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Diagnostics
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Clinical Prognostic and Predictive Biomarkers, 4th Edition
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Clinical Prognostic and Predictive Biomarkers, 4th Edition

A Special Issue of Diagnostics (ISSN 2075-4418) belonging to the section "Clinical Diagnosis and Prognosis".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 2928

Editors

Prof. Dr. Yuli Huang

E-Mail Website
Guest Editor
Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan 528300, China
Interests: cardiovascular disease; heart failure; diabetes; biomarkers; public health; prevention
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Peisong Chen

E-Mail Website
Guest Editor
Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
Interests: laboratory medicine; precision medicine; risk prediction; clinical biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biomarkers are measures of biological variables that can be detected in organ tissues, blood, or other body fluids. They can be divided mainly into two main types: prognostic and predictive biomarkers. Prognostic biomarkers are associated with the clinical outcomes (e.g., disease progression, recurrence, and death) of the disease of interest and are used to identify those with more aggressive disease status. Predictive biomarkers are used to identify individuals with a higher likelihood of response to a particular treatment, which allows for better identification of those who are more likely to benefit from a given treatment. Generally, biomarkers can be either prognostic or predictive, while in some cases they could be used for both prognostic and predictive purposes.

With the significant advances made in proteomics, metabolomics, functional genomics, and bioinformatics, more and more novel biomarkers are being discovered. They play an important role in identifying high-risk individuals, diagnosing disease conditions, and predicting response to therapy and prognosis in multiple fields of clinical medicine, including cardiovascular disease, diabetes, and cancer. Furthermore, they allow us to better understand the mechanisms and molecular pathways of disease development and progression. This deeper knowledge of biomarkers offers the opportunity to develop novel precision and personalized therapies.

In this Special Issue, we aim to provide a platform for communication on the progress of biomarker identification and utilization in healthcare. Topics of interest include, but are not limited to, biomarkers in cardiovascular disease, diabetes, acute and chronic venous disease, and cancer.

Prof. Dr. Yuli Huang
Prof. Dr. Peisong Chen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomarkers
  • prognostic
  • predictive
  • risk stratification
  • cardiovascular disease
  • diabetes
  • cancer
  • hypertension
  • heart failure

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Published Papers (4 papers)

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Research

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19 pages, 3894 KB  
Article
Longitudinal Stress Hyperglycemia Trajectories and Severe Outcome in Patients Hospitalized for Viral Respiratory Infections: A 72-Hour Phenotyping Study
by Ana Maria Mihai, Ovidiu Rosca, Florina Lucaciu, Alexandra Herlo, Talida Georgiana Cut, Matilda Radulescu, Delia Mira Berceanu-Vaduva, Ioana-Melinda Luput-Andrica, Radu Gheorghe Dan, Andra-Elena Saizu, Andreea-Cristina Floruncut, Adelina-Raluca Marinescu and Alexandra Sima
Diagnostics 2026, 16(15), 2310; https://doi.org/10.3390/diagnostics16152310 - 23 Jul 2026
Viewed by 1470
Abstract
Background/Objectives: Patients with diabetes face increased risks during viral respiratory infections. While chronic glycemic control (HbA1c) is a known risk factor, it may fail to capture acute metabolic failure. This study aimed to evaluate the stress hyperglycemia ratio (SHR) at two time points [...] Read more.
Background/Objectives: Patients with diabetes face increased risks during viral respiratory infections. While chronic glycemic control (HbA1c) is a known risk factor, it may fail to capture acute metabolic failure. This study aimed to evaluate the stress hyperglycemia ratio (SHR) at two time points (admission and 72 h) as a prognostic marker. Methods: We conducted a longitudinal analysis of 430 patients (211 with diabetes and 219 without diabetes) hospitalized with viral respiratory infections. The SHR was calculated at admission (SHR_z1) and at 72 h (SHR_z3). The primary outcome was severe clinical deterioration (defined as oxygen requirement >2–HFNO/OTI or mortality). Multivariate logistic regression and ROC curve analysis were used to determine independent predictors and clinical cut-off points. Results: In the global multivariable model (N = 430), continuous SHR_z3 emerged as an independent predictor of severe outcome (OR = 1.86, 95% CI 1.09–3.20, p = 0.0240) alongside chronic glycemic control (HbA1c: OR = 1.41, p < 0.0001) and age (OR = 1.05, p = 0.0001). After stratification, the independent SHR_z3 effect attenuated below statistical significance in both the non-diabetic (p = 0.6168) and diabetic (p = 0.1954) sub-cohorts, while HbA1c (p = 0.0404) and age (p = 0.0036) remained independent predictors within the diabetic subgroup. An exploratory longitudinal phenotype model classifying patients into Stable Normal, Resolvers, Persistent, and Late Spikers showed the highest in-sample discrimination of all models tested (AUC = 0.797, 95% CI 0.756–0.834). Within this model, the Persistent phenotype (SHR ≥ 1.1 sustained at admission and at 72 h) showed a non-significant trend toward higher adjusted odds of severe outcome compared with Stable Normal patients (OR = 1.81, 95% CI 0.91–3.60, p = 0.088) and was associated with a significantly longer hospital stay (Kruskal–Wallis p = 0.004 across phenotypes). Conclusions: Persistent stress hyperglycemia at 72 h is an independent predictor of severe outcome in the unstratified cohort after adjustment for chronic glycemic control, age, and other covariates. Within metabolic strata, the SHR_z3 signal attenuates, and long-standing suboptimal glycemic control (HbA1c) and age dominate, particularly among diabetic patients. Longitudinal SHR trajectories may therefore provide complementary, hypothesis-generating prognostic information when combined with chronic baseline markers, although these findings require external validation in independent cohorts before clinical use. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 4th Edition)
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12 pages, 1180 KB  
Article
Personalized Protocol for the Dynamic Assessment of Functional Biomarkers of Vascular Stiffness: A Novel Diagnostic Tool in P4 Medicine
by Victor N. Dorogovtsev, Dmitry S. Yankevich, Valentina M. Tsareva, Denis A. Punin, Ilya V. Borisov, Julia A. Podolskaya and Andrey V. Grechko
Diagnostics 2026, 16(13), 2001; https://doi.org/10.3390/diagnostics16132001 - 26 Jun 2026
Viewed by 397
Abstract
Background/Objectives: Functional biomarkers of vascular stiffness (FBM-VS) may serve as an effective tool for predicting and monitoring the effectiveness of preventive strategies against accelerated vascular ageing in healthy populations within the framework of P4 medicine. The aim of this study was to perform [...] Read more.
Background/Objectives: Functional biomarkers of vascular stiffness (FBM-VS) may serve as an effective tool for predicting and monitoring the effectiveness of preventive strategies against accelerated vascular ageing in healthy populations within the framework of P4 medicine. The aim of this study was to perform a comparative analysis of a standardized to hydrostatic column height passive head-up tilt test (stHUTT) and a simplified supine-to-sitting test (SST) for measuring FBM-VS in a paired sample of young healthy subjects. Materials and Methods: This observational cross-sectional study included 95 healthy adults aged 18–20 years (54 women and 41 men). Brachial–ankle pulse wave velocity (baPWV) was measured in three positions: baseline supine position (baPWVb), during stHUTT (baPWVst), and after transitioning to a sitting position (baPWVsit). The functional reserve of orthostatic circulatory regulation (FR) and the functional reserve coefficient (FRC) were calculated for the stHUTT (FRst and FRCst) and during the supine-to-sitting test (FRsit and FRCsit). Results: The results showed unidirectional orthostatic changes in baPWV during both tests (significant increase compared to baseline supine values): baPWVst and baPWVsit in stHUTT and during the SST increased from 8.6 [8.1; 9.1] m/s to 13.4 [12.1; 14.4] m/s and to 15.2 [13.4; 16.1] m/s (p < 0.001), respectively. FBM-VS values in the SST were higher compared to stHUTT: FRsit = 6.4 [5.25; 7.75] m/s vs. FRst = 4.85 [3.7; 5.75] m/s (p < 0.001), and FRCsit = 0.74 [0.59;0.9] vs. FRCst = 0.55 [0.45; 0.68] (p < 0.001). The variance of these parameters was also significantly higher in the SST. Spearman rank correlation analysis demonstrated significant positive correlations between biomarkers measured during both orthostatic tests. Conclusions: The supine-to-sitting test may be used for the personalized quantitative assessment of FBM-VS in healthy populations. To assess their prognostic value and to provide personalized long-term monitoring to control the effectiveness of preventive measures against vascular ageing in healthy individuals, a prospective cohort study is required. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 4th Edition)
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17 pages, 1410 KB  
Article
Preoperative OCT Biomarkers as Predictors of Postoperative Functional Outcome Assessed by Microperimetry After Inverted ILM Flap Surgery
by Ovidiu Samoilă, Anca Mădălina Sere, Lăcrămioara Samoilă and Daniel-Corneliu Leucuța
Diagnostics 2026, 16(12), 1919; https://doi.org/10.3390/diagnostics16121919 - 20 Jun 2026
Viewed by 394
Abstract
Background/Objectives: A macular hole represents a significant surgical condition in an increasingly aging population. Advances in surgical techniques, particularly pars plana vitrectomy with inverted internal limiting membrane (ILM) flap, have established high anatomical closure rates exceeding 90%. The prognostic factors influencing visual [...] Read more.
Background/Objectives: A macular hole represents a significant surgical condition in an increasingly aging population. Advances in surgical techniques, particularly pars plana vitrectomy with inverted internal limiting membrane (ILM) flap, have established high anatomical closure rates exceeding 90%. The prognostic factors influencing visual recovery remain incompletely understood, and it is unclear which patients can be expected to achieve optimal functional outcomes. Methods: This retrospective longitudinal study included 35 eyes of 32 patients followed for 3–12 months. Preoperative OCT parameters (minimum linear diameter, basal diameter, and hole height) and derived indices were correlated with functional outcomes, including best-corrected visual acuity (BCVA) and microperimetry, stratified as central macular sensitivity (CMS) and sensitivity at 4° and 20°. Postoperative ellipsoid zone (EZ) and external limiting membrane (ELM) integrity were also analyzed. Predictive performance was assessed using root mean square error (RMSE) and coefficient of determination (R2). A linear regression model based on BCVA served as baseline, while Extreme Gradient Boosting (XGBoost) models incorporating OCT features were developed. Feature importance was evaluated using Shapley Additive Explanations (SHAP). Results: Overall closure rate was 100%, including 91.4% Type 1 and 8.6% Type 2 closure. Models incorporating OCT parameters outperformed BCVA-based models (lower RMSE, and higher R2). Minimum linear diameter and hole height were the strongest predictors of postoperative outcomes. Microperimetry detected functional improvement beyond BCVA and correlated with EZ and ELM restoration. Conclusions: Preoperative macular hole morphology represents a key determinant of postoperative functional recovery. These structural parameters provide meaningful prognostic value beyond visual acuity alone, supporting the role of combined OCT and microperimetric assessment in predicting surgical outcomes. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 4th Edition)
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Review

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19 pages, 975 KB  
Review
Plasma Citrulline as a Biomarker in Critical Illness: A Structured Narrative Review
by Oana Frandeș, Alexandra Elena Lazăr, Sergiu Ioan Frandeș, Oana Elena Branea and Leonard Azamfirei
Diagnostics 2026, 16(17), 2831; https://doi.org/10.3390/diagnostics16172831 - 2 Sep 2026
Viewed by 178
Abstract
Introduction: Gastrointestinal dysfunction is common in critically ill patients and is associated with increased morbidity and mortality. Plasma citrulline, a non-proteinogenic amino acid synthesized by enterocytes, has been proposed as a biomarker of intestinal function and enterocyte mass. However, the available evidence [...] Read more.
Introduction: Gastrointestinal dysfunction is common in critically ill patients and is associated with increased morbidity and mortality. Plasma citrulline, a non-proteinogenic amino acid synthesized by enterocytes, has been proposed as a biomarker of intestinal function and enterocyte mass. However, the available evidence regarding its clinical significance in critically ill patients remains heterogeneous. This structured narrative review aimed to evaluate the current evidence on plasma citrulline in critical illness, focusing on its association with gastrointestinal dysfunction, disease severity, and clinical outcomes. Methods: A structured narrative review based on a structured literature search was conducted using PubMed and Scopus. Reference lists of included studies and relevant reviews were also screened. Studies evaluating circulating citrulline in adult critically ill patients and reporting gastrointestinal dysfunction, intestinal injury, disease severity, or other relevant clinical outcomes were included. Study selection was performed by two reviewers, and data were analyzed descriptively. Results: Eleven studies met the inclusion criteria, the majority being prospective observational studies. The timing of citrulline measurement, patient populations, analytical methods, and evaluated outcomes varied considerably across studies. Lower circulating citrulline concentrations were frequently associated with gastrointestinal dysfunction or markers of intestinal impairment; however, associations with disease severity, mortality, and other clinical outcomes were inconsistent. Several factors, including renal function, systemic inflammation, and methodological variability, may influence the interpretation of circulating citrulline concentrations. Conclusions: Plasma citrulline may provide complementary information regarding enterocyte function and gastrointestinal dysfunction in critically ill patients. However, current evidence does not support its use as a standalone diagnostic or prognostic biomarker. Further prospective studies using standardized measurement protocols and serial assessment are needed to determine its potential role alongside clinical evaluation and complementary biomarkers. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 4th Edition)
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