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23 pages, 2591 KB  
Article
Post-Chemotherapy Changes and Agreement of CT-Derived Body Composition at L3 and T12 in Older Patients with Metastatic Colorectal Cancer: Associations with Nutritional Indices and Outcomes
by Anıl Yıldız, Melin Aydan Ahmed, Nihan Nizam Eren, Abdulmunir Azizy, Selay Artan, Simay Çokgezer, Bedirhan Ulufer, Ozan Deniz Aygörmez, Gündüz Karaoğlan, Şirin Zelal Şahin Tırnova, Gulistan Bahat, Mustafa Durmaz, İnci Kızıldağ Yırgın, Senem Karabulut, Burak Sakar, Mehmet Akif Karan and Didem Taştekin
Nutrients 2026, 18(7), 1090; https://doi.org/10.3390/nu18071090 (registering DOI) - 28 Mar 2026
Abstract
Background: Age- and cancer-related sarcopenia and malnutrition are common in older patients with colorectal cancer (CRC) and may negatively influence treatment tolerance and prognosis. However, the comparative prognostic value of post-chemotherapy changes in CT-based body composition parameters at the third lumbar vertebra (L3) [...] Read more.
Background: Age- and cancer-related sarcopenia and malnutrition are common in older patients with colorectal cancer (CRC) and may negatively influence treatment tolerance and prognosis. However, the comparative prognostic value of post-chemotherapy changes in CT-based body composition parameters at the third lumbar vertebra (L3) and the twelfth thoracic vertebra (T12) levels, and their associations with nutritional indices, remain unclear. This study aimed to examine and compare the prognostic relevance of post-chemotherapy body composition changes at L3 and T12 and to assess their relationship with nutritional indices in older patients with metastatic CRC (mCRC). Methods: This retrospective study included 87 older patients with mCRC. Baseline and ~3-month follow-up CT scans were analyzed at L3 and T12 using 3D Slicer to quantify skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), visceral-to-subcutaneous fat ratio (VSR), and intramuscular adipose tissue index (IMATI). Changes (Δ) in CT-derived body composition after chemotherapy were calculated as percentage change using ((follow-up − baseline)/baseline) × 100. Prognostic Nutritional Index (PNI) and Geriatric Nutritional Index (GNRI), which are established nutritional assessment tools, were calculated from baseline laboratory/anthropometric data. Agreement between T12 and L3 was assessed, and associations with grade ≥3 toxicity, progression-free survival (PFS), and overall survival (OS) were evaluated using multivariable models and ROC analyses. Results: Mean age was 69.0 ± 4.5 years (59 male/28 female), and 26.4% developed grade ≥3 adverse events. Over 3 months, mean SMI declined significantly at both L3 (46.7 ± 8.8 → 42.8 ± 9.8 cm2/m2) and T12 (34.6 ± 8.2 → 31.6 ± 8.1 cm2/m2) (p < 0.001 for both), accompanied by decreases in VATI and VSR; T12-IMATI increased significantly. Baseline PNI showed a weak positive correlation with L3-SMI (r = 0.302, p = 0.033), whereas GNRI showed moderate correlations with SMI at L3 (r = 0.502, p < 0.001) and T12 (r = 0.317, p = 0.025) and was associated with longitudinal changes in muscle metrics. T12-SMI consistently yielded lower values than L3-SMI, and agreement varied by compartment (best for SATI; weakest for VSR). Lower GNRI and greater L3-SMI loss were independently associated with grade ≥3 toxicity; ΔL3-SMI showed the highest discrimination (AUC = 0.79, 95% CI = 0.69–0.87, p < 0.001; cut-off >5.1% loss). All patients progressed (median PFS 7.6 months); mortality was 82.8% (median follow-up: 25 months). In multivariable analysis, PFS, CRP, GNRI, and ΔL3-SMI remained independently associated with OS. ΔL3-SMI provided the strongest mortality discrimination (AUC = 0.85, 95% CI = 0.74–0.94, p < 0.001; cut-off >10.4% loss), while ΔIMATI was also informative (AUC = 0.71, 95% CI = 0.59–0.82, p = 0.023). Conclusions: In older patients with mCRC, early post-chemotherapy skeletal muscle loss—particularly at the L3 level—showed the strongest prognostic association with severe toxicity and mortality. GNRI provided complementary prognostic information as a marker of baseline immunonutritional reserve. Although T12-derived measurements were correlated with L3-derived values, systematic bias suggests that they should not be interpreted interchangeably for longitudinal risk stratification. Full article
(This article belongs to the Special Issue Nutrition and Dietary Guidelines for Colorectal Cancer Patients)
12 pages, 1315 KB  
Article
Feasibility of TP53-Mutated ctDNA Monitoring in High-Grade Endometrial Cancer Using Routine NGS
by Regine Marlin, Mehdi Jean-Laurent, Clarisse Joachim, Alexis Vallard, Sabrina Pennont, Valerie Suez-Panama, Mickaelle Rose, Sylviane Ulric-Gervaise, Sylvie Lusbec, Odile Bera, Aude Aline-Fardin and Coralie Ebring
Cancers 2026, 18(7), 1102; https://doi.org/10.3390/cancers18071102 (registering DOI) - 28 Mar 2026
Abstract
Background/Objectives: High-grade endometrial cancer (EC) is associated with poor outcomes, particularly in populations with a high burden of aggressive histologies. There is a critical need for accessible biomarkers to improve prognostic assessment and guide clinical management. Methods: In this study, we evaluated the [...] Read more.
Background/Objectives: High-grade endometrial cancer (EC) is associated with poor outcomes, particularly in populations with a high burden of aggressive histologies. There is a critical need for accessible biomarkers to improve prognostic assessment and guide clinical management. Methods: In this study, we evaluated the feasibility and clinical relevance of monitoring circulating tumor DNA (ctDNA) by tracking somatic TP53 mutations using a routine next-generation sequencing (NGS) assay already implemented in diagnostic practice. Results: Among 21 patients with high-grade EC carrying TP53 mutations in the primary tumor, ctDNA was detectable in over 75% during follow-up. Baseline ctDNA detection strongly correlated with advanced disease: none of the FIGO I tumors were ctDNA-positive at diagnosis, whereas 73% of FIGO > I tumors showed detectable ctDNA. Patients with ctDNA detected at baseline had significantly poorer outcomes, with a 2-year recurrence-free survival (RFS) of 18% versus 60% and a 2-year overall survival (OS) of 40% versus 78%. Longitudinal monitoring revealed that postoperative persistence or reappearance of ctDNA was consistently associated with disease progression, often preceding radiological relapse. Conversely, early ctDNA clearance (at M4–M8) was associated with more favorable clinical trajectories. Conclusions: These findings highlight the potential role of ctDNA as a real-time molecular marker of minimal residual disease and tumor dynamics. Our results demonstrate that TP53-based ctDNA tracking using a standard NGS panel is feasible, sensitive, and clinically informative in high-grade EC. This approach may contribute to improving prognostic stratification and enabling more personalized, responsive clinical management, particularly in high-risk populations. Full article
(This article belongs to the Section Cancer Biomarkers)
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18 pages, 2681 KB  
Article
Identification of a Novel Disulfidptosis-Related Five-Gene Signature for Prognostic Prediction and Immune Characterization in Esophageal Cancer
by Yiru Chen, Xuefeng Li, Hui Jiang, Xiaohui Liu, Nan Ma and Xuemei Wang
Biology 2026, 15(7), 545; https://doi.org/10.3390/biology15070545 (registering DOI) - 28 Mar 2026
Abstract
Esophageal cancer is a highly aggressive malignancy with a poor prognosis. More precise prognostic biomarkers are therefore needed. Disulfidptosis is a recently identified form of regulated cell death driven by disulfide stress. It has been implicated in tumor progression. However, its prognostic role [...] Read more.
Esophageal cancer is a highly aggressive malignancy with a poor prognosis. More precise prognostic biomarkers are therefore needed. Disulfidptosis is a recently identified form of regulated cell death driven by disulfide stress. It has been implicated in tumor progression. However, its prognostic role in esophageal cancer remains largely unexplored. This study aimed to develop a disulfidptosis-related gene signature for risk stratification and outcome prediction in esophageal cancer patients. Based on 23 disulfidptosis-related genes, consensus clustering was performed to identify molecular subtypes. Differentially expressed genes (DEGs) between subtypes were subjected to functional enrichment, immune microenvironment, and drug sensitivity analyses. Univariate and multivariate Cox regression were used to construct a prognostic risk model, which was evaluated using time-dependent receiver operating characteristic (ROC) curve and Kaplan–Meier analysis. A clinical nomogram integrating the risk score and clinicopathological factors was developed and validated. Two distinct disulfidptosis-related subtypes were identified, showing significant differences in gene expression, immune infiltration, and stromal scores. A total of 1080 DEGs were enriched in pathways related to epidermal differentiation, NRF2 signaling, and glucocorticoid receptor activity. A five-gene prognostic signature was established and effectively stratified patients into high- and low-risk groups. The risk model exhibited strong discrimination for 1-, 3-, and 5-year overall survival outcomes. The predictive accuracy was further maximized through an integrated clinical nomogram, which achieved an outstanding area under the curve (AUC) of 0.94 for 5-year survival predictions. Drug sensitivity analysis revealed subtype-specific therapeutic vulnerabilities, supporting potential precision treatment strategies. This study proposes a novel disulfidptosis-related five-gene signature and nomogram that robustly predict prognosis in esophageal cancer. The findings highlight the clinical relevance of disulfidptosis in tumor biology and offer a potential tool for risk stratification and personalized therapeutic decision-making. Full article
(This article belongs to the Special Issue Current Advances in Cancer Genomics)
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14 pages, 1604 KB  
Article
Reassessment of Lymphovascular Invasion and Its Subtypes as Predictors of Prognosis and Recurrence in Gastric Cancer Using an Enhanced Detection Method
by Jingdong Liu, Changle Yang, Bosen Li, Zhaodong Sun, Dan Liu, Xinyou Liu, Hao Chen, Jie Sun, Haojie Li, Yihong Sun, Junjie Zhao and Xuefei Wang
Cancers 2026, 18(7), 1101; https://doi.org/10.3390/cancers18071101 (registering DOI) - 28 Mar 2026
Abstract
Background and Aim: Lymphovascular invasion (LVI) is a negative prognostic factor for gastric cancer, but detection limitations hinder its clinical utility and subtype analysis. This study aimed to explore the predictive value of LVI and its subtypes in the prognosis and recurrence patterns [...] Read more.
Background and Aim: Lymphovascular invasion (LVI) is a negative prognostic factor for gastric cancer, but detection limitations hinder its clinical utility and subtype analysis. This study aimed to explore the predictive value of LVI and its subtypes in the prognosis and recurrence patterns of gastric cancer using our enhanced detection method. Methods: We reviewed 2057 patients who underwent gastrectomy in 2018, of whom 1073 met the inclusion criteria. Propensity score matching (PSM) was performed to balance baseline clinicopathological characteristics. Results: After PSM, 311 patients were assigned to the LVI+ group and 311 to the LVI- group. The LVI+ group demonstrated a poorer prognosis. Subtype analysis revealed that lymphatic invasion (LI), but not venous invasion (VI), was associated with poor prognosis in the matched cohort. Stratified by pathological tumor-node-metastasis (TNM) stage, LVI+ and LI+ patients had worse prognosis in Stages I and III, while VI+ patients had worse prognosis in Stage III. Stratified by lymph node status, LVI+ predicted poorer prognosis in both node-negative (N0) and node-positive (N+) patients, and LI+ was also associated with worse prognosis among N+ patients, whereas VI+ was not significantly associated with prognosis in either subgroup. Recurrence analysis indicated that LVI+ was associated with distant and peritoneal metastases, whereas LI+ was associated with local recurrence, distant and peritoneal metastases. Conclusions: Lymphovascular invasion was associated with adverse prognosis in resectable gastric cancer, with lymphatic invasion showing a stronger prognostic impact than venous invasion. These findings indicate that refined assessment of lymphovascular invasion may complement conventional TNM staging in postoperative risk stratification. Full article
(This article belongs to the Section Clinical Research of Cancer)
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34 pages, 900 KB  
Review
The Role of Serum Biomarkers for the Differential Diagnosis and Prognostic Assessment of Myocardial Infarction with Non-Obstructive Coronary Arteries: A Narrative Review
by Matteo Orlandi, Ruggero Mazzotta, Niccolò Ciardetti, Giorgia Panichella, Manuel Garofalo, Lucrezia Biagiotti, Maria Federica Crociani, Samuele Salvi, Carlo Di Mario, Francesco Meucci and Alessio Mattesini
J. Clin. Med. 2026, 15(7), 2593; https://doi.org/10.3390/jcm15072593 (registering DOI) - 28 Mar 2026
Abstract
Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical entity encompassing multiple ischemic mechanisms, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction, coronary embolism, and spontaneous coronary artery dissection. Despite the absence of obstructive coronary disease, patients with MINOCA [...] Read more.
Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical entity encompassing multiple ischemic mechanisms, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction, coronary embolism, and spontaneous coronary artery dissection. Despite the absence of obstructive coronary disease, patients with MINOCA remain at substantial risk of adverse cardiovascular outcomes, underscoring the need for accurate early diagnosis and effective risk stratification. In this context, accumulating evidence indicates that circulating serum biomarkers may provide additional pathophysiological and prognostic insights in patients with a working diagnosis of MINOCA. Moreover, distinct biomarker profiles may help support the differential diagnostic evaluation between MINOCA and other causes of acute myocardial injury, such as myocardial infarction with obstructive coronary arteries, myocarditis, and Takotsubo syndrome. This narrative review summarizes current evidence on serum biomarkers in MINOCA, highlights their potential role in guiding tailored diagnostic strategies, and discusses future perspectives toward biomarker-driven precision medicine in patients presenting with acute myocardial injury. Full article
(This article belongs to the Special Issue The Role of Biomarkers in Cardiovascular Diseases)
21 pages, 1435 KB  
Article
Growth Differentiation Factor 15 as a Biomarker of Cardiovascular Burden and Mortality in a Population-Based Cohort
by Beatriz Martín-Carro, Leticia Nieto-García, Clara Sánchez-Pablo, Alfonso Romero, Candelas Pérez del Villar, José Carlos Moyano-Maza, José María de Dios, David Cembrero-Fuciños, Estefanía Iglesias-Colino, Paz Muriel, Sara Cascón, Amalia Martín-Gallego, Baltasara Blázquez, Inmaculada Santolino, Lydia González-González, María Concepción Ledesma, Javier Maillo-Seco, Jesús Rodríguez-Nieto, Luis M. Rincón, María Isidoro-García and Pedro L Sánchezadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2026, 27(7), 3078; https://doi.org/10.3390/ijms27073078 (registering DOI) - 27 Mar 2026
Abstract
Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine strongly associated with aging, multimorbidity, and cardiovascular disease. Although prior studies have established its prognostic value in high-risk populations, its role in the general population remains less defined. The aim of this study was [...] Read more.
Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine strongly associated with aging, multimorbidity, and cardiovascular disease. Although prior studies have established its prognostic value in high-risk populations, its role in the general population remains less defined. The aim of this study was to determine if there is an association between plasma GDF15 levels, heart disease and mortality in a representative population-based cohort. We analyzed 1532 participants (mean age 55 years; 54.6% women) with available baseline plasma GDF15 concentrations. Participants were stratified according to an optimal cutoff of 1081 pg/mL, derived from ROC curve analysis for mortality. Associations with prevalent heart disease were assessed using multivariable logistic regression models adjusted for cardiovascular risk factors and NT-proBNP. Mortality was analyzed using Cox proportional hazards models, with model performance evaluated by C-index and time-dependent ROC curves. Individuals with GDF15 > 1081 pg/mL were older and exhibited a more adverse cardiometabolic profile with higher prevalence of comorbidities. Elevated GDF15 was independently associated with ischemic cardiomyopathy (OR 3.34, 95% CI: 1.38–8.11), particularly in men (OR 4.26, 95% CI: 1.40–12.96), but not in women. No independent associations were observed with arrhythmias, valvulopathy, or heart failure after adjustment for NT-proBNP. During a median follow-up of 6.2 years, 51 deaths occurred. Elevated GDF15 independently predicted all-cause mortality (HR 2.47, 95% CI: 1.19–5.13), though the effect was attenuated after adjustment for NT-proBNP. GDF15 improved model discrimination (ΔC-index = +0.01; LRT p = 0.011) and showed robust time-dependent predictive ability, with AUCs of 0.76, 0.82, and 0.85 at 2, 4, and 6 years, respectively. In this population-based cohort, elevated GDF15 identified individuals with an adverse health profile, was independently associated with ischemic cardiomyopathy in men, and predicted mortality. Although its incremental predictive value over NT-proBNP was modest, GDF15 could provide complementary biological information and may enhance multimarker strategies for cardiovascular risk stratification in the general population. Full article
12 pages, 276 KB  
Article
Development of an Enomogram to Predict the Rate of Loco-Regional Control After Radio-Chemotherapy and Interventional Radiotherapy in Cervical Cancer
by Valentina Lancellotta, Maria Concetta La Milia, Rosa Autorino, Enrico Rosa, Bruno Fionda, Pierpaolo Dragonetti, Leonardo Bannoni, Raffaella Michela Rinaldi, Viola De Luca, Gerardina Stimato, Angeles Rovirosa, Alessio Giuseppe Morganti, Gabriella Macchia, Benedetta Gui, Nicolò Bizzarri, Anna Fagotti, Luca Tagliaferri and Maria Antonietta Gambacorta
Cancers 2026, 18(7), 1096; https://doi.org/10.3390/cancers18071096 - 27 Mar 2026
Abstract
Objective: This study aimed to explore the association between magnetic resonance imaging (MRI)-derived volumetric parameters and oncological outcomes, and to develop an exploratory predictive model based on these variables in patients treated with radio-chemotherapy followed by interventional radiotherapy (modern brachytherapy). Methods: [...] Read more.
Objective: This study aimed to explore the association between magnetic resonance imaging (MRI)-derived volumetric parameters and oncological outcomes, and to develop an exploratory predictive model based on these variables in patients treated with radio-chemotherapy followed by interventional radiotherapy (modern brachytherapy). Methods: Between 2021 and 2024, 300 patients with cervical cancer were included. Treatment was pelvic external beam radiotherapy with platinum-based chemotherapy followed by interventional radiotherapy boost. Volumetric MRI variables for each patient were collected. Time-to-event analyses were performed using Cox proportional hazards regression models. Model performance was assessed using Harrell’s concordance index (C-index). Internal validation was performed using bootstrap resampling. Based on the final multivariable Cox models, an interactive web-based nomogram was developed as an exploratory tool to visualize model-derived associations. Results: Median tumor volume decreased from 69.4 cm3 at diagnosis to 2.2 cm3 at the time of pre-interventional radiotherapy MRI, with a median reduction rate of 96.5%. Tumor volume at diagnosis, pre-interventional radiotherapy residual tumor volume, and tumor volume reduction rate were significantly associated with loco-regional relapse and distant metastases in Cox regression analyses. These findings were consistent across univariate and multivariable models. Internal validation confirmed the stability of the model estimates. Conclusions: MRI-derived volumetric parameters are associated with oncological outcomes in patients with locally advanced cervical cancer and may contribute to early risk stratification. The proposed model should be considered exploratory and hypothesis-generating and requires external validation before any potential clinical application. Full article
(This article belongs to the Special Issue Brachytherapy in the Treatment of Gynaecological Malignancies)
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25 pages, 4104 KB  
Article
Prediction of Postoperative Stroke in Elderly Surgical ICU Patients Using Random Forest Model: Development on MIMIC-IV with Cross-Institutional and Temporal External Validation
by Houji Jin, Mohammadsaeed Haghi, Nausin Kudrot, Kamiar Alaei and Maryam Pishgar
BioMedInformatics 2026, 6(2), 16; https://doi.org/10.3390/biomedinformatics6020016 - 27 Mar 2026
Abstract
Postoperative stroke is a serious and fatal condition that often affects elderly surgical patients. This rare but severe complication arises from complex interactions between comorbidities, physiologic instability and demographic disturbances that traditional risk tools often fail to capture.This study aims to develop and [...] Read more.
Postoperative stroke is a serious and fatal condition that often affects elderly surgical patients. This rare but severe complication arises from complex interactions between comorbidities, physiologic instability and demographic disturbances that traditional risk tools often fail to capture.This study aims to develop and validate a machine learning model with an improved ability to predict the risk of postoperative stroke in elderly patients utilising the comprehensive clinical and demographic ICU data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. External validation was performed on MIMIC-III and the eICU Collaborative Research Database, with eICU being the primary validation set. We identified postoperative surgical intensive care unit (SICU) patients aged 55 years or older from all databases. A strict temporal window of the first 24 h of ICU admission was applied across all three datasets while extracting features like laboratory measurements and vital sign summaries in order to ensure that all predictor values were derived from a fixed observation period at the beginning of ICU stay. After preprocessing, applying Multivariate Imputation by Chained Equations (MICE) imputation and initial screening of 88 candidate variables, 20 clinically meaningful predictors were selected through a multistage feature selection pipeline incorporating RFECV and permutation importance. SHAP analysis and LIME analysis were used for interpretability. We evaluated ten machine learning techniques, including Logistic Regression, Decision Tree, Random Forest, K-Nearest Neighbors (KNNs), Support Vector Machine (SVM–RBF Kernel), Gradient Boosting (GBDT), Neural Network, XGBoost, CatBoost, Naive Bayes. Among them, Random Forest demonstrated strong predictive performance by achieving an AUROC of 0.8072 (95% CI [0.7890, 0.8253]) on the internal validation set. The model also achieved AUROC of 0.7557 (95% CI [0.7267, 0.7794]) and 0.9144 (95% CI [0.8893, 0.9378]) on the external validation sets eICU and MIMIC-III, respectively. Mean systolic blood pressure, Elixhauser score, minimum calcium, and minimum INR (PT) were consistently identified as the most influential predictors through both SHAP analysis and LIME analysis, thus strengthening model interpretability. Our findings suggest that a Random Forest-based predictive model can provide an accurate and generalisable prediction of postoperative stroke in elderly ICU patients using routinely collected physiologic and laboratory data. This also supports early risk stratification and targeted postoperative monitoring. Full article
(This article belongs to the Section Applied Biomedical Data Science)
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22 pages, 632 KB  
Review
Oxidative Stress in Diabetic Retinopathy: Pathogenic Mechanisms, Biomarkers and Clinical Implications
by Caterina Toma, Diego Ferdeghini, Mohammad Mostafa Ola Pour, Sakthipriyan Venkatesan, Stefano De Cillà and Elena Grossini
Antioxidants 2026, 15(4), 425; https://doi.org/10.3390/antiox15040425 - 27 Mar 2026
Abstract
Diabetic retinopathy (DR) is a leading cause of vision loss worldwide and represents a complex neurovascular complication of diabetes mellitus driven by chronic hyperglycemia. Increasing evidence identifies oxidative stress—defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—as a central [...] Read more.
Diabetic retinopathy (DR) is a leading cause of vision loss worldwide and represents a complex neurovascular complication of diabetes mellitus driven by chronic hyperglycemia. Increasing evidence identifies oxidative stress—defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—as a central pathogenic mechanism linking metabolic dysregulation to retinal injury. The retina is particularly vulnerable to oxidative damage due to its high metabolic demand, elevated oxygen consumption, and abundance of polyunsaturated fatty acids. Hyperglycemia activates multiple interconnected biochemical pathways, including the polyol and hexosamine pathways, protein kinase C signaling, advanced glycation end-product formation, and lipid peroxidation, all of which converge on excessive ROS production and mitochondrial dysfunction. Growing attention has focused on oxidative stress biomarkers as tools to characterize DR severity and progression. Elevated systemic markers of lipid, protein, and DNA oxidation, together with impaired antioxidant capacity, correlate with disease stage, while oxidative biomarkers detected in aqueous and vitreous humor reflect localized retinal injury. Importantly, oxidative stress biomarkers are also associated with functional outcomes, including best-corrected visual acuity and diabetic macular edema. Integration of systemic and ocular oxidative biomarkers with clinical staging may improve risk stratification and support personalized therapeutic strategies in DR. Full article
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25 pages, 799 KB  
Review
HPV Detection in Oropharyngeal Cancer: A Narrative Review of Diagnostic and Emerging Molecular Approaches
by Fernando López, Remco de Bree, M. P. Sreeram, Sandra Nuyts, Juan Pablo Rodrigo, Karthik N. Rao, Nabil F. Saba, Carol Bradford, Arlene Forastiere, Luiz P. Kowalski, Anna Luíza Damaceno Araújo, Carlos Suarez and Alfio Ferlito
Diagnostics 2026, 16(7), 1010; https://doi.org/10.3390/diagnostics16071010 - 27 Mar 2026
Abstract
Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite [...] Read more.
Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite advances, substantial variability persists among diagnostic methods and clinical workflows. A narrative review of PubMed, Scopus, and Web of Science databases was conducted up to July 2025. Studies addressing HPV detection techniques in OPSCC—including p16^INK4a^ immunohistochemistry (IHC), HPV DNA and RNA assays, liquid biopsy approaches, and computational surrogates—were critically analyzed regarding diagnostic accuracy, clinical applicability, and emerging innovations. Tissue-based assays remain the diagnostic reference standard. p16 IHC provides high sensitivity but limited specificity and should be confirmed with nucleic acid-based methods such as DNA PCR, in situ hybridization (ISH), or E6/E7 mRNA detection. Combined or “orthogonal” testing minimizes discordance and refines risk stratification. Liquid biopsy detection of circulating HPV DNA using droplet digital PCR or next-generation sequencing has shown high sensitivity and specificity in cohorts of patients with HPV-associated OPSCC, supporting its potential role as a complementary biomarker for treatment monitoring and surveillance. However, circulating HPV DNA alone does not unequivocally identify the anatomic source of HPV DNA and should be interpreted together with clinical, radiologic, and tissue-based findings. Oral rinse and saliva assays show moderate diagnostic performance, while artificial intelligence-based radiomic and histopathologic models are emerging as complementary tools. Reliable HPV attribution in OPSCC requires a multimodal diagnostic strategy integrating p16 IHC, molecular confirmation, and ctHPV-DNA monitoring. Methodological standardization and prospective validation are essential to implement precision-guided, cost-effective workflows in routine clinical practice. Full article
(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)
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14 pages, 551 KB  
Review
Ultrasound Elastography for the Assessment of Sarcopenia
by Chenzi Zhang and Lin Kang
J. Clin. Med. 2026, 15(7), 2566; https://doi.org/10.3390/jcm15072566 - 27 Mar 2026
Abstract
Background: Sarcopenia is an age-related syndrome characterized by progressive loss of skeletal muscle mass and strength, representing a major contributor to disability and increased mortality in older adults. Current diagnostic frameworks increasingly emphasize muscle quality alongside quantity, creating a clinical need for [...] Read more.
Background: Sarcopenia is an age-related syndrome characterized by progressive loss of skeletal muscle mass and strength, representing a major contributor to disability and increased mortality in older adults. Current diagnostic frameworks increasingly emphasize muscle quality alongside quantity, creating a clinical need for bedside tools that can objectively assess muscle mechanical properties. Shear-wave elastography (SWE), an ultrasound-based technique that quantifies muscle stiffness, has emerged as a promising biomechanical biomarker of muscle quality. Aim: This narrative review evaluates the evidence supporting SWE for assessing muscle quality and its association with aging, sarcopenia, and functional outcomes. Methods: We searched PubMed, Embase, and Web of Science (from January 2010 to December 2025) using terms related to elastography and sarcopenia. Based on relevance and methodological quality, approximately 50 key studies were selected for in-depth discussion and synthesis. Synthesis: Observational studies consistently demonstrate that SWE detects age-related reductions in muscle stiffness, which correlate significantly with declines in muscle strength and physical performance. Unlike conventional B-mode ultrasound, which primarily provides morphological parameters, SWE directly reflects intrinsic tissue mechanics, enabling more direct assessment of muscle quality. In high-risk populations such as patients with type 2 diabetes, reduced muscle stiffness is also associated with sarcopenia and poor functional outcomes. However, reported stiffness trends with aging remain heterogeneous, and validated diagnostic thresholds are lacking. Stiffness changes vary by muscle group, acquisition protocol, and loading state. Clinical implementation is currently limited by inter-device variability, operator dependence, and sensitivity to muscle loading conditions. Conclusions: Current evidence suggests that SWE holds promise as an adjunctive research tool for assessing muscle quality and risk stratification, but it is not yet ready for standalone clinical diagnosis due to methodological heterogeneity, lack of validated cutoffs, and limited longitudinal data. Future large-scale, longitudinal, multicenter studies with standardized protocols are needed to establish its definitive diagnostic utility. Full article
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13 pages, 529 KB  
Review
Dynamics of 1,3-β-D-Glucan in Invasive Candidiasis: A Narrative Review of Microbiological Aspects and Diagnostic Implications
by Maddalena Calvo, Marta Caccamo, Dalila Maria Cammarata and Laura Trovato
Antibodies 2026, 15(2), 28; https://doi.org/10.3390/antib15020028 - 27 Mar 2026
Abstract
Invasive candidiasis (IC) remains a significant cause of morbidity and mortality among critically ill, hematologic, and neonatal patients worldwide. Rapid and accurate diagnosis is essential to guide timely antifungal therapy and improve outcomes. Among available diagnostic tools, 1,3-β-D-glucan (BDG), a polysaccharide component of [...] Read more.
Invasive candidiasis (IC) remains a significant cause of morbidity and mortality among critically ill, hematologic, and neonatal patients worldwide. Rapid and accurate diagnosis is essential to guide timely antifungal therapy and improve outcomes. Among available diagnostic tools, 1,3-β-D-glucan (BDG), a polysaccharide component of the fungal cell wall, has emerged as a key biomarker. BDG assays allow for early detection of probable IC, often preceding positive blood cultures, and offer prognostic information based on serial measurements. Species-specific differences in Candida cell wall composition influence BDG release and diagnostic sensitivity. Candida albicans generally correlates with high BDG levels, whereas Nakaseomyces glabrata, Candida parapsilosis, and Candida auris exhibit variable or lower glucan exposure, limiting assay sensitivity. BDG performance is affected by patient-specific factors, such as prior surgery, transfusions, or coexisting bacterial infections, which may lead to false-positive results. Molecular techniques, including PCR-based assays, provide complementary diagnostic accuracy and species identification, and their combination with BDG testing enhances sensitivity up to 90%. Serial BDG monitoring supports risk stratification and treatment response assessment, with persistent elevations predicting worse outcomes. In neonatal and pediatric populations, optimal cut-off values remain under investigation, highlighting the need for integration with clinical and microbiological data. Overall, BDG represents a valuable adjunct in a multimodal diagnostic workflow, providing both diagnostic and prognostic insights in invasive candidiasis management. Full article
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11 pages, 239 KB  
Article
Early Vascular Aging and Subclinical Myocardial Deformation in Children with β-Thalassemia Major: The Role of Asymmetric Dimethylarginine
by Pelin Kosger, Zeynep Canan Özdemir, Ayse Sulu, Özcan Bör and Birsen Uçar
Children 2026, 13(4), 461; https://doi.org/10.3390/children13040461 - 27 Mar 2026
Abstract
Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular [...] Read more.
Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular aging, yet their impact on myocardial deformation in pediatric patients remains incompletely characterized. Objectives: To evaluate subclinical myocardial dysfunction and arterial stiffness in children with β-TM and to investigate hemolysis-related changes in asymmetric dimethylarginine (ADMA) and L-arginine as biomarkers of endothelial dysfunction in relation to cardiovascular involvement. Methods: Twenty-four children with β-TM and 20 age-matched healthy controls were included. Cardiac structure and myocardial deformation were assessed by conventional echocardiography, tissue Doppler imaging, and speckle-tracking strain analysis. Arterial stiffness was evaluated using oscillometric pulse wave analysis and bilateral carotid intima–media thickness (CIMT). Serum ADMA and L-arginine levels were measured, and hemoglobin, reticulocyte count, and ferritin levels were recorded. Results: Children with β-thalassemia major demonstrated significantly increased arterial stiffness compared with controls, including higher PWV (4.61 ± 0.37 vs. 4.38 ± 0.31), AIx@75 (augmentation index at 75 bpm) (28.5 ± 8.34 vs. 22.8 ± 6.51), left CIMT [0.45 (0.39–0.51) vs. 0.41 (0.38–0.46)], and right CIMT [0.43 (0.39–0.54) vs. 0.40 (0.34–0.46)]. In addition, patients exhibited reduced global longitudinal strain (−19.3 ± 2.91 vs. −21.84 ± 1.91), prolonged isovolumetric relaxation time [53 (37–71) vs. 45 (37–55)], and elevated E/Em (8.44 ± 2.19 vs. 6.92 ± 1.10). ADMA levels were significantly higher in patients (0.54 ± 0.19 vs. 0.39 ± 0.22) and were positively associated with reticulocyte counts and inversely correlated with hemoglobin levels. In addition, both ADMA and ferritin levels were positively correlated with arterial stiffness indices and left ventricular filling pressures. Conclusions: Children with β-thalassemia major exhibit features suggestive of early cardiovascular aging, including impaired myocardial deformation, diastolic involvement, and increased arterial stiffness. The observed association between ADMA levels and markers of hemolysis, vascular stiffness, and myocardial deformation highlights the potential involvement of endothelial dysfunction in premature myocardial–vascular remodeling. These findings suggest that ADMA may serve as a promising biomarker for early cardiovascular risk in pediatric β-thalassemia major; however, further longitudinal and multi-center studies are needed to confirm its clinical utility for risk stratification. Full article
(This article belongs to the Section Pediatric Cardiology)
19 pages, 695 KB  
Review
How to Change the Role of Allogeneic Hematopoietic Cell Transplantation in Adults with B-Cell Acute Lymphoblastic Leukemia
by Martina Canichella and Paolo de Fabritiis
Curr. Issues Mol. Biol. 2026, 48(4), 351; https://doi.org/10.3390/cimb48040351 - 27 Mar 2026
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has long constituted a cornerstone of post-remission consolidation therapy for adults with high-risk B-cell acute lymphoblastic leukemia (B-ALL), offering potent graft-versus-leukemia activity at the expense of significant treatment-related toxicity (TRT) and non-relapse mortality (NRM). Over the past [...] Read more.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has long constituted a cornerstone of post-remission consolidation therapy for adults with high-risk B-cell acute lymphoblastic leukemia (B-ALL), offering potent graft-versus-leukemia activity at the expense of significant treatment-related toxicity (TRT) and non-relapse mortality (NRM). Over the past two decades, however, outcomes following allo-HSCT have improved substantially. This progress has been driven primarily by a marked reduction in NRM, translating into improved overall survival (OS), as consistently documented by large cooperative group analyses and single-center series. Advances in supportive care, infectious prophylaxis, donor selection, and graft-versus-host disease (GvHD) prevention have contributed substantially to this improvement. In parallel, transplant decision-making has been profoundly reshaped by refined disease biology-based risk stratification and the systematic evaluation of measurable residual disease (MRD). Moreover, the advent of highly effective immunotherapeutic approaches—including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapies—has enabled the achievement of deeper molecular remissions prior to transplantation, both in first and subsequent complete remissions. Taken together, these developments have shifted allo-HSCT from a widely applied strategy to a more individualized, risk-adapted therapeutic approach. This review examines how the indications, timing, and objectives of allo-HSCT are evolving in the contemporary treatment landscape of adult B-ALL, with particular emphasis on Philadelphia chromosome–negative, Philadelphia-like, and Philadelphia chromosome–positive disease subsets. Full article
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10 pages, 559 KB  
Review
Paradigm Shifts in Diabetes Management: Key Highlights from the 2026 American Diabetes Association Standards of Care in Diabetes
by Dipti Tiwari, Wann Jia Loh and Tar Choon Aw
LabMed 2026, 3(2), 10; https://doi.org/10.3390/labmed3020010 - 27 Mar 2026
Abstract
The ADA 2026 Standards of Care in Diabetes introduces pivotal updates that refine diagnostic and therapeutic workflows. Expanding upon the 2025 guidelines, the 2026 edition broadens continuous-glucose-monitoring (CGM) eligibility to include all individuals on insulin or non-insulin therapies where CGM aids management. Significant [...] Read more.
The ADA 2026 Standards of Care in Diabetes introduces pivotal updates that refine diagnostic and therapeutic workflows. Expanding upon the 2025 guidelines, the 2026 edition broadens continuous-glucose-monitoring (CGM) eligibility to include all individuals on insulin or non-insulin therapies where CGM aids management. Significant new guidance addresses hyperglycemia management in oncology, identifying metformin as the preferred first-line intervention for drug-induced glycemic excursions. Additionally, type 1-diabetes (T1D) risk stratification is refined; a confirmed single IA-2 autoantibody now warrants monitoring levels similar to the Stage 2 disease. Furthermore, prerequisites for automated-insulin-delivery (AID) initiation have been removed to streamline technology access. For laboratory professionals, these revisions emphasize the critical role of advanced glycemic metrics and precise autoantibody profiling in complex clinical contexts. Full article
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