted mass spectrometry-based urine metabolomics to investigate metabolic differences for autism diagnosis and autistic traits in a well-characterized twin cohort (N = 105). We identified 208 metabolites in the urine samples of the twins. No clear, significant metabolic drivers for autism diagnosis were detected when controlling for other neurodevelopmental conditions. However, we identified nominally significant changes for several metabolites. For instance, phenylpyruvate (p = 0.019) and taurine (p = 0.032) were elevated in the autism group, while carnitine (p = 0.047) was reduced. We furthermore accounted for the shared factors, such as genetics within the twin pairs, and report additional metabolite differences. Based on the nominally significant metabolites for autism diagnosis, the arginine and proline metabolism pathway (p = 0.024) was enriched. We also investigated the association between quantitative autistic traits, as measured by the Social Responsiveness Scale 2nd Edition, and metabolite differences, identifying a greater number of nominally significant metabolites and pathways. A significant positive association between indole-3-acetate and autistic traits was observed within the twin pairs (adjusted p = 0.031). The utility of urine biomarkers in autism, therefore, remains unclear, with mixed findings from different study populations.

Misdiagnoses of psychiatric disorders and the utility of diagnostic microRNA biomarkers

Misdiagnoses of psychiatric disorders and the utility of diagnostic microRNA biomarkers

Systems Approach to Investigate the Role of Fruit and Vegetable Types on Vascular Function in Pre-Hypertensive Participants: Protocol and Baseline Characteristics of a Randomised Crossover Dietary Intervention.

The evidence on the impact of fruits and vegetable types on cardiovascular risk factors remains limited. Specifically, the utilisation of biomarkers to objectively measure dietary compliance and metabolic responses is emerging. This protocol and baseline characteristics of a pilot randomised controlled, crossover, dietary intervention study aimed to examine the effects of citrus fruits, cruciferous vegetables, or common fruits and vegetables on cardiovascular risk factors. A total of 39 volunteers with untreated prehypertension was recruited and consumed a standardised, provided diet with eight daily portions of citrus fruits and cruciferous vegetables, common fruits and vegetables, or a low fruit and vegetable diet (two portions/d, control diet) in a random order for 2 weeks each, separated by a wash-out week. A targeted cohort-based recruitment strategy was utilised and resulted in 74% of participants recruited by re-contacting preselected individuals from two cohort studies with a 15% average enrolment rate. Participants had an average age of 54.4 years (±6.1 years), BMI of 27.9 kg/m2, and BP of 135/81 mmHg and were mainly male (67%). The primary outcome was office blood pressure; secondary outcomes included arterial stiffness, lipid profiles, inflammation, cognitive function, and subjective mood. Biofluids, i.e., 24 h urine, stool, and blood samples, were collected for biomarker measurements with multiple metabolomic platforms and the gut microbial composition, together with traditional dietary biomarkers.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

The clinical relevance of the new criteria for cirrhotic cardiomyopathy and future directions.

Cardiac dysfunction in patients with liver disease has been recognized since the 1950s. Initially attributed to shared risk factors, it is now evident that cardiac dysfunction in patients with cirrhosis can occur in the absence of known cardiac, i.e., coronary artery and valvular heart disease, and across all etiologies for cirrhosis. In 1996 this myocardial dysfunction was termed cirrhotic cardiomyopathy (CCM). The pathophysiologic mechanisms underlying CCM include impaired beta-adrenergic membrane function and circulating proinflammatory and cardiotoxic substances. In 2005, the first diagnostic criteria for CCM were introduced enabling greater sensitivity and accuracy of diagnosis. Since 2005, advancements in echocardiographic methods and better understanding of the pathophysiology of cardiac dysfunction in patients with cirrhosis necessitated revision of CCM criteria. Changes in CCM criteria included removal of blunted contractile or heart rate response on stress testing and addition of global longitudinal systolic strain. Refinement of criteria for diastolic dysfunction were also incorporated into the new diagnostic approach. Since 2020, the prevalence of the disorder and clinical considerations for pre-transplant, peritransplant, and post-transplant patients with cirrhosis have been further evaluated and CCM was found to adversely impact clinical outcomes during all three phases of care. Future research considerations should address the timing of universal echocardiographic screening for patients with cirrhosis, utility of biomarkers in aiding CCM diagnosis, impact of CCM on right heart function, and role of anti-remodeling agents post-liver transplant (post-LT).

Neurodegenerative biomarkers in different chambers of the eye relative to plasma: an agreement validation study

BackgroundProtein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer’s disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood.MethodsIn this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland–Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma.ResultsSeventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland–Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p < 0.001) and NfL (r = 0.7; p < 0.001).ConclusionAD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease.

Untargeted Blood Lipidomics Analysis in Critically Ill Pediatric Patients with Ventilator-Associated Pneumonia: A Pilot Study.

This study aims to explore the diagnostic potential of blood lipid profiles in suspected ventilator-associated pneumonia (VAP). Early detection of VAP remains challenging for clinicians due to subjective clinical criteria and the limited effectiveness of current diagnostic tests. Blood samples from 20 patients, with ages between 6 months and 15 years, were collected at days 1, 3, 6, and 12, and an untargeted lipidomics analysis was performed using a Ultra high Pressure Liquid Chromatography hyphenated with High Resolution Mass Spectrometry UPLC-HRMS (TIMS-TOF/MS) platform. Patients were stratified based on modified pediatric clinical pulmonary index score (mCPIS) into high (mCPIS ≥ 6, n = 12) and low (mCPIS < 6, n = 8) VAP suspicion groups. With the untargeted lipid profiling, we were able to identify 144 lipid species from different lipid groups such as glycerophospholipids, glycerolipids, and sphingolipids, in the blood of children with VAP. Multivariate and univariate statistical analyses revealed a distinct distribution of blood lipid profiles between the studied groups, indicating the potential utility of lipid biomarkers in discriminating VAP presence. Additionally, specific lipids were associated with pharyngeal culture results, notably the presence of Klebsiella pneumoniae and Staphylococcus aureus, underscoring the importance of lipid profiling in identifying the microbial etiology of VAP.

Usefulness of Tissue Biomarkers versus Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prostate Cancer Biochemical Recurrence after Radical Prostatectomy.

Despite curative-intent local therapy, approximately 27% to 53% of prostate cancer (PCa) patients experience prostate-specific antigen (PSA) recurrence, known as biochemical recurrence (BCR). BCR significantly raises the risk of PCa-related morbidity and mortality, yet there is no consensus on optimal management. Prostate-specific membrane antigen-positron emission tomography (PSMA PET) has emerged as highly sensitive imaging, distinguishing local recurrences from distant metastases, crucially influencing treatment decisions. Genomic biomarkers such as Decipher, Prolaris, and Oncotype DX contribute to refining recurrence risk profiles, guiding decisions on intensifying adjuvant therapies, like radiotherapy and androgen deprivation therapy (ADT). This review assesses PSMA PET and biomarker utility in post-radical prostatectomy BCR scenarios, highlighting their impact on clinical decision-making. Despite their promising roles, the routine integration of biomarkers is limited by availability and cost, requiring further evidence. PSMA PET remains indispensable for restaging and treatment evaluation in these patients. Integrating biomarkers and PSMA PET promises to optimize personalized management strategies for BCR, though more comprehensive consensus-building studies are needed to define their standardized utility in clinical practice.

Exploring Ventilator-Associated Pneumonia: Microbial Clues and Biomarker Insights from a Retrospective Study.

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.

Biomarkers in cardiorenal syndrome, a potential use in precision medicine.

Cardiorenal syndrome refers to the interrelated dysfunction of the heart or kidney resulting in a cascade of feedback mechanisms, hemodynamic, neurohormonal, and immunological and/or biochemical feedback pathways causing damage in the other organ. Cardiorenal syndrome is categorized into five clinical subtypes depending on the perceived primary precipitant of organ injury and is associated with high morbidity and mortality. Therefore, the development of tools for the earliest identification of cardiorenal syndrome in hospitalized patients is of extremely high significance to ameliorate the prognosis and outcome of these patients. There is increasing interest in identifying molecules serving as biomarkers, reflecting hemodynamic changes, heart and kidney damage and/or dysfunction and oxidative stress-induced cell damage or changes in the extracellular matrix of both the heart and kidneys. Biomarkers provide important insights into the pathophysiology of cardiorenal syndrome and are invaluable tools to predict the decrease in renal function during cardiac dysfunction and vice versa. Based on the pathophysiological mechanisms of cardiorenal syndrome, we reviewed and evaluated the available literature on serum and urinary biomarkers as predictors of kidney and/or heart injury. In addition, heart- and kidney-specific biomarkers were also evaluated based ontheir reference to kidney and cardiac (dys)function respectively, and whether they would provide any prediction and prognostication of cardiorenal syndrome. In this article, we discuss the current knowledge on the pathophysiology of different types ofcardiorenal syndrome, examine the clinical utility of candidate biomarkers in the early diagnosis of cardiorenalsyndrome, and guide treatment by evaluating the respective roles of the involved pathophysiological pathways.

Optical coherence tomography angiography in neovascular age-related macular degeneration: comprehensive review of advancements and future perspective.

Optical coherence tomography angiography (OCTA) holds promise in enhancing the care of various retinal vascular diseases, including neovascular age-related macular degeneration (nAMD). Given nAMD's vascular nature and the distinct vasculature of macular neovascularization (MNV), detailed analysis is expected to gain significance. Research in artificial intelligence (AI) indicates that en-face OCTA views may offer superior predictive capabilities than spectral domain optical coherence tomography (SD-OCT) images, highlighting the necessity to identify key vascular parameters. Analyzing vasculature could facilitate distinguishing MNV subtypes and refining diagnosis. Future studies correlating OCTA parameters with clinical data might prompt a revised classification system. However, the combined utilization of qualitative and quantitative OCTA biomarkers to enhance the accuracy of diagnosing disease activity remains underdeveloped. Discrepancies persist regarding the optimal biomarker for indicating an active lesion, warranting comprehensive prospective studies for validation. AI holds potential in extracting valuable insights from the vast datasets within OCTA, enabling researchers and clinicians to fully exploit its OCTA imaging capabilities. Nevertheless, challenges pertaining to data quantity and quality pose significant obstacles to AI advancement in this field. As OCTA gains traction in clinical practice and data volume increases, AI-driven analysis is expected to further augment diagnostic capabilities.

Reader Response: Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury.

Reader Response: Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury.

Age-Dependent Differences in Blood Levels of Glial Fibrillary Acidic Protein but Not Ubiquitin Carboxy-Terminal Hydrolase L1 in Children.

Despite the growing evidence of the clinical utility of blood-brain biomarkers in adults with traumatic brain injury (TBI), less is known about the performance of these biomarkers in children. We characterize age-dependent differences in levels of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in children without TBI. Plasma biobank specimens from children and adolescents aged 0-<19 years without TBI were obtained, and UCH-L1 and GFAP levels were quantified. The relationship between age and biomarker expression was determined using previously defined aged epochs (<3.5 years, 3.5 years to <11 years, 11 years and older), then biomarker levels were compared with established thresholds for ruling out the need for a head CT in adults with a mild TBI (mTBI) (UCH-L1 400 pg/mL, GFAP 35 pg/mL). The age range of the 366 control patients was 3 months-18 years. There was a significant negative association between age and GFAP but not UCH-L1. Only 1.4% of samples exceeded the UCH-L1 cutoff; however, 20% of samples exceeded the GFAP cutoff and 100% children younger than 3.5 years had values that exceeded the cutoff. Age seems to modify physiologic plasma GFAP levels. Diagnostic cutoffs for TBI based on GFAP but not UCH-L1 and may need to be adjusted in children younger than 11 years.

Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies.

Triple-negative breast cancer (TNBC) is a heterogeneous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted toward tumors carrying a specific genomic, transcriptomic, or protein biomarker, it is poorly understood how these biomarkers are correlated. To better understand the molecular features of TNBC and their correlation with one another, we performed multimodal profiling on a cohort of 95 TNBC. Our approach involved quantifying tumor-infiltrating lymphocytes through hematoxylin and eosin staining, assessing the abundance of retinoblastoma, androgen receptor, and PDL1 proteins through IHC, and carrying out transcriptomic profiling using the NanoString BC360 platform, targeted DNA sequencing on a subset of cases, as well as evaluating associations with overall survival. Levels of RB1 mRNA and RB proteins are better correlated with markers of retinoblastoma functionality than RB1 mutational status. Luminal androgen receptor tumors clustered into two groups with transcriptomes that cluster with either basal or mesenchymal tumors. Tumors classified as PDL1-positive by the presence of immune or tumor cells showed similar biological characteristics. HER2-low TNBC showed no distinct biological phenotype when compared with HER2-zero. The majority of TNBC were classified as basal or HER2-enriched by PAM50, the latter showing significantly improved overall survival. Our study contributes new insights into biomarker utility for identifying suitable TNBC therapies and the intercorrelations between genomic, transcriptomic, protein, and cellular biomarkers. Additionally, our rich data resource can be used by other researchers to explore the interplay between DNA, RNA, and protein biomarkers in TNBC.

Unlocking the Potential of Vessel Density and the Foveal Avascular Zone in Optical Coherence Tomography Angiography as Biomarkers in Alzheimer's Disease.

Alzheimer's disease is the most prevalent form of dementia. Apart from its traditional clinical diagnostic methods, novel ocular imaging biomarkers have the potential to significantly enhance the diagnosis of Alzheimer's disease. Ophthalmologists might be able to play a crucial role in this multidisciplinary approach, aiding in the early detection and diagnosis of Alzheimer's disease through the use of advanced retinal imaging techniques. This systematic literature review the utilization of optical coherence tomography angiography biomarkers, specifically vessel density and the foveal avascular zone, for the diagnosis of Alzheimer's disease. A comprehensive search was performed across multiple academic journal databases, including 11 relevant studies. The selected studies underwent thorough analysis to assess the potential of these optical coherence tomography angiography biomarkers as diagnostic tools for Alzheimer's disease. The assessment of vessel density and the foveal avascular zone have emerged as a promising avenue for identifying and diagnosing Alzheimer's disease. However, it is imperative to acknowledge that further targeted investigations are warranted to address the inherent limitations of the existing body of literature. These limitations encompass various factors such as modest sample sizes, heterogeneity among study populations, disparities in optical coherence tomography angiography imaging protocols, and inconsistencies in the reported findings. In order to establish the clinical utility and robustness of these biomarkers in Alzheimer's disease diagnosis, future research endeavors should strive to overcome these limitations by implementing larger-scale studies characterized by standardized protocols and comprehensive assessments.

Clinical Utility of Machine Learning-Derived Vocal Biomarkers in the Management of Heart Failure.

This study aimed to systematically evaluate voice symptoms during heart failure (HF) treatments and to exploratorily extract HF-related vocal biomarkers. This single-center, prospective study longitudinally acquired 839 audio files from 59 patients with acute decompensated HF. Patients' voices were analyzed along with conventional HF indicators (New York Heart Association [NYHA] class, presence of pulmonary congestion and pleural effusion on chest X-ray, and B-type natriuretic peptide [BNP]) and GOKAN scores based on the assessment of a cardiologist. Machine-learning (ML) models to estimate HF conditions were created using a Light Gradient Boosting Machine. Voice analysis identified 27 acoustic features that correlated with conventional HF indicators and GOKAN scores. When creating ML models based on the acoustic features, there was a significant correlation between actual and ML-derived BNP levels (r=0.49; P<0.001). ML models also identified good diagnostic accuracies in determining HF conditions characterized by NYHA class ≥2, BNP ≥300 pg/mL, presence of pulmonary congestion or pleural effusion on chest X-ray, and decompensated HF (defined as NYHA class ≥2 and BNP levels ≥300 pg/mL; accuracy: 75.1%, 69.1%, 68.7%, 66.4%, and 80.4%, respectively). The present study successfully extracted HF-related acoustic features that correlated with conventional HF indicators. Although the data are preliminary, ML models based on acoustic features (vocal biomarkers) have the potential to infer various HF conditions, which warrant future studies.

Diagnostic utility of sortilin & other biomarkers in the diagnosis of carotid & coronary atherosclerosis in individuals with arterial hypertension.

Background & objectives Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. The aim of this investigation was to study the role of biological markers in predicting the risk of carotid and coronary artery atherosclerosis. Methods A total of 161 males in the age group of 30-65 yr were included in this study. All participants underwent biochemical analyses [cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, glucose, (interleukin) IL-8, IL-10, (proprotein convertase inhibitors subtilisin/kexin type 9) PCSK9, sortilin, creatinine]; ECG; echocardiography; coronary angiography; ultrasound doppler of brachiocephalic arteries. Based on PCSK9 levels, participants were divided into four groups: group 1, n=41 individuals with PCSK9 level of 100-250 ng/ml; group 2, n=37 individuals with PCSK9 level of 251-400 ng/ml; group 3, n=51 individuals with PCSK9 level of 401-600 ng/ml and group 4, n=32 individuals with PCSK9 level of 601-900 ng/ml. Results Sortilin level was the highest in group 2. Group 3 individuals had the highest level of IL-8. Correlation analysis of the entire data set revealed the relationship of relative left ventricular thickness index with age, cardiovascular risk, body mass index, intima-media thickness and left ventricular mass index; sortilin had a negative relationship of weak strength with age and smoking, a direct relationship between the risk of cardiovascular complications and with IL-10. Interpretation & conclusions Sortilin is the innovative marker of CVDs. In the present investigation, we demonstrated the clear increase in the inflammatory markers (IL-8) in individuals with subclinical atherosclerosis. This fact can be explained by the oxygen stress activation. In individuals with coronary artery stenosis (50% and more), the increase in IL-10 levels demonstrates, to our opinion, the activation of antioxidant protection activation.