Diagnostics

12 pages, 543 KB

Open AccessEditor’s ChoiceReview

Molecular Pathology, Artificial Intelligence, and New Technologies in Hematologic Diagnostics: Translational Opportunities and Practical Considerations

by Fnu Alnoor, Shuvam Mukherjee, Madhu P. Menon, David Ng, Peng Li and Robert S. Ohgami

Diagnostics 2026, 16(6), 913; https://doi.org/10.3390/diagnostics16060913 - 19 Mar 2026

Viewed by 1077

Abstract

Background and Objectives: Diagnostics for hematologic diseases rely on integrated assessment of clinical manifestation, morphology, flow cytometry, and molecular testing. Current classification systems, including the WHO HAEM5 and the International Consensus Classification, highlight the central role of genomics in defining disease entities and [...] Read more.

Background and Objectives: Diagnostics for hematologic diseases rely on integrated assessment of clinical manifestation, morphology, flow cytometry, and molecular testing. Current classification systems, including the WHO HAEM5 and the International Consensus Classification, highlight the central role of genomics in defining disease entities and risk. Simultaneously, laboratories face growing case complexity and staffing challenges. Automation, collaborative robots (cobots), digital morphology platforms, and artificial intelligence (AI) have begun to address these issues. Here we examine the application of these technologies in hematopathology and molecular diagnostics and consider their translational potential to improve diagnostic accuracy and, ultimately, patient care. Methods: A review of peer-reviewed literature and technical reports published through December 2025 was performed, focusing on digital morphology platforms, AI for peripheral blood and marrow interpretation, AI-enabled flow cytometry, automated and robotic deployments in clinical laboratories, and machine learning applications in molecular hematopathology. Results: Digital morphology analyzers show strong concordance with manual microscopy and now serve as efficient platforms for AI-assisted differentials, cell classification, and fibrosis quantification. Deep learning applied to multiparameter flow cytometry achieves performance comparable to expert review in distinguishing mature B-cell neoplasms and acute leukemias. Automated solutions, cobot systems and robotic-arm-based slide-scanning clusters have demonstrated substantial gains in throughput and pre-analytic consistency. AI models in molecular hematopathology increasingly assist with variant interpretation, genetic risk stratification, and linking morphologic and genomic findings. Conclusions: AI is beginning to change how hematopathology and molecular diagnostics are practiced. Successful translation will depend on disease-specific validation, the development of multi-modal models aligned with ICC and WHO frameworks, and laboratory governance that maintains expert oversight. Full article

(This article belongs to the Special Issue Innovative Research and Operational Advances in the Diagnosis of Hematologic Diseases)

► Show Figures

Figure 1

25 pages, 9925 KB

Open AccessEditor’s ChoiceReview

Comprehensive Imaging Evaluation and Staging of Crohn’s Disease: When and Why to Use Intestinal Ultrasound, MRE, or CTE: Current Guidelines and Future Directions

by Francesca Maccioni, Ludovica Busato, Lorenza Bottino, Alessandro Longhi, Alessandra Valenti, Maddalena Zippi and Carlo Catalano

Diagnostics 2026, 16(6), 882; https://doi.org/10.3390/diagnostics16060882 - 16 Mar 2026

Viewed by 1135

Abstract

Crohn’s disease (CD) is a complex inflammatory bowel disease, defined by chronic transmural inflammation and marked heterogeneity in both anatomical distribution and disease behavior, with potential involvement of any segment of the gastrointestinal tract and multiple phenotypes. Advanced cross-sectional imaging nowadays plays a [...] Read more.

Crohn’s disease (CD) is a complex inflammatory bowel disease, defined by chronic transmural inflammation and marked heterogeneity in both anatomical distribution and disease behavior, with potential involvement of any segment of the gastrointestinal tract and multiple phenotypes. Advanced cross-sectional imaging nowadays plays a central role in CD management, reliably assessing both luminal and extraluminal inflammatory manifestations, supporting initial diagnosis, phenotypic characterization, and longitudinal monitoring of disease activity, complications and treatment response. Over the last two decades, Intestinal Ultrasound (IUS), MR Enterography (MRE), and Computed Tomography Enterography (CTE) have become central components of the diagnostic pathway. MRE has emerged as the most comprehensive, radiation-free modality for evaluating intestinal extent, inflammatory activity, and complications in Crohn’s disease. Multiparametric MRE, combining T2-weighted imaging, contrast-enhanced sequences, diffusion-weighted imaging, and cine acquisitions, enables a real “Crohn’s disease staging”, namely a thorough evaluation of the transmural inflammation, of fibrotic and fistulizing lesions in the small and large bowel, as well as in the perianal region. IUS provides a dynamic, widely accessible, safe and repeatable imaging technique that is particularly well suited for tight-monitoring strategies, early assessment of therapeutic response, and routine follow-up, especially in experienced centers. Notably CTE, despite concerns related to cumulative ionizing radiation exposure, remains indispensable in acute clinical settings owing to its rapid acquisition, broad availability, and high diagnostic accuracy for detecting abscesses, perforation, and bowel obstruction. Combined, these three modalities offer a complementary and patient-tailored framework for optimal CD management. This review outlines the pathological complexity of Crohn’s disease, traces the evolution of imaging approaches, and provides a comparative overview highlighting the specific strengths and limitations of each modality. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

12 pages, 814 KB

Open AccessEditor’s ChoiceReview

Acute Gastrointestinal Bleeding: An Update and a Practical Diagnostic Approach

by Elio Antonucci, Ilaria Zanichelli and Alessandro Rimondi

Diagnostics 2026, 16(6), 860; https://doi.org/10.3390/diagnostics16060860 - 13 Mar 2026

Viewed by 1746

Abstract

Acute gastrointestinal bleeding (GIB) is one of the most common and dangerous condition in patients admitted in Emergency Departments. The incidence and the mortality of acute GIB remain significant, although some positive trends were observed in recent years. Initial evaluation of GIB needs [...] Read more.

Acute gastrointestinal bleeding (GIB) is one of the most common and dangerous condition in patients admitted in Emergency Departments. The incidence and the mortality of acute GIB remain significant, although some positive trends were observed in recent years. Initial evaluation of GIB needs an accurate assessment of the medical history and the clinical presentation. Physicians should pay attention about the presence of hemorrhagic shock that usually requires urgent diagnosis and treatment. Only a prompt diagnostic approach can identify the source of bleeding and improve the outcomes in acute GIB patients. Risk stratification and time of endoscopy are fundamental issues in the management of upper and lower GIB. Small bowel capsule enteroscopy (SBCE) and device-assisted enteroscopy (DAE) are the basic approaches to suspected small bowel bleeding. Machine Learning Prognostic Models have been proposed, such as alternative prognostic tools in GIB, but they are currently recommended only to identify low-risk outpatients. Full article

(This article belongs to the Special Issue Advances in Clinical and Interventional Gastroenterology)

► Show Figures

Figure 1

13 pages, 246 KB

Open AccessEditor’s ChoiceReview

Innovations in Robotic-Assisted Bronchoscopy: Current Trends and Future Prospects

by Joshua M. Boster, S. Michael Goertzen, Brian D. Tran and Robert F. Browning, Jr.

Diagnostics 2026, 16(6), 832; https://doi.org/10.3390/diagnostics16060832 - 11 Mar 2026

Viewed by 1282

Abstract

Robotic-assisted bronchoscopy (RAB) represents a significant technological advance, providing superior precision, enhanced visualization, and increased maneuverability relative to conventional bronchoscopic methods. This review provides an overview of current research evaluating RAB’s diagnostic performance and exploring future prospects. Recent literature demonstrates advantages in navigating [...] Read more.

Robotic-assisted bronchoscopy (RAB) represents a significant technological advance, providing superior precision, enhanced visualization, and increased maneuverability relative to conventional bronchoscopic methods. This review provides an overview of current research evaluating RAB’s diagnostic performance and exploring future prospects. Recent literature demonstrates advantages in navigating difficult-to-reach lung lesions with improved safety profiles compared to transthoracic approaches. Incorporating advanced imaging technologies has enhanced real-time decision-making during procedures, and artificial intelligence applications are emerging. RAB has been rapidly adopted at many high-volume centers based on favorable navigational success and safety data. As the field matures, ongoing prospective studies will further define its role in improving patient outcomes, cost-effectiveness, and optimal integration with lung cancer screening programs. RAB faces ongoing challenges including substantial capital costs, training requirements, and need for standardized protocols. Therapeutic applications show promise and are under active investigation. Full article

(This article belongs to the Special Issue Advances in Interventional Pulmonology)

18 pages, 294 KB

Open AccessEditor’s ChoiceArticle

Assessment of Thrombotic Risk in Patients with Tuberculosis and SARS-CoV-2 Coinfection: A Retrospective Study

by Sofia Teodora Muntean, Andreea-Raluca Cozac-Szoke, Diana Maria Chiorean, Adrian Horațiu Sabău, Iuliu Gabriel Cocuz, Raluca Niculescu, Claudia Raluca Mariean, Ovidiu Simion Cotoi and Anca Ileana Sin

Diagnostics 2026, 16(5), 724; https://doi.org/10.3390/diagnostics16050724 - 28 Feb 2026

Viewed by 436

Abstract

Background/Objectives: Tuberculosis and COVID-19 are two major infectious diseases with significant inflammatory and immunological impact on infected hosts and both conditions are independently associated with a prothrombotic state. However, evidence regarding their combined effect on in-hospital thrombotic risk remains limited. In this study, [...] Read more.

Background/Objectives: Tuberculosis and COVID-19 are two major infectious diseases with significant inflammatory and immunological impact on infected hosts and both conditions are independently associated with a prothrombotic state. However, evidence regarding their combined effect on in-hospital thrombotic risk remains limited. In this study, we aimed to explore whether patients with tuberculosis and COVID-19 coinfection are at a higher risk of developing thrombotic events during hospitalization than patients diagnosed with tuberculosis alone. Materials and Methods: We performed a retrospective, single-center cohort study, including adults hospitalized at the Pulmonology Clinic, Adult Tuberculosis ward of Mures County Clinical Hospital, between 2021 and 2023. Two groups were analyzed: patients with pulmonary tuberculosis who developed COVID-19 during hospitalization (n = 40) and patients with pulmonary tuberculosis without documented SARS-CoV-2 infection (n = 40). Demographic, clinical, laboratory, and imaging data were extracted from medical records. Padua and IMPROVE-DD scores were calculated retrospectively, a rapid mini-score was evaluated exploratorily. Comparisons between groups were performed using appropriate statistical tests and unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Given the limited number of events, an age-adjusted Firth penalized logistic regression model was used for multivariable analysis. Results: Thrombotic events occurred more frequently in the tuberculosis and COVID-19 co-infection group (22.5% vs. 10%), although statistical significance was not reached (p = 0.22; OR = 2.61). Patients with coinfection had significantly higher proportions of elevated Padua scores (55% vs. 20%, p = 0.002; OR = 4.88), while IMPROVE-DD showed values near the conventional threshold for statistical significance (37.5% vs. 17.5%, p = 0.07). D-dimer values did not reach statistical significance (p = 0.07) and platelet counts were significantly higher in patients with tuberculosis only (p = 0.001). Mortality did not differ significantly between groups (15% vs. 10%, p = 0.73). In age-adjusted multivariable analysis, tuberculosis and COVID-19 coinfection remained associated with higher odds of thrombotic events, with wide confidence intervals. Conclusions: Patients with concomitant tuberculosis and COVID-19 showed a higher thrombotic risk profile (Padua score) and numerically higher rates of in-hospital thrombotic events, without reaching statistical significance. Findings should be interpreted as exploratory and hypothesis-generating. Larger prospective studies with systematic imaging and multivariable adjustment are needed. Full article

(This article belongs to the Special Issue Recent Advances in Epidemiological Diagnostics: Detecting and Controlling Infectious Diseases)

17 pages, 1772 KB

Open AccessEditor’s ChoiceReview

Lipid Metabolism and Ferroptosis Resistance in Dormant Breast Cancer Cells: Emerging Therapeutic Vulnerabilities

by Giulia Capella, Fulvio Borella, Eleonora Battista, Niccolò Gallio, Mathilde Hotot, Luca Bertero, Paola Cassoni and Isabella Castellano

Diagnostics 2026, 16(5), 667; https://doi.org/10.3390/diagnostics16050667 - 25 Feb 2026

Viewed by 805

Abstract

Late metastatic relapses still represent a major clinical challenge in breast cancer, particularly in hormone receptor-positive (HR+) disease, with dormant disseminated tumor cells (DTCs) playing a critical role in driving late metastatic relapses. In fact, these cells can persist in a quiescent, non-proliferative [...] Read more.

Late metastatic relapses still represent a major clinical challenge in breast cancer, particularly in hormone receptor-positive (HR+) disease, with dormant disseminated tumor cells (DTCs) playing a critical role in driving late metastatic relapses. In fact, these cells can persist in a quiescent, non-proliferative state in metabolically hostile microenvironments such as the bone marrow, where they can resist conventional therapies, driving metastatic relapses even years after primary tumor removal. Recent advances highlight the crucial role of lipid metabolism in protecting dormant DTCs from ferroptosis—a form of regulated cell death characterized by iron-dependent lipid peroxidation. Dormant DTCs can avoid lipid peroxidation by incorporating monounsaturated fatty acids (MUFAs) into membrane phospholipids through ACSL3 and SCD1 activity, while accumulating lipid droplets (LDs) that sequester oxidizable polyunsaturated fatty acids (PUFAs), thus limiting the substrates available for ferroptosis. In parallel, antioxidant systems such as the GPX4–glutathione axis further prevent lethal lipid-derived reactive oxidative species (ROS) accumulation. This review highlights the central role of lipid metabolism, redox regulation and ferroptosis resistance in dormant DTCs; it also explores emerging therapeutic opportunities to overcome dormancy-associated resistance and reduce late relapse risk in breast cancer. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Breast Cancer)

► Show Figures

Figure 1

23 pages, 2991 KB

Open AccessEditor’s ChoiceReview

Diagnostic Imaging of Extrapulmonary Tuberculosis Across Organ Systems

by Madeleine T. Dang, Kara Lukas, Daniel H. Choi, Timothy J. Chu and Vishwanath Venketaraman

Diagnostics 2026, 16(4), 586; https://doi.org/10.3390/diagnostics16040586 - 15 Feb 2026

Viewed by 1698

Abstract

Extrapulmonary tuberculosis (EPTB) is an infectious disease characterized by the invasion of Mycobacterium tuberculosis beyond the lungs. Diagnosis is frequently delayed due to nonspecific clinical presentations that vary by organ system, making diagnostic imaging essential for disease detection, characterization, and treatment monitoring. The [...] Read more.

Extrapulmonary tuberculosis (EPTB) is an infectious disease characterized by the invasion of Mycobacterium tuberculosis beyond the lungs. Diagnosis is frequently delayed due to nonspecific clinical presentations that vary by organ system, making diagnostic imaging essential for disease detection, characterization, and treatment monitoring. The objective of this review is to examine and summarize imaging-based approaches for the diagnostic evaluation of EPTB across multiple body systems, including the central nervous system, spine, cardiovascular system, lymphatic system, abdominal and hepatic organs, genitourinary tract, cutaneous and soft tissue, and other rare sites. While computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound are widely used in the evaluation of EPTB, their ability to provide a definitive diagnosis is often limited by nonspecific radiologic findings. Emerging techniques, including perfusion-weighted MRI, contrast-enhanced ultrasound, and machine learning, have been discussed, as they improve lesion characterization and EPTB differentiation. By organizing imaging findings according to affected organ systems, this review highlights both shared diagnostic challenges and site-specific patterns that can inform clinical suspicion. Together, these developments underscore the value of a multimodal, organ-specific imaging approach integrated with the clinical context to improve the recognition and management of EPTB. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

19 pages, 1810 KB

Open AccessEditor’s ChoiceReview

CBCT Assessment for Dental Implant Surgery at the Maxilla: A Clinical Update

by Wai Yu Chelsea Chung, Feng Wang and Yiu Yan Leung

Diagnostics 2026, 16(3), 479; https://doi.org/10.3390/diagnostics16030479 - 4 Feb 2026

Cited by 1 | Viewed by 1633

Abstract

In contemporary practice, dental implants are widely recognized as a reliable and effective solution for rehabilitating edentulous patients. Nevertheless, implant placement in the atrophied maxilla presents considerable challenges, with treatment planning influenced by various factors such as patient demographics, anatomical constraints, and economic [...] Read more.

In contemporary practice, dental implants are widely recognized as a reliable and effective solution for rehabilitating edentulous patients. Nevertheless, implant placement in the atrophied maxilla presents considerable challenges, with treatment planning influenced by various factors such as patient demographics, anatomical constraints, and economic considerations. Advances in imaging technology have positioned cone-beam computed tomography (CBCT) as the preferred modality for enhancing implant placement accuracy. By producing high-resolution three-dimensional radiographic images, CBCT facilitates precise assessment of maxillary anatomy at the proposed implant site—including bone height, width, length, and angulation—thereby optimizing surgical planning and improving the predictability and success rates of implant integration. Moreover, the timing of implant placement must account for the necessity of maxillary augmentation to ensure implant stability and reduce the risk of postoperative complications. This review discusses the clinical utility of CBCT as a diagnostic tool for preoperative assessment, focusing on the identification of critical anatomical landmarks and the determination of indications for bone augmentation, thereby highlighting its crucial role in enabling accurate treatment planning, minimizing surgical risks, and promoting the long-term survival of dental implants. Full article

(This article belongs to the Special Issue Application of Cone Beam Computed Tomography for Maxillofacial Diseases, Third Edition)

► Show Figures

Figure 1

13 pages, 4153 KB

Open AccessEditor’s ChoiceArticle

JAK3 Staining and CD68+ Macrophage Counts Are Increased in Patients with IgA Nephropathy

by Mateus Justi Luvizotto, Precil Diego Miranda de Menezes Neves, Cristiane Bitencourt Dias, Lecticia Barbosa Jorge, Luis Yu, Luísa Menezes-Silva, Magaiver Andrade-Silva, Renato C. Monteiro, Niels Olsen Saraiva Câmara and Viktoria Woronik

Diagnostics 2026, 16(3), 437; https://doi.org/10.3390/diagnostics16030437 - 1 Feb 2026

Viewed by 553

Abstract

Background/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to [...] Read more.

Background/Objectives: IgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide; it is characterized by a complex pathophysiology involving several inflammatory pathways. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may be critical in this process. This study aimed to investigate the role of this pathway in IgAN and examine related tissue inflammatory markers. Methods: We analyzed 63 biopsy-confirmed patients with IgAN and performed immunohistochemical analysis on renal samples. A panel of antibodies targeting the JAK/STAT pathway, including JAK2, JAK3, p-STAT, STAT3, and MAPK/ERK, was used for this analysis. Six kidney tumor border samples were used as controls. Additionally, CD68 staining was used to evaluate tissue inflammation in the kidney biopsies. Results: Patients with IgAN showed a significantly higher cellular density of JAK3 staining at the glomerular level compared to controls, indicating JAK3 activation (p < 0.0002). Nevertheless, the correlation between JAK3 positivity in glomeruli and clinical parameters such as the initial and final estimated glomerular filtration rate (eGFR) and proteinuria was not statistically significant. Identical results were obtained with CD68+ macrophage counts in the glomerular compartment, which did not show any correlation with clinical parameters, while CD68+ tubulointerstitial staining demonstrated a significant correlation with both initial (p = 0.002) and final eGFRs (p = 0.0014), proteinuria (p = 0.010), and interstitial fibrosis (p < 0.001), as well as with renal disease progression (p = 0.005). Conclusions: Activation of the JAK/STAT pathway was observed in patients with IgAN relative to controls, notwithstanding the inability to assess the full pathway due to technical limitations. Macrophage CD68 staining in the tubulointerstitial area increased and was associated with clinical and laboratory parameters such as eGFR and proteinuria. Additionally, MEST-C histological parameters, such as segmental glomerulosclerosis (S0/S1), tubular atrophy/interstitial fibrosis (T0/T1/T2), and crescents (C0/C1/C2), were associated with a higher number of CD68+ cells. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)

► Show Figures

Figure 1

12 pages, 833 KB

Open AccessEditor’s ChoiceArticle

Safety of a Tailored Gadolinium-Based Contrast Agent Protocol Considering Excretion Pathways in Patients with Renal Impairment

by Jeong Woo Kim, Chang Hee Lee, Gang-Jee Ko and Sang-Il Suh

Diagnostics 2026, 16(3), 451; https://doi.org/10.3390/diagnostics16030451 - 1 Feb 2026

Viewed by 868

Abstract

Background/Objectives: Considering the excretion pathways and administered gadolinium dose, our institution has developed a tailored gadolinium-based contrast agents (GBCAs) administration protocol for patients with renal impairment to facilitate more rapid elimination and minimal retention of gadolinium. This study aims to evaluate the 8-year [...] Read more.

Background/Objectives: Considering the excretion pathways and administered gadolinium dose, our institution has developed a tailored gadolinium-based contrast agents (GBCAs) administration protocol for patients with renal impairment to facilitate more rapid elimination and minimal retention of gadolinium. This study aims to evaluate the 8-year clinical outcomes and safety of this institutional protocol. Methods: This single-center retrospective study included patients with renal impairment who underwent GBCA-enhanced MRI between January 2015 and December 2022. The protocol recommended specific GBCAs and adjusted doses based on chronic kidney disease (CKD) stage and serum bilirubin levels: gadoxetate disodium was used for normal serum bilirubin level due to its dual excretion pathway, while macrocyclic agents were used for those with elevated serum bilirubin levels. During the follow-up period, occurrence of nephrogenic systemic fibrosis (NSF) and evidence of gadolinium deposition in brain tissues were evaluated. Results: A total of 288 patients (age, 64.6 ± 11.7 years; male, 64.9%) underwent 716 GBCA-enhanced MRI examinations in accordance with the institutional protocol. The cohort included 62 patients with CKD stage 4 and 131 patients with CKD stage 5 or undergoing hemodialysis. In patients with CKD stage 4 and 5 and those undergoing hemodialysis, 597 examinations were performed using gadoxetate disodium, and 119 used macrocyclic agents. No cases of NSF or gadolinium deposition in brain tissues were identified over mean follow-up intervals of 27.5 and 27.8 months, respectively. Conclusions: The tailored GBCA administration protocol, considering the excretion pathways and administered gadolinium dose, appears to be safe with respect to NSF for patients with renal impairment, and no evidence of brain gadolinium deposition was observed in the evaluated subset of patients. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

13 pages, 774 KB

Open AccessEditor’s ChoiceArticle

Dynamic Thyroglobulin Ratio as a Biomarker to Identify Papillary Thyroid Cancer Patients Who Would Benefit from a Low-Iodine Diet

by Su Woong Yoo, Yong Min Na, Young Jae Ryu, Hee Kyung Kim, Hyun-Jung Choi and Seong-Young Kwon

Diagnostics 2026, 16(3), 456; https://doi.org/10.3390/diagnostics16030456 - 1 Feb 2026

Viewed by 578

Abstract

Objectives: This study aimed to assess whether low-iodine diet (LID) adherence is associated with therapeutic response in papillary thyroid carcinoma (PTC), specifically in relation to post-therapeutic thyroglobulin (Tg) release as a surrogate marker for the acute radiation-induced response following radioactive iodine (RAI) [...] Read more.

Objectives: This study aimed to assess whether low-iodine diet (LID) adherence is associated with therapeutic response in papillary thyroid carcinoma (PTC), specifically in relation to post-therapeutic thyroglobulin (Tg) release as a surrogate marker for the acute radiation-induced response following radioactive iodine (RAI) therapy. Methods: This retrospective study included 895 patients with PTC treated with RAI. LID adherence was assessed using the urine iodine-to-creatinine (I/Cr) ratio, with <66.2 μg/g Cr defined as good adherence. The Tg ratio (ratioTg), calculated by dividing post-RAI Tg (measured 7 days after RAI) by pre-RAI Tg, was used to reflect the magnitude of the radiation-induced Tg release. Patients were stratified by ratioTg (≤1 vs. >1), and associations between LID adherence and therapeutic response were analyzed within each group. Results: Well-adherent patients exhibited significantly higher ratioTg compared to poorly adherent patients (15.7 ± 2.2 vs. 8.9 ± 1.3, p = 0.007). Among patients with ratioTg > 1 (n = 630), LID adherence was independently associated with improved therapeutic response (OR, 2.004; 95% CI, 1.270–3.162; p = 0.003). No such association was observed in patients with ratioTg ≤ 1 (n = 265; p = 0.546). Conclusions: The clinical benefit of LID appears to depend on the presence of a certain magnitude of radiation-induced Tg release. RatioTg may serve as a useful marker for identifying patients likely to benefit from LID. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)

► Show Figures

Figure 1

14 pages, 3366 KB

Open AccessEditor’s ChoiceArticle

Prognostic Value of CT-Derived Indicators of Right-Heart Strain and Thrombus Burden for In-Hospital Adverse Events in Acute Pulmonary Embolism

by Corina Cinezan, Camelia Bianca Rus, Alina Cristiana Venter and Angela Cozma

Diagnostics 2026, 16(2), 290; https://doi.org/10.3390/diagnostics16020290 - 16 Jan 2026

Viewed by 2735

Abstract

Background: Accurate risk stratification in acute pulmonary embolism (PE) is critical for guiding management. This study assessed the prognostic value of computed tomography (CT) indicators of right-heart strain and thrombus burden for predicting in-hospital adverse events. Methods: In this retrospective cohort [...] Read more.

Background: Accurate risk stratification in acute pulmonary embolism (PE) is critical for guiding management. This study assessed the prognostic value of computed tomography (CT) indicators of right-heart strain and thrombus burden for predicting in-hospital adverse events. Methods: In this retrospective cohort of 300 patients with CT-confirmed acute PE, the right-to-left ventricular (RV/LV) diameter ratio, Pulmonary Artery Obstruction Index (PAOI), and inferior vena cava (IVC) contrast reflux were measured. The primary endpoint was in-hospital adverse events, including hemodynamic collapse, vasopressor or ventilatory support, rescue reperfusion therapy, or death. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: Adverse events occurred in 106 patients (35.3%). Compared with stable patients, those with events had higher RV/LV ratios (1.45 vs. 1.03), higher PAOI (38.8 vs. 24.3), and more frequent IVC reflux (74% vs. 7%) (all p < 0.001). Independent predictors were RV/LV ratio (aOR 3.22 per 0.1), PAOI (aOR 5.53 per 10 points), and IVC reflux (aOR 428.5; all p < 0.001). The model showed excellent discrimination (AUC = 0.96). Conclusions: CT-derived indices of right-heart strain and thrombus burden are strong, independent predictors of in-hospital adverse events in acute PE and should be integrated into routine CT-based risk assessment. Full article

(This article belongs to the Special Issue Diagnosis of Cardio-Thoracic Diseases)

► Show Figures

Figure 1

21 pages, 78949 KB

Open AccessEditor’s ChoiceArticle

FGF2 as a Potential Tumor Suppressor in Lung Adenocarcinoma

by Shih-Sen Lin, Hsin-Ying Lu, Tsung-Ming Chang, Ying-Sui Sun and Ju-Fang Liu

Diagnostics 2026, 16(2), 250; https://doi.org/10.3390/diagnostics16020250 - 13 Jan 2026

Viewed by 780

Abstract

Background/Objectives: Lung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), is frequently diagnosed at advanced stages with distant metastasis, underscoring the need for effective prognostic biomarkers. Fibroblast growth factor 2 (FGF2), a multifunctional regulator, has shown to play contradictory [...] Read more.

Background/Objectives: Lung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), is frequently diagnosed at advanced stages with distant metastasis, underscoring the need for effective prognostic biomarkers. Fibroblast growth factor 2 (FGF2), a multifunctional regulator, has shown to play contradictory roles in cancer progression. Methods: We analyzed three independent Gene Expression Omnibus (GEO) datasets (GSE19804, GSE18842, and GSE19188) to identify consistently dysregulated genes in LUAD. Functional enrichment (GO, KEGG, and cancer hallmark analysis), protein–protein interaction (PPI) network construction, and hub gene prioritization were performed using public bioinformatic tools. Survival analyses were conducted via the Kaplan–Meier Plotter. The expression of FGF2 was validated across multiple platforms, including TCGA, CPTAC, TNMplot, LCE, and the Human Protein Atlas. Functional assays (Transwell migration and wound healing) demonstrated that exogenous FGF2 significantly suppressed LUAD cell motility in vitro. Results: A total of 949 differentially expressed genes (DEGs) were commonly identified across datasets, with enrichment in cell adhesion and metastasis-related pathways. Among the 11 hub genes identified, FGF2 was consistently downregulated in LUAD tissues across all datasets and stages. Higher FGF2 expression was associated with longer overall and progression-free survival. In vitro, FGF2 treatment significantly suppressed the migration and wound healing abilities of LUAD cell lines. Conclusions: FGF2 is downregulated in LUAD and inversely associated with metastatic progression and poor prognosis. The observed reduction in cancer cell motility upon FGF2 treatment in vitro, together with its expression pattern, supports a potential tumor-suppressive role and suggests that FGF2 may serve as a candidate non-invasive biomarker for monitoring LUAD metastasis. Full article

(This article belongs to the Special Issue Advances in Molecular Pathology and Imaging for Precision Diagnosis and Treatment of Tumors)

► Show Figures

Figure 1

25 pages, 12897 KB

Open AccessEditor’s ChoiceReview

Echocardiographic Assessment of Left Ventricular Diastolic Function in Adults Between Old and New: Progress and Challenges

by Luca Dell’Angela and Gian Luigi Nicolosi

Diagnostics 2026, 16(2), 235; https://doi.org/10.3390/diagnostics16020235 - 11 Jan 2026

Viewed by 1894

Abstract

Echocardiographic left ventricular (LV) diastolic function assessment represents one of the mainstays for routine, comprehensive transthoracic echocardiography in adults. Estimation of LV filling pressures is an integral part of LV diastolic function evaluation. Additionally, LV diastolic function assessment is crucial for the study [...] Read more.

Echocardiographic left ventricular (LV) diastolic function assessment represents one of the mainstays for routine, comprehensive transthoracic echocardiography in adults. Estimation of LV filling pressures is an integral part of LV diastolic function evaluation. Additionally, LV diastolic function assessment is crucial for the study of subjects with potential heart failure with preserved LV ejection fraction. Beyond the “old” LV diastolic function parameters, to date, mostly strain-based (and generally artificial intelligence-assisted) additional “new” echocardiographic techniques have emerged to optimize the study of LV diastole. The purpose of the present narrative critical review is to report and discuss the optimal echocardiographic assessment of LV diastolic function in light of the recent literature, with the aim of trying to outline the gaps in the current evidence in view of future developments. To date, multiparametric diastolic evaluation and grading seem advisable, using as many “old and new” measurements as possible—associated with their adequate selection related to the patients’ comorbidities—aiming to cumulatively increase the advantages of diastolic parameters and possibly minimize their limitations. Taking into account the considerable number of echocardiographic measurements to perform and describe, at present, the timing of optimal echocardiography performance and reporting should be adequately adapted to the current technical needs and real-life routine clinical practice. Importantly, contextual clinical and (if needed) multimodality assessment should be included in the diagnostic workflow, in order to enable a more individualized approach. Full article

(This article belongs to the Special Issue Recent Advances in Echocardiography, 2nd Edition)

► Show Figures

Figure 1

24 pages, 766 KB

Open AccessEditor’s ChoiceSystematic Review

Artificial Intelligence-Based Automated Analysis for Pleural Effusion Detection on Thoracic Ultrasound: A Systematic Review

by Guido Marchi, Luciano Gabbrielli, Marco Gherardi, Massimiliano Serradori, Francesco Baglivo, Salvatore Claudio Fanni, Jacopo Cefalo, Carmine Salerni, Giacomo Guglielmi, Francesco Pistelli, Laura Carrozzi and Michele Mondoni

Diagnostics 2026, 16(1), 147; https://doi.org/10.3390/diagnostics16010147 - 2 Jan 2026

Cited by 2 | Viewed by 1498

Abstract

Background: Pleural effusion (PE) is a common condition where accurate detection is essential for management. Thoracic ultrasound (TUS) is the first-line modality owing to safety, portability, and high sensitivity, but accuracy is operator-dependent. Artificial intelligence (AI)-based automated analysis has been explored as [...] Read more.

Background: Pleural effusion (PE) is a common condition where accurate detection is essential for management. Thoracic ultrasound (TUS) is the first-line modality owing to safety, portability, and high sensitivity, but accuracy is operator-dependent. Artificial intelligence (AI)-based automated analysis has been explored as an adjunct, with early evidence suggesting potential to reduce variability and standardise interpretation. This review evaluates the diagnostic accuracy of AI-assisted TUS for PE detection. Methods: This review was registered with PROSPERO (CRD420251128416) and followed PRISMA guidelines. MEDLINE, Scopus, Google Scholar, IEEE Xplore, Cochrane CENTRAL, and ClinicalTrials.gov were searched through 20 August 2025 for studies assessing AI-based TUS analysis for PE. Eligible studies required recognised reference standards (expert interpretation or chest CT). Risk of bias was assessed with QUADAS-2, and certainty with GRADE. Owing to heterogeneity, structured narrative synthesis was performed instead of meta-analysis. Results: Five studies (7565 patients) published between 2021–2025 were included. All used convolutional neural networks with varied architectures (ResNet, EfficientNet, U-net). Sensitivity ranged 70.6–100%, specificity 67–100%, and AUC 0.77–0.99. Performance was reduced for small, trace, or complex effusions and in critically ill patients. External validation showed attenuation compared with internal testing. All studies had high risk of bias in patient selection and index test conduct, reflecting retrospective designs and inadequate dataset separation. Conclusions: AI-assisted TUS shows promising diagnostic performance for PE detection in curated datasets; however, evidence is inconsistent and limited by key methodological weaknesses. Overall certainty is low-to-moderate, constrained by retrospective designs, limited dataset separation, and scarce external validation. Current evidence is insufficient to support routine clinical use. Robust prospective multicentre studies with rigorous independent validation and evaluation of clinically meaningful outcomes are essential before clinical implementation can be considered. Full article

(This article belongs to the Special Issue Diagnostic Imaging of Pulmonary Diseases)

► Show Figures

Figure 1

23 pages, 6554 KB

Open AccessEditor’s ChoiceArticle

BacT-Seq, a Nanopore-Based Whole-Genome Sequencing Workflow Prototype for Rapid and Accurate Pathogen Identification and Resistance Prediction from Positive Blood Cultures: A Feasibility Study

by Meriem El Azami, Véronique Lanet, Corinne Beaulieu, Aurélien Griffon, Stéphane Schicklin, Pierre Mahé, Marion Darnaud, Marion Helsmoortel, Erwin Sentausa, Adrien Saliou, Mallory Poncelet, Raphaël Fleury, Marine Ibranosyan, François Vandenesch and Emmanuelle Santiago-Allexant

Diagnostics 2026, 16(1), 133; https://doi.org/10.3390/diagnostics16010133 - 1 Jan 2026

Cited by 2 | Viewed by 1605

Abstract

Background/Objectives: Rapid and accurate pathogen identification and antimicrobial susceptibility testing (AST) are critical for the proper management of patients with bloodstream infection (BSI). Real-time whole-genome sequencing (WGS) represents an attractive opportunity for exhaustive pathogen identification and antimicrobial susceptibility prediction (ASP). This feasibility [...] Read more.

Background/Objectives: Rapid and accurate pathogen identification and antimicrobial susceptibility testing (AST) are critical for the proper management of patients with bloodstream infection (BSI). Real-time whole-genome sequencing (WGS) represents an attractive opportunity for exhaustive pathogen identification and antimicrobial susceptibility prediction (ASP). This feasibility study introduces BacT-Seq, a WGS-based prototype assay for the rapid and accurate identification of pathogens and the prediction of antimicrobial susceptibility from positive blood cultures using Oxford Nanopore Technologies (ONT) sequencing. Methods: A total of 200 positive blood culture samples from patients with a confirmed BSI were included in this study. DNA isolation from blood cultures was optimized prior to GridION (ONT) sequencing. Pathogen identification and several ASP methods were compared to conventional identification and phenotypic AST methods. Results: Most of the mono-microbial (89%) and poly-microbial (88%) samples were identified by BacT-Seq in less than 10 min of sequencing. While identification of poly-microbial samples remains challenging, identification of mono-microbial samples by sequencing was non-inferior to that of the conventional approach, even revealing an added value in terms of exhaustivity and/or taxonomic resolution. Machine-learning-based ASP models yielded 80% predictions in 2.5 h of sequencing. Their ability to predict resistance phenotypes varied with the microbial species evaluated, from 55/57 (96.5%) for Escherichia coli to 24/48 (50.0%) for Pseudomonas aeruginosa. Conclusions: This study demonstrates the feasibility of implementation of the BacT-Seq platform for the fast and accurate identification of pathogens from positive blood cultures. BacT-Seq performance of resistance predictions by bioinformatics tools is promising but requires further optimization and validation before clinical implementation. Full article

(This article belongs to the Special Issue New Diagnostic and Testing Strategies for Infectious Diseases)

► Show Figures

Figure 1

13 pages, 253 KB

Open AccessEditor’s ChoiceStudy Protocol

Novel Biomarkers for Prognostic Assessment of Patients with Acute Exacerbation of COPD in the Emergency Department—Tools to Enhance the Quality of Care in Critical Patient Management

by Raluca Mihaela Tat, Sonia Luka, Eugenia Maria Lupan-Mureșan, George Teo Voicescu, Luca David, Adela Golea and Ștefan Cristian Vesa

Diagnostics 2026, 16(1), 122; https://doi.org/10.3390/diagnostics16010122 - 1 Jan 2026

Viewed by 1010

Abstract

Background/Objectives: Chronic obstructive pulmonary disease (COPD) remains a major global health problem, affecting over 300 million people worldwide. Its high morbidity and mortality rates impose substantial psychosocial and financial burdens on patients and healthcare systems. In the emergency setting, managing acute exacerbations [...] Read more.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) remains a major global health problem, affecting over 300 million people worldwide. Its high morbidity and mortality rates impose substantial psychosocial and financial burdens on patients and healthcare systems. In the emergency setting, managing acute exacerbations of COPD (AECOPD) poses a major clinical challenge, as these patients often present with multi-organ dysfunction secondary to hypoxia and hypercapnia. Identifying reliable prognostic biomarkers could improve early risk stratification, guide therapeutic decisions, and enhance patient outcomes. Methods: This multicenter, prospective, observational study aims to evaluate the prognostic significance of several novel biomarkers—resistin, club cell secretory protein 16 (CC16), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), S100β protein—alongside conventional markers such as N-terminal-pro–B-type-Natriuretic-Peptide (NT-proBNP), D-dimer, high-sensitivity troponin I (hs-cTnI), C-reactive protein (CRP), and procalcitonin in patients with AECOPD admitted to the Emergency Department (ED). Blood samples will be collected at admission. The novel biomarkers (resistin, CC16, IL-6, TNF-α, S100β) will be measured using standardized ELISA kits, while conventional biomarkers (NT-proBNP, troponin I, CRP, procalcitonin) will be analyzed using routine automated clinical laboratory methods. Correlations between biomarker levels, clinical and imaging data, severity scores (GCS, SOFA, CFS, Ottawa COPD Risk Scale, DECAF, BAP-65), and short-term outcomes (hospital discharge status and 28-day survival) will be assessed. The study has received approval from the Ethics Committee of the “Iuliu-Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, and all participating hospitals. Written informed consent will be obtained from all participants or their legal representatives. Results: This study protocol does not report results, as data collection and analysis are ongoing. Conclusions /Expected Impact: By identifying novel biomarkers with prognostic and pathophysiological relevance, this research aims to inform the development of early risk stratification tools and support future evidence-based approaches to the management of critically ill COPD patients in the ED. Full article

(This article belongs to the Special Issue Recent Advances in Clinical Biochemical Testing)

21 pages, 1648 KB

Open AccessEditor’s ChoiceArticle

Discovery of SOX5 as a New Causative Gene for Atrial Fibrillation

by Dao-Liang Zhang, Xing-Biao Qiu, Ning Li, Yuan-Yuan Ding, Chen-Xi Yang, Zun-Ping Ke, Ying-Jia Xu and Yi-Qing Yang

Diagnostics 2026, 16(1), 59; https://doi.org/10.3390/diagnostics16010059 - 24 Dec 2025

Cited by 1 | Viewed by 957

Abstract

Background/Objectives: Atrial fibrillation (AF), characteristic of chaotic atrial electrical activity along with ineffective atrial systole, remains the most frequent sustained cardiac dysrhythmia, with an overall lifetime risk for AF being approximately 15% to 40% in the global population. AF is associated with substantially [...] Read more.

Background/Objectives: Atrial fibrillation (AF), characteristic of chaotic atrial electrical activity along with ineffective atrial systole, remains the most frequent sustained cardiac dysrhythmia, with an overall lifetime risk for AF being approximately 15% to 40% in the global population. AF is associated with substantially enhanced risks for multiple adverse clinical outcomes, including thromboembolic cerebral stroke, dementia, chronic kidney disease, myocardial infarction, cardiac failure, and even premature cardiac demise. Although remarkable advances have been achieved toward unravelling the complex hereditary etiopathogenesis underpinning AF, it has become increasingly clear that inherited determinants predisposing to AF in a vast majority of individuals are still uncertain. Methods: A Chinese pedigree with idiopathic AF and another group of 236 cases suffering idiopathic AF along with 312 unrelated healthy volunteers were prospectively recruited. Exome-wide sequencing and Sanger sequencing assays were implemented in research participants. The functional effects of the discovered variations in the SOX5 gene were explored through dual-luciferase reporter analysis. Results: Two novel SOX5 mutants, NM_006940.6: c.355C>T; p.(Gln119*) and NM_006940.6: c.640G>T; p.(Glu214*), were identified in the AF pedigree and one of the 236 unrelated patients affected with AF, respectively. These two heterozygous truncating SOX5 variations were absent from the 624 control chromosomes. Quantitative luciferase reporter assays unraveled that both Gln119*- and Glu214*-mutant SOX5 lost the ability to transactivate GJA1. Additionally, the two variations abolished the synergistic transactivation of SCN5A by SOX5 and SHOX2. Conclusions: The current findings indicate SOX5 as a novel gene contributing to AF, which adds more insight to the molecular pathogenesis of AF, and provides a potential target for personalized precision medicine. Full article

(This article belongs to the Special Issue Genomics in Cardiac Diagnostics: Bridging Novel Insights to Clinical Practice)

► Show Figures

Figure 1

15 pages, 966 KB

Open AccessEditor’s ChoiceArticle

Long-Term Cardiovascular and Mortality Risk in Patients with Pre-Existing Arrhythmia Post-SARS-CoV-2 Infection

by Suhani Pahuja, Roham Hadidchi, Janhavi Tonge, Sonya Henry and Tim Q. Duong

Diagnostics 2026, 16(1), 38; https://doi.org/10.3390/diagnostics16010038 - 22 Dec 2025

Cited by 3 | Viewed by 1405

Abstract

Background/Objectives: Individuals with arrhythmia who survived COVID-19 could be susceptible to long-term cardiovascular complications and clinical outcomes. Methods: We performed a retrospective cohort study of adults with a history of arrhythmia in the Montefiore Health System (1 January 2016–17 August 2024). COVID-19 status [...] Read more.

Background/Objectives: Individuals with arrhythmia who survived COVID-19 could be susceptible to long-term cardiovascular complications and clinical outcomes. Methods: We performed a retrospective cohort study of adults with a history of arrhythmia in the Montefiore Health System (1 January 2016–17 August 2024). COVID-19 status was determined by a positive or negative polymerase-chain-reaction test. Outcomes included all-cause mortality, first-time myocardial infarction (MI), heart failure (HF), ischemic or hemorrhagic stroke, and major adverse cardiovascular events (MACE: defined as MI, HF, stroke, or death) > 30 days post-index date. Cox proportional hazards and Fine–Gray competing risk models, adjusted for demographic, clinical, socioeconomic, and COVID-19 vaccination variables, were employed. The association of outcomes with blood biomarkers taken at time of infection were also assessed in hospitalized COVID-19 patients. Results: Among the 6830 arrhythmia patients, 985 were hospitalized for COVID-19, 1591 were not hospitalized for COVID-19, and 4254 did not have COVID-19. Patients hospitalized for COVID-19 had a higher risk of all-cause mortality (adjusted hazard ratio = 2.90, 95% confidence-interval [2.08, 4.04]), first-time MI, HF, and MACE compared to controls without COVID-19. No increased risk was observed among non-hospitalized COVID-19-positive patients compared to controls, except for all-cause mortality. Older age, male sex, Medicaid, and significant comorbidities were associated with the risk of MACE. Elevated levels of creatinine, lactate dehydrogenase, D-dimer, neutrophil-to-lymphocyte ratio, low hemoglobin, and low left ventricular ejection fraction during infection were associated with higher future MACE risk. Conclusions. In individuals with arrhythmia, severe COVID-19 is associated with increased long-term risks of mortality and new-onset cardiovascular complications, while mild infection with mortality risk. These findings highlight the need for long-term cardiovascular monitoring in this population. Full article

(This article belongs to the Special Issue Diagnosis and Prognosis of Heart Disease, 2nd Edition)

► Show Figures

Figure 1

14 pages, 2196 KB

Open AccessEditor’s ChoiceArticle

Prospective, Multicentre Feasibility Study of Remote Colon Capsule Endoscopy Using the OMOM CC100 System

by Alexandra Agache, Ervin Toth, Niels Qvist, Miguel Mascarenhas, Wojciech Marlicz, Benedicte Schelde-Olesen, Miguel Mascarenhas-Saraiva, Maria Marlicz, Gabriele Wurm Johansson, Artur Nemeth and Anastasios Koulaouzidis

Diagnostics 2026, 16(1), 20; https://doi.org/10.3390/diagnostics16010020 - 20 Dec 2025

Viewed by 1454

Abstract

Background and Aims: Colon capsule endoscopy (CCE) provides a non-invasive alternative to traditional colonoscopy. This study evaluated the feasibility, safety, diagnostic yield (DY), and patient satisfaction of the OMOM CC100 CCE system, with special focus on fully remote (n = 30) and [...] Read more.

Background and Aims: Colon capsule endoscopy (CCE) provides a non-invasive alternative to traditional colonoscopy. This study evaluated the feasibility, safety, diagnostic yield (DY), and patient satisfaction of the OMOM CC100 CCE system, with special focus on fully remote (n = 30) and partially remote (n = 89) administration across four centres to advance decentralised models. Methods: This prospective, investigator-initiated, international multicentre feasibility study enrolled 119 patients aged 18–75 years at centres in Denmark, Sweden, Portugal, and Poland from July 2024 to May 2025. Indications included rectal bleeding, iron-deficiency anaemia, a positive faecal immunochemical test, changes in bowel habit, suspected inflammatory bowel disease (IBD), post-polypectomy or colorectal cancer (CRC) surgery surveillance, and a family history of CRC. The OMOM CC100 capsule was employed with a standardised bowel preparation regimen. Administration was fully remote in Denmark using the IntelliGI™ platform and partially remote (clinic ingestion, home completion) at the other sites. Primary outcomes encompassed procedure feasibility, completion rate (capsule excretion or anal verge visualisation), bowel cleanliness (Leighton-Rex scale ≥ 3), diagnostic yield, and patient satisfaction. Secondary measures included transit times, adverse events, and technical failures. Results: Median age was 55.7 years (65 males, 54 females). Overall completion rate was 79%, varying by centre: Sweden (90%), Portugal (81%), Denmark (80%), and Poland (63%). Adequate bowel cleanliness was achieved in 71% of cases. Diagnostic findings included polyps (25 patients), angioectasia (20), diverticulosis (17), and mucosal inflammation (17); 42% were normal. Fully remote administration yielded 80% completion and 89.7% satisfaction. No serious adverse events occurred; overall satisfaction was 81%, with 87% preferring home-based procedures. Conclusions: The OMOM CC100 CCE system is feasible, safe, with DY comparable to established systems. IntelliGI™-enabled remote administration promotes decentralised care, enhancing accessibility. Full article

(This article belongs to the Special Issue New Advances in Digestive Endoscopy)

► Show Figures

Figure 1

13 pages, 826 KB

Open AccessEditor’s ChoiceArticle

Risks of Stroke and Transient Cerebral Ischemia up to 4 Years Post-SARS-CoV-2 Infection in Large Diverse Urban Population in the Bronx

by Sagar Changela, Roham Hadidchi, Aditi Vichare, Liora Rahmani, Sonya Henry and Tim Q. Duong

Diagnostics 2025, 15(24), 3183; https://doi.org/10.3390/diagnostics15243183 - 13 Dec 2025

Cited by 2 | Viewed by 2988

Abstract

Background: SARS-CoV-2 infection could trigger hypercoagulation and hyperinflammation that may predispose patients to cerebrovascular events. The long-term risk of stroke among COVID-19 patients remains unclear. This study investigated the long-term risks of ischemic stroke and transient cerebral ischemia (TCI) among patients with and [...] Read more.

Background: SARS-CoV-2 infection could trigger hypercoagulation and hyperinflammation that may predispose patients to cerebrovascular events. The long-term risk of stroke among COVID-19 patients remains unclear. This study investigated the long-term risks of ischemic stroke and transient cerebral ischemia (TCI) among patients with and without COVID-19. Methods: We conducted an observational cohort study in the Montefiore Health System (February 2020–January 2024), with 52,117 COVID+ and 837,395 COVID− patients without prior cerebrovascular events. Demographics, comorbidities, insurance, unmet social needs, and median income were adjusted for using inverse probability weighting. Cox-proportional regression hazard ratios (HR) and their 95% confidence intervals were computed for ischemic stroke and TCI. Results: Compared to COVID− controls, ischemic stroke risk was higher among hospitalized COVID+ patients (HR = 1.32 [1.12–1.55]) and non-hospitalized COVID+ patients (1.21 [1.05–1.39]). Compared to COVID− controls, TCI risk was similar among hospitalized COVID+ patients (1.00 [0.75–1.33]), but higher among non-hospitalized COVID+ patients (2.15 [1.81–2.56]). Conclusions: Hospitalized and non-hospitalized COVID-19 patients had a higher long-term risk of ischemic stroke while only non-hospitalized COVID-19 patients had a higher long-term risk of TCI. These findings underscore the needs for long-term monitoring of cerebrovascular risk factors in COVID-19 survivors. Full article

(This article belongs to the Special Issue Neurological Diseases: Biomarkers, Diagnosis and Prognosis)

► Show Figures

Figure 1

15 pages, 915 KB

Open AccessEditor’s ChoiceArticle

Executive Functions and Subjective Cognitive Decline: The Moderating Role of Depressive Symptoms

by Marina Maffoni, Annalisa Magnani, Antonia Pierobon, Alessandra Mafferra, Fabrizio Pasotti, Carlo Dallocchio, Valeria Torlaschi, Daniela Mancini and Cira Fundarò

Diagnostics 2025, 15(24), 3164; https://doi.org/10.3390/diagnostics15243164 - 11 Dec 2025

Cited by 1 | Viewed by 1283

Abstract

Background: Executive dysfunction may be an early marker of neurodegenerative disorders, even if it is difficult to detect objectively. Subjective cognitive decline (SCD) may reflect subtle deficits in executive functions (EFs); however, SCD is also strongly influenced by affective factors such as [...] Read more.

Background: Executive dysfunction may be an early marker of neurodegenerative disorders, even if it is difficult to detect objectively. Subjective cognitive decline (SCD) may reflect subtle deficits in executive functions (EFs); however, SCD is also strongly influenced by affective factors such as depression. Whether depressive symptoms alter the link between EFs and SCD remains unclear. The present study tested whether depressive symptoms moderate the association between executive functioning and SCD. Methods: In this cross-sectional study, 65 outpatients completed a comprehensive assessment including executive functions (FAB), self-reported cognitive difficulties (CFI self-report), and depressive symptoms (PHQ-9). Descriptive statistics were performed, as well as a moderation analysis using PHQ-9 as moderator of the relationship between FAB and CFI self-report. Results: Participants (age: 69.28 ± 9.03) showed preserved EFs (FAB = 15.42, SD = 2.11), mild depressive symptoms (PHQ-9 = 6.57, SD = 5.02), and modest subjective difficulties (CFI = 4.87, SD = 2.57). The FAB main effect was positive but non-significant (β = 0.155, p = 0.266), while PHQ-9 was a significant positive predictor (β = 0.470, p ≤ 0.001). The interaction effect was significant (95% CI: [−0.166, −0.015], β = −0.343, p = 0.020). Specifically, simple slope analysis showed that at low levels of depression (−1 SD), better executive functioning was associated with higher SCD (β = 0.498, p = 0.039). Instead, the association was negative but non-significant at moderate (β = 0.155, p = 0.266) and high levels of depression (+1 SD) (β = −0.188, p = 0.229). Conclusions: In SCD, depressive symptoms are a stronger correlate of subjective cognitive difficulties than executive functions. Moreover, higher depression may modulate the executive functions–complaint link, reducing and potentially reversing it as symptom burden increases. Screening and treatment of depressive symptoms should be integrated into SCD assessment and care. Longitudinal and multicenter studies are needed to more deeply understand these preliminary results. Full article

(This article belongs to the Special Issue Subjective Experiences of Decline and Dementia Risk: Cognitive, Functional, and Emotional Predictors of Cognitive Decline)

► Show Figures

Figure 1

25 pages, 4011 KB

Open AccessEditor’s ChoiceReview

MRI of the Scrotum and Penis: Current Applications and Clinical Relevance

by Bartosz Regent, Karolina Nowak, Katarzyna Skrobisz, Marcin Matuszewski and Michał Studniarek

Diagnostics 2025, 15(24), 3134; https://doi.org/10.3390/diagnostics15243134 - 9 Dec 2025

Cited by 1 | Viewed by 5060

Abstract

Background: Magnetic resonance imaging (MRI) plays an increasingly important role in the evaluation of scrotal and penile disorders, complementing ultrasonography in cases where findings are equivocal or complex. With its superior soft-tissue contrast, multiplanar capability, and advanced functional sequences, MRI provides unparalleled anatomic [...] Read more.

Background: Magnetic resonance imaging (MRI) plays an increasingly important role in the evaluation of scrotal and penile disorders, complementing ultrasonography in cases where findings are equivocal or complex. With its superior soft-tissue contrast, multiplanar capability, and advanced functional sequences, MRI provides unparalleled anatomic and tissue characterization across a wide range of male genital pathologies. Summary: This review summarizes current clinical applications of MRI in scrotal and penile imaging and discusses its diagnostic value, protocol optimization, and interpretive features. In scrotal pathology, MRI accurately differentiates torsion, trauma, infection, and neoplasms, aiding in the distinction between benign and malignant testicular lesions and supporting testis-sparing management. Quantitative diffusion and perfusion metrics further refine lesion characterization. In andrology, MRI biomarkers such as apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR), and proton spectroscopy serve as promising non-invasive indicators of spermatogenic activity in male infertility. In penile imaging, MRI enables precise local staging of carcinoma, assessment of plaque morphology and activity in Peyronie’s disease, evaluation of tissue viability in priapism, and detection of prosthesis-related complications. Conclusions: MRI has become an essential problem-solving tool in the assessment of scrotal and penile diseases, enhancing diagnostic confidence and surgical planning. Future directions include protocol standardization, quantitative parameter validation, and the integration of radiomics and artificial intelligence to improve reproducibility and clinical impact. Full article

(This article belongs to the Special Issue Innovations in Medical Imaging for Precision Diagnostics)

► Show Figures

Figure 1

18 pages, 3614 KB

Open AccessEditor’s ChoiceArticle

Post-Surgical Reassessment of Breast Cancer IHC: Concordance, Δ-Metrics, and Treatment-Relevant Reclassification

by Ramona Andreea Cioroianu, Michael Schenker, Tradian Ciprian Berisha, Virginia-Maria Rădulescu, George Ovidiu Cioroianu, Raluca Chirculescu, Ana Maria Petrescu, Mihaela Popescu, Anda Lorena Dijmărescu and Stelian Ștefăniță Mogoantă

Diagnostics 2025, 15(24), 3128; https://doi.org/10.3390/diagnostics15243128 - 9 Dec 2025

Viewed by 772

Abstract

Background/Objectives: Immunohistochemical (IHC) profiles assessed on core biopsies guide initial therapy in breast cancer; however, paired changes between biopsy and surgical specimens may alter treatment pathways. We aimed to quantify paired biomarker dynamics (ER, PR, HER2, Ki-67) and the proportion of patients [...] Read more.

Background/Objectives: Immunohistochemical (IHC) profiles assessed on core biopsies guide initial therapy in breast cancer; however, paired changes between biopsy and surgical specimens may alter treatment pathways. We aimed to quantify paired biomarker dynamics (ER, PR, HER2, Ki-67) and the proportion of patients undergoing clinically actionable reclassification. Methods: We conducted a single-center retrospective study of 79 patients with paired pre- and post-surgical IHC for ER, PR, HER2 (0/1+/2+/3+ with reflex ISH for 2+), and Ki-67 (20% cut-off). Paired categorical shifts were tested with McNemar’s test; agreement was quantified using Cohen’s κ (95% CI); and multivariable logistic regression examined correlates of neoadjuvant chemotherapy (NACT). Two-sided p < 0.05 denoted statistical significance. Results: Post-surgical reassessment showed measurable conversions: PR-negative increased from 15.19% to 27.85%, while PR-positive decreased 84.81%→72.15%; HER2 3+ contracted 11.39%→6.33% with a parallel rise in 2+ (equivocal) 17.72%→24.05%; Ki-67 < 20% rose 37.97%→56.96%, whereas the >30% category was absent post-surgery. McNemar tests indicated significant paired shifts for PR (p = 0.016) and Ki-67 (p = 0.009); agreement was substantial for ER (κ = 0.70) and lower for PR (κ = 0.49), HER2 (κ = 0.43), and Ki-67 (κ = 0.29). High proliferation (Ki-67 ≥ 20%) independently predicted NACT (OR = 4.36, 95% CI 1.48–12.80). Conclusions: Paired IHC reassessment from biopsy to surgery reveals biomarker conversions that can reclassify therapeutic eligibility (e.g., anti-HER2 candidacy, endocrine strategies). These data support selective confirmation of IHC on resection specimens in routine practice and provide Δ-metrics to inform decision-making; external validation in prospective cohorts is warranted. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

► Show Figures

Figure 1

18 pages, 361 KB

Open AccessEditor’s ChoiceReview

Clinical Benefits and Limitations of Cone-Beam Computed Tomography in Endodontic Practice: A Contemporary Evidence-Based Review

by Jasmine Wong, Chengfei Zhang and Angeline Hui Cheng Lee

Diagnostics 2025, 15(24), 3117; https://doi.org/10.3390/diagnostics15243117 - 8 Dec 2025

Cited by 3 | Viewed by 3167

Abstract

Cone-beam computed tomography (CBCT) has transformed endodontic practice by enabling more precise diagnosis and treatment of pulpal and apical pathologies. The aim of this review was to summarize the current clinical applications, benefits and limitations of CBCT in endodontic practice. A search of [...] Read more.

Cone-beam computed tomography (CBCT) has transformed endodontic practice by enabling more precise diagnosis and treatment of pulpal and apical pathologies. The aim of this review was to summarize the current clinical applications, benefits and limitations of CBCT in endodontic practice. A search of electronic databases identified relevant literature on CBCT applications, innovations, and limitations. Emphasis was placed on identifying contemporary studies published in the last 5 years. In general, CBCT demonstrates better diagnostic efficacy across multiple applications, including identifying complex anatomy, detection of apical periodontitis, pre-surgical planning and the diagnosis and management of longitudinal root fractures, traumatic dental injuries and root resorptions. However, clinicians should balance the benefits of CBCT against its shortcomings, such as increased radiation exposure, presence of artifacts and higher costs. Proper use requires adherence to guidelines, optimized machine settings, and interpretation by trained individuals. Recent research explores the integration of CBCT with emerging technologies like artificial intelligence and guided systems. In summary, CBCT remains an essential tool for clinical decision-making in endodontics when used judiciously, with ongoing research continuing to expand its potential applications. Full article

(This article belongs to the Special Issue Application of Cone Beam Computed Tomography for Maxillofacial Diseases, Third Edition)

26 pages, 5565 KB

Open AccessEditor’s ChoiceArticle

Explainable Federated Learning for Multi-Class Heart Disease Diagnosis via ECG Fiducial Features

by Tanjila Alam Sathi, Rafsan Jany, AKM Azad, Salem A. Alyami, Naif Alotaibi, Iqram Hussain and Md Azam Hossain

Diagnostics 2025, 15(24), 3110; https://doi.org/10.3390/diagnostics15243110 - 7 Dec 2025

Cited by 1 | Viewed by 1819

Abstract

Background/Objectives: Cardiovascular disease (CVD) remains a leading cause of mortality and disability worldwide, with timely diagnosis critical for preventing long-term functional impairment. Electrocardiograms (ECGs) provide essential biomarkers of cardiac function, but their interpretation is often complex, particularly across multi-institutional datasets. Methods: This study [...] Read more.

Background/Objectives: Cardiovascular disease (CVD) remains a leading cause of mortality and disability worldwide, with timely diagnosis critical for preventing long-term functional impairment. Electrocardiograms (ECGs) provide essential biomarkers of cardiac function, but their interpretation is often complex, particularly across multi-institutional datasets. Methods: This study presents an explainable federated learning framework with long short-term memory (FL-LSTM) for multi-class heart disease classification, capable of distinguishing arrhythmia, ischemia, and healthy states while preserving patient privacy. Results: The model was trained and evaluated on three heterogeneous ECG datasets, achieving 92% accuracy, 99% AUC, and 91% F1 score, outperforming existing federated approaches. Model interpretability is provided via SHapley Additive exPlanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME), highlighting clinically relevant ECG biomarkers such as P-wave height, R-wave height, QRS complex, RR interval, and QT interval. Conclusions: By integrating temporal modeling, federated learning, and interpretable AI, the framework enables secure and collaborative cardiac diagnosis while supporting transparent clinical decision-making in distributed healthcare settings. Full article

(This article belongs to the Special Issue AI and Digital Health for Disease Diagnosis and Monitoring, 2nd Edition)

► Show Figures

Figure 1

12 pages, 808 KB

Open AccessEditor’s ChoiceArticle

Lung Ultrasound Offers Fast and Reliable Exclusion of Heart Failure in the Emergency Department: A Prospective Diagnostic Study

by Adis Keranović, Katja Kudrna Prašek and Ivan Gornik

Diagnostics 2025, 15(24), 3100; https://doi.org/10.3390/diagnostics15243100 - 6 Dec 2025

Viewed by 1224

Abstract

Background/Objectives: Acute dyspnea is a common and urgent presentation in the emergency department, with acute heart failure (AHF) as one of its leading causes. Rapid differentiation between AHF and other etiologies is essential. Methods: This study aimed to evaluate the diagnostic [...] Read more.

Background/Objectives: Acute dyspnea is a common and urgent presentation in the emergency department, with acute heart failure (AHF) as one of its leading causes. Rapid differentiation between AHF and other etiologies is essential. Methods: This study aimed to evaluate the diagnostic accuracy of lung ultrasound (LUS) and compare it to chest X-ray (CXR) and NT-proBNP accuracy in patients with acute dyspnea, and to assess the potential of LUS for fast bedside diagnosis. This prospective study included 242 adult patients presenting with acute dyspnea of ≤3 days’ duration. All underwent NT-proBNP testing, CXR, and LUS according to a standardized protocol. The final diagnosis was established by experienced clinicians using all available clinical, laboratory, and imaging data, blinded to the LUS results. Diagnostic performance measures of LUS, CXR, and NT-proBNP were evaluated, and examination times of LUS and CXR were compared. Results: LUS achieved the highest sensitivity (95.3%) and negative predictive value (90.8%) for AHF, outperforming NT-proBNP (87.5%, 74.2%) and CXR (84.4%, 79.0%). CXR showed the highest specificity (65.8%) and positive predictive value (73.5%), while LUS specificity was moderate (51.8%). The LUS results were available significantly faster (median 10.0 min) than CXR (median 62.5 min). Conclusions: LUS demonstrated diagnostic accuracy comparable to CXR and NT-proBNP, with superior sensitivity, negative predictive value, and shorter time to results. These findings support its use as a rapid, non-invasive, first-line tool for excluding AHF in acute dyspnea patients. Full article

(This article belongs to the Special Issue Advances in Ultrasound)

► Show Figures

Figure 1

25 pages, 373 KB

Open AccessEditor’s ChoiceReview

Rapid Molecular Diagnostics for MDR Nosocomial Infections in ICUs: Integration with Prevention, Stewardship, and Novel Therapies

by Karina Cristina Marin, Stelian Adrian Ritiu, Adelina Băloi, Claudiu Rafael Barsac, Dorel Sandesc, Marius Papurica, Alexandru Florin Rogobete, Daiana Toma, Mirela Tamara Porosnicu, Ciprian Gindac, Madalina Butaș and Ovidiu Horea Bedreag

Diagnostics 2025, 15(23), 3060; https://doi.org/10.3390/diagnostics15233060 - 30 Nov 2025

Cited by 1 | Viewed by 1564

Abstract

Background/Objectives: Multidrug-resistant (MDR) nosocomial infections remain a major challenge in intensive care units (ICUs), where delays in diagnosis and suboptimal antimicrobial therapy significantly impact outcomes. This narrative review synthesizes international literature and local epidemiological data from Western Romania to examine the role [...] Read more.

Background/Objectives: Multidrug-resistant (MDR) nosocomial infections remain a major challenge in intensive care units (ICUs), where delays in diagnosis and suboptimal antimicrobial therapy significantly impact outcomes. This narrative review synthesizes international literature and local epidemiological data from Western Romania to examine the role of rapid molecular diagnostics in the management of MDR infections and their integration with prevention and antimicrobial stewardship (AMS) strategies. Methods: Evidence was collected through a narrative literature review using PubMed, WHO, and ECDC sources published between 2010 and 2025. Key terms included “rapid molecular diagnostics,” “sepsis,” “ICU,” “UNYVERO,” “GeneXpert,” “BioFire,” and “carbapenem resistance.” Studies were selected based on clinical relevance to rapid diagnostics and MDR pathogens; no PRISMA-based systematic methodology was applied. Results: Diagnostic performance varies by platform and clinical syndrome. UNYVERO Hospitalized Pneumonia panel demonstrates a sensitivity range of 88.8–91.4% and specificity of 94.9–99.5% in respiratory infections, with a turnaround time of approximately 4–5 h. The GeneXpert Carba-R assay identifies major carbapenemases within 45–60 min with reported sensitivity 96–100% and specificity of 93–99%. BioFire^® Pneumonia and Blood Culture Identification panels similarly provide rapid syndromic results within 1 h, enabling earlier optimization of antimicrobial therapy. Local ICU data from Western Romania identified a substantial burden of carbapenem-resistant Acinetobacter baumannii, underscoring the need for rapid resistance detection to guide therapy. Conclusions: Rapid molecular diagnostics, when integrated with prevention bundles and AMS programs, facilitate earlier targeted therapy, support responsible antimicrobial use, and improve clinical decision-making in MDR infections. Their value is amplified in settings with high resistance prevalence. Wider implementation, combined with surveillance and access to novel antimicrobials, is essential to improve outcomes in critically ill patients. Full article

(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)

23 pages, 1166 KB

Open AccessEditor’s ChoiceReview

Recent Trend of Laboratory Tests in Common Gastrointestinal Tract Disorders

by Terence A. Agbor and Waliul I. Khan

Diagnostics 2025, 15(23), 2998; https://doi.org/10.3390/diagnostics15232998 - 26 Nov 2025

Viewed by 2627

Abstract

The gastrointestinal (GI) tract is a complex organ system affected by multiple disorders with diverse etiologies ranging from infections to immune dysfunction disorders and cancers. Various GI disorders, such as Helicobacter pylori infection, inflammatory bowel disease (IBD), celiac disease, irritable bowel syndrome (IBS), [...] Read more.

The gastrointestinal (GI) tract is a complex organ system affected by multiple disorders with diverse etiologies ranging from infections to immune dysfunction disorders and cancers. Various GI disorders, such as Helicobacter pylori infection, inflammatory bowel disease (IBD), celiac disease, irritable bowel syndrome (IBS), and colon cancer, are common and cause significant morbidity, mortality, and healthcare costs. These disorders present with overlapping signs and symptoms, warranting the need for accurate laboratory diagnostic tests for appropriate treatment implementation and treatment monitoring. The gold standard confirmatory diagnostic test for most GI disorders is endoscopy and biopsy for histological analysis. Biomarkers in blood and stool are also routinely used either as first-line screening tests or for treatment monitoring in many GI disorders. This review summarizes common GI disorders along with related currently used clinical laboratory tests in screening, diagnosis, and monitoring of these diseases, outlining the methodology, utilization, advantages, and limitations of these tests. We also highlight the effectiveness of each test as well as the professional recommendations and clinical guidelines for their use where available. Finally, we shed some light on potential future tests and biomarkers that aid in diagnosing GI disorders and how these biomarkers can be used in conjunction to complement the current tests. Some of the potential future biomarkers discussed include the differential expression of gut microbiota and their respective metabolites, as well as cytokines, as potential tests that can be used to diagnose diseases, distinguish between disease subtypes, predict disease severity and occurrence, and optimize treatment decisions. Comprehending the effectiveness of various methodologies for laboratory diagnosis of GI disorders is crucial for health care personnel, including clinical laboratory professionals and clinicians, regarding testing options, test utilization, and interpretations of results. Insights into future tests in GI diseases in the context of microbiomes, metabolites, and immune mediators based on advanced technology are also important in their appropriate clinical utilization. Full article

(This article belongs to the Special Issue Recent Advances in Clinical Biochemistry, 2nd Edition)

► Show Figures

Figure 1

16 pages, 1850 KB

Open AccessEditor’s ChoiceArticle

Comprehensive Evaluation of a Point-of-Care Testing Platform for Decentralized Primary Healthcare: Ensuring Analytical Quality Through Central Laboratory Oversight

by Giacomo Moretti, Francesca Danila Alcaro, Luigi Colacicco and Andrea Urbani

Diagnostics 2025, 15(23), 2977; https://doi.org/10.3390/diagnostics15232977 - 24 Nov 2025

Viewed by 883

Abstract

Background/Objectives: Point-of-care testing (POCT) is increasingly adopted in primary healthcare to facilitate rapid screening and monitoring of chronic conditions. Ensuring that its analytical quality is comparable to central laboratory testing is crucial for safe and effective implementation. This study aims to rigorously evaluate [...] Read more.

Background/Objectives: Point-of-care testing (POCT) is increasingly adopted in primary healthcare to facilitate rapid screening and monitoring of chronic conditions. Ensuring that its analytical quality is comparable to central laboratory testing is crucial for safe and effective implementation. This study aims to rigorously evaluate the analytical performance of the Allegro POCT system against established central laboratory reference methods to determine its suitability for decentralized healthcare settings. Methods: We assessed the correlation, concordance, and bias of glycated hemoglobin (HbA1c), glucose (GLUC), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL), triglycerides (TRIG), creatinine (CREA), and C-reactive protein (CRP). Using a cohort of 100 residual patient samples, measurements from the Allegro POCT system were compared against reference methods on the Atellica CH 930 Analyzer and TOSOH G8 system. The statistical analysis was performed using Deming regression, Bland–Altman plots, and Pearson correlation. Results: HbA1c and GLUC demonstrated strong linearity and correlation (Pearson’s r = 0.9863 and r = 0.9994, respectively). A slight positive bias was noted for HbA1c at higher concentrations. In the lipid panel, CHOL showed a significant positive bias (mean bias +14.2 mg/dL), while TRIG exhibited a substantial negative bias (mean bias −37.0 mg/dL) and wide limits of agreement. HDL and CREA showed good linearity but only moderate agreement. CRP demonstrated excellent concordance with the reference method (Pearson’s r = 0.9955) and minimal bias. Conclusions: The Allegro system exhibits acceptable analytical performance for GLUC and CRP, rendering it suitable for decentralized use. HbA1c and CREA performance is adequate, though caution is advised due to observed biases. However, the significant biases for CHOL and TRIG underscore the indispensable role of central laboratory oversight in any POCT program. Rigorous initial validation and continuous quality monitoring under a robust governance framework are essential to ensure the reliability and clinical utility of POCT. Full article

(This article belongs to the Section Point-of-Care Diagnostics and Devices)

► Show Figures

Figure 1

19 pages, 4353 KB

Open AccessEditor’s ChoiceArticle

Genomic Characterization of Papillary Thyroid Carcinoma: Age Differences in Tumor Aggressiveness and Immune Infiltration

by Wei Ao, Shuqian Chen, Tenghong Liu, Bo Wang and Wenxin Zhao

Diagnostics 2025, 15(23), 2937; https://doi.org/10.3390/diagnostics15232937 - 21 Nov 2025

Cited by 1 | Viewed by 1200

Abstract

Background: Adolescents and young adults (AYA) with papillary thyroid carcinoma (PTC) often present with more extensive cervical lymph node metastasis (LNM) than older adults (AD). We aimed to identify age-associated molecular and immune features that might explain this phenotype and to explore potential [...] Read more.

Background: Adolescents and young adults (AYA) with papillary thyroid carcinoma (PTC) often present with more extensive cervical lymph node metastasis (LNM) than older adults (AD). We aimed to identify age-associated molecular and immune features that might explain this phenotype and to explore potential translational implications for managing aggressive AYA PTC. Methods: We analyzed clinical and transcriptomic data from 501 PTC cases in The Cancer Genome Atlas (TCGA), stratified as AYA (<30 years, n = 64) and AD (≥30 years, n = 437). An institutional RNA-seq cohort (n = 13; 7 AYA, 6 AD) was used to screen for differentially expressed genes (DEGs). DEGs were defined by p ≤ 0.05 and |log2 fold change| ≥ 1. Intersection with invasion- and dissemination-related gene sets yielded a final age-related DEG list. Functional enrichment (GO/KEGG via DAVID), PPI network analysis (STRING, Cytoscape/cytoHubba), and immune deconvolution (CIBERSORT LM22) were performed. Protein-level validation was carried out by immunohistochemistry (IHC) in an independent cohort (n = 56; 28 AYA, 28 AD). Statistical comparisons used chi-square/Fisher’s exact tests for categorical variables, t-tests or nonparametric tests for continuous variables, and EdgeR with FDR correction for transcriptomic analyses. Results: In TCGA, LNM was more frequent in AYA than in AD (62.1% vs. 47.8%, p = 0.031). From intersected analyses, we identified 239 core DEGs distinguishing highly invasive, age-related tumors. Key upregulated genes in AYA included CXCR4, OPCML and S100A2; downregulated genes included ATP1A3, CHL1, HLA-DRA and IL-1β. Enriched pathways involved extracellular matrix organization, cell adhesion, calcium signaling and canonical oncogenic cascades (PI3K-Akt, MAPK, Wnt, Ras). Immune deconvolution showed reduced naïve B cells, M1 and M2 macrophages and resting mast cells and an increased proportion of M0 macrophages in AYA tumors. IHC validated differential protein expression for seven markers. Collectively, the data indicate an immune-suppressed, immune-excluded microenvironment in AYA PTC. Conclusions: AYA PTC exhibits distinct molecular and immune features that may underlie its propensity for lymphatic dissemination. These findings support evaluation of translational strategies, such as CXCR4 inhibition, restoration of antigen presentation, and macrophage reprogramming, to convert “cold” tumors into immune-permissive lesions. Validation in larger, prospective, multicenter cohorts is required. Full article

(This article belongs to the Special Issue Recent Advances in Endocrinology Pathology)

► Show Figures

Figure 1

14 pages, 3548 KB

Open AccessEditor’s ChoiceArticle

Characterization of Peripheral Retinal Degenerations and Rhegmatogenous Lesions Using Ultra-Widefield Swept Source OCT Integrated with a Novel Scanning Laser Ophthalmoscope

by Daniela Bacherini, Clara Rizzo, Giulio Vicini, Diego Luciani, Lorenzo Vannozzi, Gianni Virgili, Fabrizio Giansanti and Cristina Nicolosi

Diagnostics 2025, 15(22), 2930; https://doi.org/10.3390/diagnostics15222930 - 20 Nov 2025

Cited by 2 | Viewed by 1412

Abstract

Background/Objectives: The purpose of this study was to evaluate the implementation of ultra-widefield swept-source optical coherence tomography (SS-OCT) in characterizing peripheral retinal degenerations and rhegmatogenous lesions, and to assess its potential implications for clinical management. These lesions are often challenging to visualize [...] Read more.

Background/Objectives: The purpose of this study was to evaluate the implementation of ultra-widefield swept-source optical coherence tomography (SS-OCT) in characterizing peripheral retinal degenerations and rhegmatogenous lesions, and to assess its potential implications for clinical management. These lesions are often challenging to visualize with conventional techniques, highlighting the need for advanced imaging modalities to improve detection and characterization. Methods: We conducted a retrospective observational study involving patients diagnosed with peripheral retinal degenerations and/or rhegmatogenous lesions referred to our center. All participants underwent comprehensive ophthalmological evaluation, including slit-lamp biomicroscopy, dilated fundus examination, and peripheral SS-OCT imaging. Key parameters assessed included the presence of vitreoretinal attachment, vitreous traction, full-thickness retinal defects, and subretinal fluid associated with the peripheral lesions under investigation. Results: A total of 107 eyes from 95 patients were included. The mean spherical equivalent was −2.18 ± 2.5 diopters, and mean BCVA was 0.03 ± 0.11. Peripheral SS-OCT imaging successfully captured and characterized 130 retinal lesions, including retinal tears (n = 34), lattice degeneration (n = 25), retinal holes (n = 21), peripheral retinoschisis (n = 17), and schisis/detachment (n = 7). Less commonly observed lesions were snail track degeneration (n = 4), white without pressure (n = 4) microcystic degeneration (n = 2), dialysis (n = 2), condensed vitreous (n = 2), and paving stone degeneration (n = 1). SS-OCT provided high-resolution visualization of the peripheral retina and vitreoretinal interface, revealing findings such as vitreous traction, everted edges in retinal holes, and associated subretinal fluid, some of which were not clinically detectable and, in several cases, directly influenced management decisions. Conclusions: Ultra-widefield SS-OCT significantly enhanced the visualization of peripheral retinal degenerations and rhegmatogenous lesions, providing clinically meaningful details that may influence diagnosis and clinical decision-making. Full article

(This article belongs to the Special Issue Novel Optical Imaging Technologies in Ophthalmology and Neuroscience: Advances and Applications)

► Show Figures

Figure 1

21 pages, 337 KB

Open AccessEditor’s ChoiceReview

The Interleukin Network in Sepsis: From Cytokine Storm to Clinical Applications

by Marcello Candelli, Marta Sacco Fernandez, Gloria Rozzi, Giorgio Sodero, Andrea Piccioni, Giulia Pignataro, Donato Rigante and Francesco Franceschi

Diagnostics 2025, 15(22), 2927; https://doi.org/10.3390/diagnostics15222927 - 19 Nov 2025

Cited by 5 | Viewed by 3060

Abstract

Background and Objectives: Despite major advances in medical science and critical care, sepsis remains a leading cause of morbidity and mortality worldwide: it arises from dysregulated host response to infections and may culminate in organ dysfunction. A hallmark of its pathogenesis is [...] Read more.

Background and Objectives: Despite major advances in medical science and critical care, sepsis remains a leading cause of morbidity and mortality worldwide: it arises from dysregulated host response to infections and may culminate in organ dysfunction. A hallmark of its pathogenesis is the cytokine storm, in which interleukins (ILs) serve as central mediators of both protective and deleterious immune responses. This review summarizes the current knowledge on the role of ILs in sepsis, emphasizing their potential as biomarkers and therapeutic targets. Material and Methods: We analyzed recent clinical and experimental studies focusing on the most studied ILs—including IL-1, IL-6, IL-10, IL-8, IL-12, IL-18, and IL-17—in the pathophysiology of sepsis. Attention was given to mechanistic insights, prognostic significance, and therapeutic strategies targeting IL pathways. Results: IL-1 and IL-6 emerged as key pro-inflammatory mediators, amplifying vascular permeability, coagulation activation, and shock, with IL-6 validated as a robust prognostic biomarker. IL-10 was identified as a pivotal anti-inflammatory cytokine, limiting tissue injury but fostering immunosuppression and secondary infections. Other ILs, such as IL-8, IL-12, IL-18, and IL-17, contributed to neutrophil recruitment, Th1/Th17 activation, organ-specific injury, and sepsis susceptibility. Therapeutic interventions targeting ILs, including the IL-1 receptor antagonist anakinra and IL-6 receptor blockade with tocilizumab, have shown promise in selected patient subgroups. Conclusions: ILs are central to the immunopathology of sepsis, acting both as drivers of hyperinflammation and mediators of immunosuppression. Their dual role underscores the relevance of ILs as diagnostic and prognostic biomarkers, as well as context-dependent therapeutic targets. Future approaches should prioritize precision immunomodulation aligned with the principles of personalized medicine to improve clinical outcomes in sepsis. Full article

(This article belongs to the Special Issue Early Diagnosis of Sepsis: Current Status and Challenges)

12 pages, 1075 KB

Open AccessEditor’s ChoiceArticle

Utility of REMS-Derived Fragility Score and Trabecular Bone Score in Evaluating Bone Health in Type 2 Diabetes Mellitus

by Antonella Al Refaie, Caterina Mondillo, Guido Cavati, Sara Gonnelli, Maria Dea Tomai Pitinca, Elena Ceccarelli, Paola Pisani, Luigi Gennari, Stefano Gonnelli and Carla Caffarelli

Diagnostics 2025, 15(22), 2877; https://doi.org/10.3390/diagnostics15222877 - 13 Nov 2025

Cited by 1 | Viewed by 947

Abstract

Background/Objectives: A significantly higher fracture risk characterizes Type 2 diabetes mellitus (T2DM) patients when compared to the non-diabetic population, even though their average bone mineral density (BMD) tends to be normal or high. This elevated risk is primarily driven by defective bone [...] Read more.

Background/Objectives: A significantly higher fracture risk characterizes Type 2 diabetes mellitus (T2DM) patients when compared to the non-diabetic population, even though their average bone mineral density (BMD) tends to be normal or high. This elevated risk is primarily driven by defective bone quality. The trabecular bone score (TBS) and radiofrequency echographic multispectrometry (REMS) have recently been proposed to improve the assessment of bone quality in T2DM individuals. This study aimed to evaluate whether TBS and REMS can improve the identification of osteoporosis and fracture risk in these patients. Methods: BMD was measured in 223 consecutive T2DM patients (126 women and 97 man) and 102 controls. BMD values for the lumbar spine (LS), femoral neck (FN), and total hip (TH) were obtained via both dual-energy X-ray absorptiometry (DXA) and radiofrequency echographic multi-spectrometry (REMS). In all patients, TBS and Fragility Score (FS) by REMS were measured and prior major osteoporotic fractures (MOF) were assessed. Results: All BMD T-scores measured by REMS were significantly lower than those obtained by DXA at both lumbar and femoral sites. T2DM patients with previous MOF exhibited lower T-scores for both BMD-LS and BMD-TH, as assessed by DXA and REMS, compared with patients without fractures. However, these differences reached statistical significance for BMD-TH with both techniques and for BMD-LS with REMS, but not for BMD-LS with DXA. Moreover, patients with a history of MOF had significantly lower TBS values (p < 0.05) and significantly higher FS values at both lumbar (p < 0.05) and femoral (p < 0.01) sites compared with those without fractures. Conclusions: The results of this study suggest that the parameters obtained using REMS technology (BMD and FS) may be valuable tools for improving the diagnosis of osteoporosis and assessing fracture risk in patients with T2DM. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Musculoskeletal Diseases and Bone Fracture Risk)

► Show Figures

Graphical abstract

27 pages, 1211 KB

Open AccessEditor’s ChoiceReview

Locally Advanced Cervical Cancer: Multiparametric MRI in Gynecologic Oncology and Precision Medicine

by Sara Boemi, Matilde Pavan, Roberta Siena, Carla Lo Giudice, Alessia Pagana, Marco Marzio Panella and Maria Teresa Bruno

Diagnostics 2025, 15(22), 2858; https://doi.org/10.3390/diagnostics15222858 - 12 Nov 2025

Cited by 1 | Viewed by 1703

Abstract

Background: Locally advanced cervical cancer (LACC) represents a significant challenge in oncology, requiring accurate assessment of local extent and metastatic spread. Multiparametric magnetic resonance imaging (mpMRI) has assumed a central role in the loco-regional characterization of the tumor due to its high soft-tissue [...] Read more.

Background: Locally advanced cervical cancer (LACC) represents a significant challenge in oncology, requiring accurate assessment of local extent and metastatic spread. Multiparametric magnetic resonance imaging (mpMRI) has assumed a central role in the loco-regional characterization of the tumor due to its high soft-tissue resolution and the ability to integrate functional information. Objectives: In this narrative review, we explore the use of mpMRI in the diagnosis, staging, and treatment response of LACC, comparing its performance with that of PET/CT, which remains complementary for remote staging. The potential of whole-body magnetic resonance imaging (WB-MRI) and hybrid PET/MRI techniques is also analyzed, as well as the emerging applications of radiomics and artificial intelligence. The paper also discusses technical limitations, interpretative variability, and the importance of protocol standardization. The goal is to provide an updated and translational summary of imaging in LACC, with implications for clinical practice and future research. Methods: Prospective and retrospective studies, systematic reviews, and meta-analyses on adult patients with cervical cancer were included. Results: Fifty-two studies were included. MRI demonstrated a sensitivity and specificity greater than 80% for parametrial and bladder invasion, but limited sensitivity (45–60%) for lymph node disease, lower than PET/CT. Multiparametric MRI was useful in early prediction of response to chemotherapy and radiotherapy and in distinguishing residual disease from fibrosis. The integration of MRI into Image-Guided Adaptive Brachytherapy (IGABT) resulted in improved oncological outcomes and reduced toxicity. The applications of radiomics and AI demonstrated enormous potential in predicting therapeutic response and lymph node status in the MRI study, but multicenter validation is still needed. Conclusions: MRI is the cornerstone of the local–regional staging of advanced cervical cancer; it has become an essential and crucial tool in treatment planning. Its use, combined with PET/CT for lymph node assessment and metastatic disease staging, is now the standard of care. Future prospects include the use of whole-body MRI and the development of predictive models based on radiomics and artificial intelligence. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

13 pages, 487 KB

Open AccessEditor’s ChoiceArticle

Clinical Relevance of Trace-Positive Results in Xpert MTB/RIF Ultra for Tuberculosis Diagnosis in a High-Burden Setting: A Retrospective Cohort Study

by Cristian Sava, Alin Iuhas, Cristian Marinău, Radu Galiș, Marius Rus and Mihaela Sava

Diagnostics 2025, 15(22), 2860; https://doi.org/10.3390/diagnostics15222860 - 12 Nov 2025

Cited by 2 | Viewed by 2258

Abstract

Background: The introduction of the “trace” category in the Xpert MTB/RIF Ultra assay has significantly improved the sensitivity of molecular tuberculosis diagnostics. While it enhances sensitivity, especially in paucibacillary and extrapulmonary cases, its specificity remains debatable, making its interpretation outside select populations [...] Read more.

Background: The introduction of the “trace” category in the Xpert MTB/RIF Ultra assay has significantly improved the sensitivity of molecular tuberculosis diagnostics. While it enhances sensitivity, especially in paucibacillary and extrapulmonary cases, its specificity remains debatable, making its interpretation outside select populations a topic of clinical uncertainty. Objectives: This study evaluates the diagnostic and clinical significance of trace-positive results obtained with the Xpert MTB/RIF Ultra assay in the context of a high-incidence TB setting, examining their association with clinical, imaging, and microbiological findings. Methods: A retrospective analysis was conducted on 65 samples with trace-positive Xpert Ultra results, collected over a six-year period from 59 distinct patients in a general hospital in Romania. Correlations were assessed with microscopy, culture, clinical features, imaging, treatment initiation, and prior TB history. A composite reference standard was used for diagnostic accuracy evaluation. Results: Of the 65 trace-positive samples, 29 (44.6%) were culture-positive and 5 (7.7%) were smear-positive. A high proportion of patients, 56 (94.9%), presented with TB-compatible symptoms, and 47 (79.6% of those with imaging) had highly suggestive radiological findings. Based on the composite reference standard, 47 patients (79.7%) were ultimately diagnosed with active TB. Anti-TB treatment was initiated in 44 patients (74.5%). Trace positivity was observed across various specimen types, including sputum, pleural fluid, and cerebrospinal fluid. Conclusions: In high TB burden environments, trace-positive Xpert Ultra results frequently reflect true disease when interpreted within the appropriate clinical and imaging framework. Our findings indicate that, in regions with high tuberculosis incidence such as Romania, trace-positive Xpert Ultra results may contribute meaningfully to clinical decision-making when interpreted alongside clinical and radiological findings, in alignment with current WHO guidance. Full article

(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)

► Show Figures

Figure 1

14 pages, 1040 KB

Open AccessEditor’s ChoiceArticle

Clinical Relevance and Follow-Up of Incidental CT Imaging Findings for COVID-19 Diagnosis: A Retrospective Analysis

by Marc Marty, Bjarne Kerber, Frederik Abel, Jonas Kroschke, Thomas Frauenfelder and Sabine Franckenberg

Diagnostics 2025, 15(22), 2832; https://doi.org/10.3390/diagnostics15222832 - 8 Nov 2025

Cited by 1 | Viewed by 1528

Abstract

Background/Objectives: The aim of this study was to evaluate the prevalence of incidental findings in thoracic computed tomography (CT) performed because of COVID-19 and their potential impact on patient management. Methods: This retrospective analysis included 683 CT scans from 327 patients [...] Read more.

Background/Objectives: The aim of this study was to evaluate the prevalence of incidental findings in thoracic computed tomography (CT) performed because of COVID-19 and their potential impact on patient management. Methods: This retrospective analysis included 683 CT scans from 327 patients who underwent CT imaging of the thorax with or without the application of intravenous contrast-agents because of the primary indication of COVID-19. Radiological findings were categorized according to the COVID-19 Pneumonia Imaging Classification by four independent readers. Incidental findings were categorized according to a scale ranging from 0 (no patient impairment) to 3b (severe permanent impairment). Results: In the 683 CT-scans, typical COVID-19 findings were present in 273 scans (40.0%), atypical signs in 97 (14.2%), indeterminate findings in 40 (5.9%), and no signs of COVID-19 in 273 (40.0%). Incidental findings were reported in 94 out of 683 cases (13.8%), of which 63 (67.0%) were classified as category 0, 12 (12.8%) as category 1, 9 (9.6%) as category 2a, none (0.0%) as category 2b, 5 (5.3%) as category 3a, and 5 (5.3%) as category 3b. Conclusions: CT scans of the thorax for COVID-19 show a small but significant number of incidental findings that require further investigation. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

12 pages, 809 KB

Open AccessEditor’s ChoiceArticle

The Clinical Relevance of Mast Cell Activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

by Johanna Rohrhofer, Lilian Ebner, Johannes Schweighardt, Michael Stingl and Eva Untersmayr

Diagnostics 2025, 15(22), 2828; https://doi.org/10.3390/diagnostics15222828 - 7 Nov 2025

Cited by 1 | Viewed by 7875

Abstract

Background/Objectives: Growing evidence suggests that mast cell activation (MCA) may contribute to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating disorder characterized by persistent fatigue and post-exertional malaise (PEM). Particularly in relation to orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (POTS), this study [...] Read more.

Background/Objectives: Growing evidence suggests that mast cell activation (MCA) may contribute to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating disorder characterized by persistent fatigue and post-exertional malaise (PEM). Particularly in relation to orthostatic intolerance (OI), including postural orthostatic tachycardia syndrome (POTS), this study aimed to investigate the prevalence and clinical relevance of MCA in an Austrian ME/CFS patient cohort. Methods: Two data sets were analyzed. The CCCFS data set, a comprehensive, patient-centered online questionnaire consisting of 687 filled surveys, focuses on patient stratification. Self-reported clinical features, disease progression, and treatment responses were analyzed. Preliminary findings were validated in a second, retrospective study, analyzing data of 383 Austrian ME/CFS patients with regard to MCA involvement and OI. Results: Among followed-up ME/CFS patients, MCA prevalence increased over the disease course, with up to 25.3% meeting the criteria for clinically relevant MCA. ME/CFS patients with Mast Cell Activation Syndrome (MCAS) and OI reported symptom alleviation significantly more often following mast cell-targeted treatment than those without MCAS (p < 0.0001). With regard to IF-channel inhibitors, ME/CFS patients diagnosed with MCAS responded more frequently than those without MCAS (p = 0.076), while no significant differences were observed in response to beta blockers (p = 0.637). In both cohorts, OI, particularly POTS, was significantly more common in patients with MCA involvement. Conclusions: MCA appears to be a frequent and clinically relevant comorbidity in ME/CFS and is associated with a higher prevalence of OI, particularly POTS. Stratifying patients based on MCA involvement may support personalized treatment approaches and improve clinical outcomes. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome: Clinical Diagnostics, Management, and Prognosis)

► Show Figures

Figure 1

21 pages, 1108 KB

Open AccessEditor’s ChoiceArticle

Sleep Trajectories in Amnestic and Non-Amnestic MCI: Longitudinal Insights from Subjective and Objective Assessments

by Areti Batzikosta, Despina Moraitou, Paschalis Steiropoulos, Elvira Masoura, Georgia Papantoniou, Ioanna-Giannoula Katsouri, Maria Sofologi, Glykeria Tsentidou and Magda Tsolaki

Diagnostics 2025, 15(21), 2815; https://doi.org/10.3390/diagnostics15212815 - 6 Nov 2025

Viewed by 1355

Abstract

Background/Objectives: Sleep disturbances are increasingly recognized as dynamic biomarkers of cognitive decline; however, longitudinal and multimodal studies directly comparing amnestic (aMCI) and non-amnestic mild cognitive impairment (naMCI) remain limited. Methods: In a three-wave longitudinal design (~24 months), 179 older adults (46 healthy controls [...] Read more.

Background/Objectives: Sleep disturbances are increasingly recognized as dynamic biomarkers of cognitive decline; however, longitudinal and multimodal studies directly comparing amnestic (aMCI) and non-amnestic mild cognitive impairment (naMCI) remain limited. Methods: In a three-wave longitudinal design (~24 months), 179 older adults (46 healthy controls [HCs], 75 aMCI, 58 naMCI; mean age = 70.2 years, education = 12.3 years) were assessed with actigraphy and validated questionnaires (Athens Insomnia Scale, Pittsburgh Sleep Quality Index, STOP-BANG). Mixed ANOVAs and structural equation modeling tested group, time and mediation effects. Results: Subjective measures revealed a progressive worsening of insomnia and sleep quality in MCI, with naMCI exhibiting the steepest decline, while HCs remained largely stable. STOP-BANG trajectories indicated increasing sleep-disordered breathing risk across groups, most pronounced in naMCI. Objective indices corroborated these findings: total sleep time (TST) and sleep efficiency (SE) declined significantly in MCI, especially naMCI, while wake after sleep onset (WASO) increased longitudinally. By the third assessment, naMCI consistently showed the shortest TST and lowest SE. Mediation analyses identified SE as a central predictor of future subjective complaints, with indirect contributions from WASO and PSQI. Conclusions: Longitudinal trajectories, rather than cross-sectional comparisons, best differentiated MCI subtypes. NaMCI demonstrated the most aggressive deterioration in both objective and subjective sleep measures, highlighting its heightened vulnerability to sleep dysregulation and potential relevance for neurodegenerative progression. Clinically, sustained monitoring of SE, TST, and sleep-disordered breathing risk may provide prognostic value and inform early, targeted interventions in at-risk populations. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

► Show Figures

Figure 1

16 pages, 2423 KB

Open AccessEditor’s ChoiceReview

Optimum Patient’s Selection for Atrial Fibrillation Ablation Using Echocardiography

by Matteo Cameli, Maria Concetta Pastore, Francesco Morrone, Giulia Elena Mandoli, Giovanni Benfari, Federica Ilardi, Matteo Lisi, Alessandro Malagoli, Simona Sperlongano, Ciro Santoro, Andrea Stefanini, Elena Placuzzi, Annalisa Pasquini, Miriam Durante, Aleksander Dokollari, Michael Y. Henein and Antonello D’Andrea

Diagnostics 2025, 15(21), 2793; https://doi.org/10.3390/diagnostics15212793 - 4 Nov 2025

Viewed by 1632

Abstract

Catheter ablation (CA) has become a validated technique for treating patients with symptomatic or paroxysmal atrial fibrillation (AF), as recommended by the latest 2024 European society of cardiology (ESC) guidelines, class II level A. The procedure is also recommended for patients with persistent [...] Read more.

Catheter ablation (CA) has become a validated technique for treating patients with symptomatic or paroxysmal atrial fibrillation (AF), as recommended by the latest 2024 European society of cardiology (ESC) guidelines, class II level A. The procedure is also recommended for patients with persistent AF without major risk factors for AF recurrence, as an alternative to antiarrhythmic medications class I or III. However, CA carries the risk of AF recurrence in 30–35% of patients, sometimes after the procedure. Multiple factors impact the onset, maintenance, and recurrence of AF after CA, including clinical, biohumoral, echocardiographic, genetic, and lifestyle factors. Beyond traditional predictors, emerging factors such as obstructive sleep apnea syndrome, chronic renal failure, chronic lung disease, physical activity patterns, gut microbiota composition, and epicardial fat thickness significantly influence outcomes. Therefore, optimizing patient’s selection for CA is an important strategy to minimize the risk of AF recurrence. Many echocardiographic parameters emerged as predictors of AF recurrence post-CA, but none stood out as a potential single factor. These factors include traditional markers such as left atrial size by 2D echocardiography, LV ejection fraction, LV diastolic function parameters as well as myocardial deformation addressed by the recently developed speckle tracking analysis. Additionally, the duration and type of AF represent fundamental risk factors, with longstanding persistent AF showing significantly higher recurrence rates compared to paroxysmal forms. Novel biomarkers including MR-proANP, caspase-8, hsa-miR-206, and neurotrophin-3 show promise in enhancing risk prediction capabilities. The aim of this review is to explore the most relevant echocardiographic parameters, including myocardial deformation, that could accurately predict recurrence of AF after CA, while also examining the role of emerging clinical and biochemical predictors in comprehensive patient selection strategies. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

20 pages, 15383 KB

Open AccessEditor’s ChoiceReview

Lung Ultrasound in Pediatrics: A Review with Core Principles That Every User Should Know

by Soultana Foutzitzi, Panos Prassopoulos, Athanasios Chatzimichail, Katerina Kambouri, Hippocrates Moschouris, Evlampia A. Psatha, Panagoula Oikonomou and Savas P. Deftereos

Diagnostics 2025, 15(21), 2782; https://doi.org/10.3390/diagnostics15212782 - 2 Nov 2025

Viewed by 3044

Abstract

Lung ultrasound (LUS) has emerged as a valuable diagnostic modality for the evaluation of respiratory disorders in neonates, infants and children. LUS has high diagnostic accuracy for identification of lung lesions in neonates, infants and children, where most lung lesions abut the pleura. [...] Read more.

Lung ultrasound (LUS) has emerged as a valuable diagnostic modality for the evaluation of respiratory disorders in neonates, infants and children. LUS has high diagnostic accuracy for identification of lung lesions in neonates, infants and children, where most lung lesions abut the pleura. Furthermore, LUS has the advantage of rapid execution and ease of use, and does not require ionizing radiation. Its sensitivity, cost-effectiveness, and clinical efficiency make it an important tool for supporting clinical decision-making and improving patient management. Moreover, LUS may represent a reliable alternative to chest radiography for the assessment of pediatric lung conditions and, in selected cases, could potentially replace routine chest X-rays (CXRs). Because LUS is a user-friendly technique that enables real-time imaging without radiation, it has increasingly been used in clinical practice in recent years. Here, we discuss the diagnostic role of LUS for the accurate identification of pulmonary lesions in pediatric patients. In addition, we present LUS sonographic findings associated with common pediatric lung diseases, including signs and artifacts that can be used during diagnosis and evaluation of pediatric patients. Full article

(This article belongs to the Section Point-of-Care Diagnostics and Devices)

► Show Figures

Figure 1

16 pages, 924 KB

Open AccessEditor’s ChoiceArticle

Transcervical, Transabdominal and Transvaginal Chorionic Villus Sampling for Prenatal Diagnosis in Zagreb, Croatia: A Prospective Single-Operator Study on 5500 Cases

by Petra Podobnik, Tomislav Meštrović, Mario Podobnik, Ivan Bertović-Žunec, Igor Lončar, Kristian Kurdija, Dženis Jelčić, Zlata Srebreniković and Slava Podobnik-Šarkanji

Diagnostics 2025, 15(21), 2750; https://doi.org/10.3390/diagnostics15212750 - 30 Oct 2025

Viewed by 1821

Abstract

Background/Objectives: Chorionic villus sampling (CVS) is a pivotal diagnostic tool for early prenatal detection of chromosomal and genetic abnormalities; however, the safety and diagnostic efficacy of different CVS approaches remain a subject of clinical interest. This monocentric study compares transcervical (TC-CVS), transabdominal [...] Read more.

Background/Objectives: Chorionic villus sampling (CVS) is a pivotal diagnostic tool for early prenatal detection of chromosomal and genetic abnormalities; however, the safety and diagnostic efficacy of different CVS approaches remain a subject of clinical interest. This monocentric study compares transcervical (TC-CVS), transabdominal (TA-CVS) and transvaginal (TV-CVS) techniques, focusing on procedure-related fetal loss and diagnostic yield. Methods: In this 15-year, single-operator prospective study, a total of 5500 women underwent CVS between 10 and 14 weeks of gestation at a single center. Sampling was performed via TA-CVS (n = 4500), TC-CVS (n = 850), or TV-CVS (n = 150). Outcomes assessed included fetal loss rates, sample adequacy, early complications and hemodynamic changes measured by Doppler ultrasound. A p-value < 0.05 (two-tailed) was considered statistically significant. Results: Spontaneous abortion rates were significantly lower following TA-CVS (0.18%; 8/4500) compared to TC-CVS (0.6%; 5/850) and TV-CVS (1.3%; 2/150) (χ² = 24.56, p < 0.001). Post hoc pairwise analysis showed significantly lower fetal loss in TA-CVS compared to TC-CVS, but not between TA-CVS and TV-CVS. Cytogenetic abnormalities were detected in 220 cases (4.0%), and clinically significant copy number variants (CNVs) were confirmed in fetuses with major structural malformations. Five-year follow-up showed no diagnosed intellectual disability among assessed children. Optimal tissue weight (10–20 mg) was more frequent with TA-CVS (66.7%) than TC-CVS (35.3%) or TV-CVS (36.7%) (χ² = 350.92, p < 0.001). In a Doppler subset (n = 400), uterine, spiral, and interplacental artery PI changes were non-significant; the umbilical (p = 0.032) and middle cerebral arteries (p < 0.001) showed transient PI reductions after sampling. Conclusions: Transabdominal CVS demonstrated the most favorable balance of safety and diagnostic quality, suggesting it should be the preferred first-line technique in early prenatal diagnosis. Standardized technique and operator training remain critical to optimize outcomes. Full article

(This article belongs to the Special Issue Diagnosis and Prognosis of Gynecological and Obstetric Diseases)

► Show Figures

Figure 1

13 pages, 4332 KB

Open AccessEditor’s ChoiceArticle

Brain Perfusion Scintigraphy in the Diagnostic Toolbox for the Confirmation of Brain Death: Practical Aspects and Examination Protocol

by Albrecht Günther, Anne Gunkel, Christian Geis, Dirk Brämer, Martin Brauer, Claus Doerfel, Michael Fritzenwanger, Martin Freesmeyer, Thomas Winkens, Robert Drescher and Anke Werner

Diagnostics 2025, 15(21), 2734; https://doi.org/10.3390/diagnostics15212734 - 28 Oct 2025

Viewed by 1500

Abstract

Background: In addition to clinical examinations, confirmatory investigations are frequently performed to determine brain death (BD). Among other perfusion tests, brain perfusion scintigraphy (BPS) has been shown to be a reliable tool for the detection of brain circulatory arrest, particularly in cases with [...] Read more.

Background: In addition to clinical examinations, confirmatory investigations are frequently performed to determine brain death (BD). Among other perfusion tests, brain perfusion scintigraphy (BPS) has been shown to be a reliable tool for the detection of brain circulatory arrest, particularly in cases with inconclusive clinical status or potential pharmacological interactions. Methods: Evaluation for brain death included standardized clinical examinations by two experienced neuro-intensive medicine specialists, followed by ancillary brain perfusion tests. BPS with the lipophilic tracer ^99mTc-hexamethylpropyleneamine oxime (HMPAO) was performed according to a standardized protocol. Imaging results, additional confirmatory test results, as well as clinical parameters were prospectively recorded. Results: BPS was performed in 30 patients (18 male, 12 female; median age 55.5 years, range 0.1–79.8 years). Eight patients underwent decompressive craniectomy (DC) prior to BD evaluation, three patients were supported by veno-arterial extracorporeal membrane oxygenation (vaECMO), and one patient by a left ventricular assist device (LVAD). The median interval between the initial brain-damaging event and BPS was 4.0 days (range 1–18 days). BPS demonstrated brain perfusion cessation in all patients. A concomitant single-photon emission computed tomography (SPECT) was required in one patient. There were no technical failures requiring a re-examination. Conclusions: BPS is a feasible, safe, and technically robust confirmatory test in BD diagnosis. BPS yielded unambiguous results, particularly in cases with inconclusive results of other ancillary tests, in neonates, young children and patients after DC. It is applicable to patients supported by LVAD and vaECMO. Full article

(This article belongs to the Special Issue Neurological Disorders: Diagnosis and Management)

► Show Figures

Figure 1

16 pages, 2776 KB

Open AccessEditor’s ChoiceArticle

Optical Coherence Tomography Angiography (OCTA) Captures Early Micro-Vascular Remodeling in Non-Melanoma Skin Cancer During Superficial Radiotherapy: A Proof-of-Concept Study

by Gerd Heilemann, Giulia Rotunno, Lisa Krainz, Francesco Gili, Christoph Müller, Kristen M. Meiburger, Dietmar Georg, Joachim Widder, Wolfgang Drexler, Mengyang Liu and Cora Waldstein

Diagnostics 2025, 15(21), 2698; https://doi.org/10.3390/diagnostics15212698 - 24 Oct 2025

Viewed by 1516

Abstract

Background/Objectives: This proof-of-concept study evaluated whether optical coherence tomography angiography (OCTA) can non-invasively capture micro-vascular alterations in non-melanoma skin cancer (NMSC) lesions during and after superficial orthovoltage radiotherapy (RT) using radiomics and vascular features analysis. Methods: Eight patients (13 NMSC lesions) [...] Read more.

Background/Objectives: This proof-of-concept study evaluated whether optical coherence tomography angiography (OCTA) can non-invasively capture micro-vascular alterations in non-melanoma skin cancer (NMSC) lesions during and after superficial orthovoltage radiotherapy (RT) using radiomics and vascular features analysis. Methods: Eight patients (13 NMSC lesions) received 36–50 Gy in 6–20 fractions. High-resolution swept-source OCTA volumes (1.1 × 10 × 10 mm³) were acquired from each lesion at three time points: pre-RT, immediately post-RT, and three months post-RT. Additionally, healthy skin baseline was scanned. After artifact suppression and region-of-interest cropping, (i) first-order and texture radiomics and (ii) skeleton-based vascular features were extracted. Selected features after LASSO (least absolute shrinkage and selection operator) were explored with principal-component analysis. An XGBoost model was trained to classify time points with 100 bootstrap out-of-bag validations. Kruskal–Wallis tests with Benjamini–Hochberg correction assessed longitudinal changes in the 20 most influential features. Results: Sixty-one OCTA volumes were analyzable. LASSO retained 47 of 103 features. The first two principal components explained 63% of the variance, revealing a visible drift of lesions from pre- to three-month post-RT clusters. XGBoost achieved a macro-averaged AUC of 0.68 ± 0.07. Six features (3 texture, 2 first order, 1 vascular) changed significantly across time points (adjusted p < 0.05), indicating dose-dependent reductions in signal heterogeneity and micro-vascular complexity as early as treatment completion, which deepened by three months. Conclusions: OCTA-derived radiomic and vascular signatures tracked RT-induced micro-vascular remodeling in NMSC. The approach is entirely non-invasive, label-free, and feasible at the point of care. As an exploratory proof-of-concept, this study helps to refine scanning and analysis protocols and generates knowledge to support future integration of OCTA into adaptive skin-cancer radiotherapy workflows. Full article

(This article belongs to the Collection Biomedical Optics: From Technologies to Applications)

► Show Figures

Figure 1

11 pages, 649 KB

Open AccessEditor’s ChoiceReview

A Narrative Review of Photon-Counting CT and Radiomics in Cardiothoracic Imaging: A Promising Match?

by Salvatore Claudio Fanni, Ilaria Ambrosini, Francesca Pia Caputo, Maria Emanuela Cuibari, Domitilla Deri, Alessio Guarracino, Camilla Guidi, Vincenzo Uggenti, Giancarlo Varanini, Emanuele Neri, Dania Cioni, Mariano Scaglione and Salvatore Masala

Diagnostics 2025, 15(20), 2631; https://doi.org/10.3390/diagnostics15202631 - 18 Oct 2025

Cited by 1 | Viewed by 3590

Abstract

Photon-counting computed tomography (PCCT) represents a major technological innovation compared to conventional CT, offering improved spatial resolution, reduced electronic noise, and intrinsic spectral capabilities. These advances open new perspectives for synergy with radiomics, a field that extracts quantitative features from medical images. The [...] Read more.

Photon-counting computed tomography (PCCT) represents a major technological innovation compared to conventional CT, offering improved spatial resolution, reduced electronic noise, and intrinsic spectral capabilities. These advances open new perspectives for synergy with radiomics, a field that extracts quantitative features from medical images. The ability of PCCT to generate multiple types of datasets, including high-resolution conventional images, iodine maps, and virtual monoenergetic reconstructions, increases the richness of extractable features and potentially enhances radiomics performance. This narrative review investigates the current evidence on the interplay between PCCT and radiomics in cardiothoracic imaging. Phantom studies demonstrate reduced reproducibility between PCCT and conventional CT systems, while intra-scanner repeatability remains high. Nonetheless, PCCT introduces additional complexity, as reconstruction parameters and acquisition settings significantly may affect feature stability. In chest imaging, early studies suggest that PCCT-derived features may improve nodule characterization, but existing machine learning models, such as those applied to interstitial lung disease, may require recalibration to accommodate the new imaging paradigm. In cardiac imaging, PCCT has shown particular promise: radiomic features extracted from myocardial and epicardial tissues can provide additional diagnostic insights, while spectral reconstructions improve plaque characterization. Proof-of-concept studies already suggest that PCCT radiomics can capture myocardial aging patterns and discriminate high-risk coronary plaques. In conclusion, evidence supports a growing synergy between PCCT and radiomics, with applications already emerging in both lung and cardiac imaging. By enhancing the reproducibility and richness of quantitative features, PCCT may significantly broaden the clinical potential of radiomics in computed tomography. Full article

(This article belongs to the Special Issue Cardiothoracic Imaging: Recent Techniques and Applications in Diagnostics, Third Edition)

► Show Figures

Figure 1

17 pages, 322 KB

Open AccessEditor’s ChoiceReview

From Fluid Responsiveness to Prognosis: The Emerging Role of Point-of-Care Echocardiography in Sepsis

by Andrea Piccioni, Gloria Rozzi, Giacomo Spaziani, Michela Novelli, Mariella Fuorlo, Marcello Candelli, Giulia Pignataro, Luca Santarelli, Marcello Covino, Antonio Gasbarrini and Francesco Franceschi

Diagnostics 2025, 15(20), 2612; https://doi.org/10.3390/diagnostics15202612 - 16 Oct 2025

Cited by 2 | Viewed by 2449

Abstract

Sepsis is a life-threatening condition that requires early recognition and intervention to improve patient outcomes. Optimizing hemodynamic management is crucial, and clinicians must utilize all available tools to guide therapy effectively. Echocardiography is a rapid, non-invasive, and repeatable method that has emerged as [...] Read more.

Sepsis is a life-threatening condition that requires early recognition and intervention to improve patient outcomes. Optimizing hemodynamic management is crucial, and clinicians must utilize all available tools to guide therapy effectively. Echocardiography is a rapid, non-invasive, and repeatable method that has emerged as a valuable tool in the management of septic patients. Studying its role can provide insights into both therapeutic guidance and prognostic assessment. The primary aim of this review is to highlight the importance of echocardiography in the hemodynamic management of patients with sepsis. The secondary objective is to assess its prognostic value, as echocardiography can inform both the immediate management of critically ill patients and their overall prognosis. A narrative review of the literature published in the last 15 years was conducted using PubMed, and references were managed with Mendeley. Articles focusing on adult and pediatric patients, as well as relevant animal studies, which evaluated echocardiographic assessment of cardiac function, fluid responsiveness, or hemodynamic management were included. Multiple studies demonstrate that echocardiography is a reliable, non-invasive, and easily repeatable tool for assessing fluid responsiveness in septic patients. It allows for dynamic monitoring of stroke volume, VTI, and other hemodynamic parameters, supporting tailored fluid and vasoactive therapy. Additionally, echocardiography provides prognostic insights, with right ventricular dysfunction emerging as a strong predictor of increased mortality. Other parameters, including global longitudinal strain and left ventricular diastolic function, further contribute to risk stratification. Echocardiography is an indispensable tool in the management of sepsis, offering both real-time guidance for hemodynamic optimization and valuable prognostic information. Its routine use can enhance personalized care and improve clinical outcomes in critically ill septic patients. Full article

(This article belongs to the Section Point-of-Care Diagnostics and Devices)

23 pages, 3084 KB

Open AccessEditor’s ChoiceSystematic Review

Patterns of Lateral Lymph Node Involvement by Neck Level in cNIb Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis

by Dana M. Hartl, Karthik N. Rao, Andrés Coca Pelaz, Alessandra Rinaldo, Mark E. Zafereo, Greg W. Randolph, Iain J. Nixon, Marc Hamoir, K. Thomas Robbins, Luiz P. Kowalski, Pia Pace Asciak, Badr Soudi, Juan P. Rodrigo and Alfio Ferlito

Diagnostics 2025, 15(20), 2613; https://doi.org/10.3390/diagnostics15202613 - 16 Oct 2025

Viewed by 2165

Abstract

Background/Objectives: The optimal extent of lateral lymph node dissection in cN1b differentiated thyroid cancer remains controversial. This systematic review aimed to assess the frequency of lymph node involvement across neck levels I to V. Materials and Methods: A systematic review was conducted following [...] Read more.

Background/Objectives: The optimal extent of lateral lymph node dissection in cN1b differentiated thyroid cancer remains controversial. This systematic review aimed to assess the frequency of lymph node involvement across neck levels I to V. Materials and Methods: A systematic review was conducted following PRISMA guidelines. PubMed was searched for studies on lateral neck dissection in differentiated thyroid cancer. Included studies reported level-specified metastatic rates. Data on patient numbers and metastatic events were extracted. A random-effects meta-analysis with Freeman–Tukey double arcsine transformation was performed for each neck level to calculate pooled prevalence proportions and 95% confidence intervals. Heterogeneity was assessed using the I² statistic. Results: Meta-analysis of 57 studies revealed that level III (68%, 95% CI: 63–73) and level IV (66%, 95% CI: 61–70) had the highest metastatic prevalence, followed by level IIA (46%, 95% CI: 37–56). Level V demonstrated an overall prevalence of 22% (95% CI: 18–26), with sublevel VB (19%, 95% CI: 11–28) significantly higher than VA (4%, 95% CI: 1–9). Level I (6%, 95% CI: 2–11) and sublevel IIB (14%, 95% CI: 9–20) showed the lowest risk. Significant heterogeneity (I² 71–94%) was observed across all levels. Conclusions: Our findings support sparing level I, and sublevels IIB and VA during lateral neck dissection. Current guidelines recommend systematic dissection of IIA, III, IV, and VB, although VB involvement was found to be only 19% in our study. Future personalization of the extent of neck dissection, based on individual risk factors, may be key to optimizing oncologic and functional outcomes. Full article

(This article belongs to the Special Issue Advances in Molecular Pathology and Imaging for Precision Diagnosis and Treatment of Tumors)

► Show Figures

Figure 1

16 pages, 2562 KB

Open AccessEditor’s ChoiceArticle

Skeletal Muscle ³¹P Magnetic Resonance Spectroscopy Study of Patients with Parkinson’s Disease: Energy Metabolism and Exercise Performance

by Jimin Ren, Neha Patel, Talon Johnson, Ross Querry and Staci Shearin

Diagnostics 2025, 15(20), 2573; https://doi.org/10.3390/diagnostics15202573 - 13 Oct 2025

Cited by 1 | Viewed by 2239

Abstract

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremor, bradykinesia, rigidity, and postural instability. In the absence of disease-modifying therapies, exercise remains one of the few interventions shown to effectively reduce fall risk and improve mobility. [...] Read more.

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremor, bradykinesia, rigidity, and postural instability. In the absence of disease-modifying therapies, exercise remains one of the few interventions shown to effectively reduce fall risk and improve mobility. However, it remains unclear whether skeletal muscle ATP metabolism is impaired in PD, and whether the benefits of exercise arise primarily from improvements in central motor control or peripheral metabolic adaptations. Methods: Fourteen individuals with PD and five healthy controls underwent kinetic ³¹P Magnetic Resonance Spectroscopy (MRS) to assess resting muscle ATP synthesis and dynamic ³¹P MRS during in-magnet exercise to evaluate oxidative phosphorylation in active muscle. Results: At rest, ATP synthesis rates mediated by ATPase and creatine kinase (CK) were on average 46 ± 23% and 24 ± 9% lower, respectively, in the PD group compared to controls (p < 0.005), suggesting peripheral mitochondrial dysfunction. During plantar flexion exercise at 15% of lean body mass, range of motion (ROM) was reduced by 22 ± 5% in PD participants (p = 0.01). Despite this, post-exercise recovery of phosphocreatine (PCr) and inorganic phosphate (Pi) was similar between groups. Recovery time constants for PCr and Pi correlated with participants’ total weekly exercise time, indicating a metabolic adaptation to regular physical activity. Modest ROM improvements were observed in both groups following calf-raise exercise training. Conclusions: Reduced skeletal muscle ATP metabolism may contribute to peripheral weakness in PD. Regular exercise appears to promote adaptive metabolic responses, highlighting the need for therapeutic strategies targeting both central and peripheral components of PD. Full article

(This article belongs to the Special Issue Applications of Quantitative MRI in Neurodegenerative Disorders and Peripheral Neuropathies)

► Show Figures

Figure 1

16 pages, 3586 KB

Open AccessEditor’s ChoiceArticle

Ultrasound Risk Stratification of Autonomously Functioning Thyroid Nodules: Cine Loop Video Sequences Versus Static Image Captures

by Larissa Rosenbaum, Martin Freesmeyer, Tabea Nikola Schmidt, Christian Kühnel, Falk Gühne and Philipp Seifert

Diagnostics 2025, 15(19), 2525; https://doi.org/10.3390/diagnostics15192525 - 6 Oct 2025

Viewed by 1586

Abstract

Background/Objectives: Autonomously functioning thyroid nodules (AFTNs) are most frequently diagnosed as benign. However, they show high ratings in ultrasound (US) risk stratification systems (RSSs) that utilize the current clinical standard methodology of conventional static image capture (SIC) documentation. The objective of this [...] Read more.

Background/Objectives: Autonomously functioning thyroid nodules (AFTNs) are most frequently diagnosed as benign. However, they show high ratings in ultrasound (US) risk stratification systems (RSSs) that utilize the current clinical standard methodology of conventional static image capture (SIC) documentation. The objective of this study was to evaluate the RSS ratings and respective fine needle cytology (FNC) recommendations of cine loop (CL) video sequences in comparison to SIC. Methods: 407 patients with 424 AFTNs were enrolled in this unicentric, retrospective study between 11/2015 and 11/2023. Recorded US CL and SIC were analyzed lesion-wise and compared regarding US features, Kwak and ACR TIRADS, ACR FNC recommendations, as well as assessment difficulties and artifacts. Statistical analyses were conducted using the Chi² test and Spearman’s correlation coefficient in SPSS software. p-values < 0.05 were considered significant. Results: Strong to very strong correlations were observed for all US features, RSS ratings, and ACR FNC recommendations (Spearman’s correlation: each p < 0.001), comparing CL and SIC. For >60% of the AFTNs, ACR FNC recommendation was given. Kwak TIRADS were more consistent with the benign nature of AFTNs than the ACR ratings. CL captured significantly more “echogenic foci” than SIC (Chi²: p < 0.001). Artifacts (poor image quality, acoustic shadowing, sagittal incompletely displayed AFTN) were significantly more common on CL, affecting ~40% of AFTNs, compared to ~15% on SIC (Chi²: each p < 0.05). Weak correlation was observed for assessment confidence between CL and SIC, with SIC outperforming CL (Spearman’s correlation: each p < 0.001). Conclusions: A strong correlation was identified between CL and SIC in terms of RSS ratings and ACR FNC recommendations. Kwak is a superior representative of the benign character of AFTNs than ACR. However, CL provided more detailed information while being associated with decreased observer confidence and more artifacts. Specific operator training and technical improvements, including AI implementation, could improve image quality in future. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

24 pages, 334 KB

Open AccessEditor’s ChoiceReview

From Heart to Abdominal Aorta: Integrating Multi-Modal Cardiac Imaging Derived Haemodynamic Biomarkers for Abdominal Aortic Aneurysm Risk Stratification, Surveillance, Pre-Operative Assessment and Therapeutic Decision-Making

by Rafic Ramses and Obiekezie Agu

Diagnostics 2025, 15(19), 2497; https://doi.org/10.3390/diagnostics15192497 - 1 Oct 2025

Cited by 1 | Viewed by 1907

Abstract

Recent advances in cardiovascular imaging have revolutionized the assessment and management of abdominal aortic aneurysm (AAA) through the integration of sophisticated haemodynamic biomarkers. This comprehensive review evaluates the clinical utility and mechanistic significance of multiple biomarkers in AAA pathogenesis, progression, and treatment outcomes. [...] Read more.

Recent advances in cardiovascular imaging have revolutionized the assessment and management of abdominal aortic aneurysm (AAA) through the integration of sophisticated haemodynamic biomarkers. This comprehensive review evaluates the clinical utility and mechanistic significance of multiple biomarkers in AAA pathogenesis, progression, and treatment outcomes. Advanced cardiac imaging modalities, including four-dimensional magnetic resonance imaging (4D MRI), computational fluid dynamics (CFD), and specialized echocardiography, enable precise quantification of critical haemodynamic parameters. Wall shear stress (WSS) emerges as a fundamental biomarker, with values below 0.4 Pa indicating pathological conditions and increased risk for aneurysm progression. Time-averaged wall shear stress (TAWSS), typically maintaining values above 1.5 Pa in healthy arterial segments, provides crucial information about sustained haemodynamic forces affecting the vessel wall. The oscillatory shear index (OSI), ranging from 0 (unidirectional flow) to 0.5 (purely oscillatory flow), quantifies directional changes in WSS during cardiac cycles. In AAA, elevated OSI values between 0.3 and 0.4 correlate with disturbed flow patterns and accelerated disease progression. The relative residence time (RRT), combining TAWSS and OSI, identifies regions prone to thrombosis, with values exceeding 2–3 Pa⁻¹ indicating increased risk. The endothelial cell activation potential (ECAP), calculated as OSI/TAWSS, serves as an integrated metric for endothelial dysfunction risk, with values above 0.2–0.3 Pa⁻¹ suggesting increased inflammatory activity. Additional biomarkers include the volumetric perivascular characterization index (VPCI), which assesses vessel wall inflammation through perivascular tissue analysis, and pulse wave velocity (PWV), measuring arterial stiffness. Central aortic systolic pressure and the aortic augmentation index provide essential information about cardiovascular load and arterial compliance. Novel parameters such as particle residence time, flow stagnation, and recirculation zones offer detailed insights into local haemodynamics and potential complications. Implementation challenges include the need for specialized equipment, standardized protocols, and expertise in data interpretation. However, the potential for improved patient outcomes through more precise risk stratification and personalized treatment planning justifies continued development and validation of these advanced assessment tools. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: Innovations in Diagnosis and Management)

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI