Diagnostics

13 pages, 583 KB

Open AccessEditor’s ChoiceArticle

Transarterial Embolization for Malignancy-Related Gastrointestinal Bleeding: Outcomes with and Without CT Extravasation

by Kwang Kun Cho, Byung Chan Lee, Hyoung Ook Kim, Chan Park, In Woo Choi and John F. Angle

Diagnostics 2026, 16(15), 2350; https://doi.org/10.3390/diagnostics16152350 - 27 Jul 2026

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Background/Objectives: Gastrointestinal (GI) bleeding in patients with malignancy is frequently refractory to endoscopic and conservative management. Transarterial embolization (TAE) is an established treatment option, but whether the presence of contrast extravasation on preprocedural computed tomography (CT) influences outcomes remains unclear. This study [...] Read more.

Background/Objectives: Gastrointestinal (GI) bleeding in patients with malignancy is frequently refractory to endoscopic and conservative management. Transarterial embolization (TAE) is an established treatment option, but whether the presence of contrast extravasation on preprocedural computed tomography (CT) influences outcomes remains unclear. This study aimed to evaluate the efficacy and safety of TAE for malignancy-related GI bleeding in patients with and without CT-detected contrast extravasation. Methods: From January 2012 to December 2023, 40 consecutive patients who underwent TAE for malignancy-related GI bleeding were retrospectively analyzed and categorized into CT extravasation (n = 25) and CT no-extravasation (n = 15) groups based on preprocedural CT findings. Technical success, clinical success, 30-day mortality, overall survival (OS), and procedure-related complications were compared between groups, and factors associated with OS were evaluated using Cox regression. Results: The technical and clinical success rates were 100% (40/40) and 82.5% (33/40), respectively. Clinical success did not differ between the CT extravasation and no-extravasation groups (84.0% [21/25] vs. 80.0% [12/15]; p = 0.747). Two of 40 patients (5.0%) died within 30 days, one in each group (p = 0.708). OS did not differ significantly (log-rank p = 0.707; median, 147 vs. 187 days). A shock index > 1 was independently associated with worse OS (hazard ratio, 2.308; 95% confidence interval, 1.071–4.972; p = 0.033). No major procedure-related complications occurred. Conclusions: TAE achieved high technical success and comparable short-term clinical outcomes in patients with and without CT extravasation. Hemodynamic instability, rather than CT extravasation, was independently associated with OS. Full article

(This article belongs to the Special Issue Advancements in Interventional Radiology Techniques in Vascular and Extravascular Diseases)

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23 pages, 8113 KB

Open AccessEditor’s ChoiceArticle

Tomographic 3D Ultrasound for Thyroid Volumetry—A Comparison Between Multiplanar 2D and 3D Imaging Methods

by Robert Roth, Zoe Reinke, Martin Siedlecki, Jan Luitjens, Martin Hügle, Johanna S. Enke, Christian Liska, Laura-Marie Feitelson, Constantin Lapa, Thomas Kroencke, Robert Bauer and Thomas Wendler

Diagnostics 2026, 16(15), 2329; https://doi.org/10.3390/diagnostics16152329 - 25 Jul 2026

Viewed by 937

Abstract

Background: Accurate thyroid volume measurement is essential for diagnosing and monitoring thyroid disorders and for determining radioiodine therapy dosage. The ellipsoid method applied to two-dimensional B-mode ultrasound (Bmode-2D-US) is the most prevalent clinical approach, yet it is known to suffer from high observer [...] Read more.

Background: Accurate thyroid volume measurement is essential for diagnosing and monitoring thyroid disorders and for determining radioiodine therapy dosage. The ellipsoid method applied to two-dimensional B-mode ultrasound (Bmode-2D-US) is the most prevalent clinical approach, yet it is known to suffer from high observer dependence and limited accuracy. Tracked three-dimensional ultrasound (3D-US) is a promising radiation-free alternative, but direct comparisons across modalities under controlled conditions remain scarce. Methods: A custom-built anthropomorphic multi-modality phantom was constructed containing six anatomically realistic thyroid lobe samples molded from segmented MRI data, with ground truth volumes verified by the suspension method and 3D surface scanning. Volume measurements were performed by six observers of varying experience using Bmode-2D-US, electromagnetically tracked 3D-US (EM-3D-US), inertial-measurement-unit-tracked 3D-US (IMU-3D-US), and optically tracked 3D-US (Opt-3D-US), as well as computed tomography (CT) and magnetic resonance imaging (MRI). Inter- and intraobserver variability were assessed using modified Bland–Altman analysis. Results: All three 3D-US methods reduced inter- and intraobserver variability compared to Bmode-2D-US, achieving variability comparable to CT and lower than MRI. Mean accuracy was similar across 3D-US, CT, and MRI. Bmode-2D-US showed strong observer dependence, with operator experience having the most pronounced effect on this method. Among tracked methods, EM-3D-US and Opt-3D-US were least sensitive to operator movement quality, while IMU-3D-US showed somewhat higher sensitivity. Conclusions: Tracked 3D-US is a promising radiation-free alternative to conventional Bmode-2D-US for thyroid volumetry, offering improved reproducibility and accuracy across operators of varying experience in this phantom-based evaluation. Full article

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

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26 pages, 2516 KB

Open AccessEditor’s ChoiceArticle

Enhancing PET/CT Radiomics Robustness Through Graph Signal Processing

by Tommaso Latino, Alessandro Stefano, Giovanni Pasini, Franco Marinozzi, Giorgio Russo and Fabiano Bini

Diagnostics 2026, 16(14), 2284; https://doi.org/10.3390/diagnostics16142284 - 21 Jul 2026

Viewed by 451

Abstract

Background/Objectives: Prostate cancer (PCa) frequently metastasizes to bone, leading to severe clinical complications and reduced quality of life. Accurate and robust imaging-based characterization of bone lesions is therefore critical for diagnosis and treatment planning. Radiomics has emerged as a powerful tool for [...] Read more.

Background/Objectives: Prostate cancer (PCa) frequently metastasizes to bone, leading to severe clinical complications and reduced quality of life. Accurate and robust imaging-based characterization of bone lesions is therefore critical for diagnosis and treatment planning. Radiomics has emerged as a powerful tool for extracting quantitative information from medical images; however, classical radiomics features are often affected by inter-scanner variability, segmentation dependence, and limited ability to describe lesions with complex biological heterogeneity. This study aims to introduce a translational graph-based radiomics approach designed to extract novel quantitative descriptors with improved robustness and clinical reliability. Methods: A graph representation was derived from segmented Positron Emission Tomography/Computed Tomography (PET/CT) bone lesions by generating a point cloud followed by Delaunay triangulation to preserve geometric information. Graph signal processing techniques were applied to extract three classes of features: orientation, connectivity, and transform-based descriptors. The dataset included PET/CT scans from 50 PCa patients acquired using two different scanners, comprising 92 bone lesions classified as benign or malignant. Correlation analysis with classical radiomics features was performed to assess information redundancy. Robustness against batch effects and segmentation variability was evaluated. Classification performance was tested using Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) models based on proposed features, classical features, and their combination. Results: The proposed features captured non-redundant information compared to classical radiomics and demonstrated superior robustness to scanner-related batch effects and segmentation variability. In classification tasks, models using the proposed features consistently outperformed those based on classical radiomics. Using LDA, the proposed features achieved a mean balanced accuracy of 69.68% and a mean Area Under the Curve (AUC) of 72.14%. With SVM, they achieved a mean balanced accuracy of 65.16% and a mean AUC of 66.49%, exceeding the performance of classical and combined feature sets. Conclusions: This study presents a translational graph-based radiomics framework that extends beyond conventional methodologies, improving robustness and diagnostic performance. The proposed approach shows promise as an integrative tool for more reliable PET/CT-based characterization of bone lesions in prostate cancer. Full article

(This article belongs to the Special Issue Artificial Intelligence for Health and Medicine—2nd Edition)

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13 pages, 963 KB

Open AccessEditor’s ChoiceReview

Choline PET/CT in the PSMA Era: Clinical Repositioning, Biological Perspectives, and Emerging Applications

by Virginia Rossetti, Lorenzo Fantini, Irene Marini, Monica Celli, Ilaria Grassi, Maddalena Sansovini, Silvia Nicolini, Federica Matteucci and Paola Caroli

Diagnostics 2026, 16(13), 2108; https://doi.org/10.3390/diagnostics16132108 - 6 Jul 2026

Viewed by 516

Abstract

The widespread adoption of prostate-specific membrane antigen (PSMA)-targeted PET/CT has profoundly reshaped molecular imaging in prostate cancer and has substantially reduced the routine use of radiolabeled choline tracers. However, the transition from choline to PSMA imaging should not be interpreted simply as the [...] Read more.

The widespread adoption of prostate-specific membrane antigen (PSMA)-targeted PET/CT has profoundly reshaped molecular imaging in prostate cancer and has substantially reduced the routine use of radiolabeled choline tracers. However, the transition from choline to PSMA imaging should not be interpreted simply as the replacement of one radiopharmaceutical by another, but rather as part of a broader evolution from metabolism-based imaging toward receptor-targeted and biology-driven imaging strategies. This narrative review critically reassesses the residual and emerging role of choline PET/CT in the PSMA era, with particular attention to the biological rationale of choline uptake, selected prostate cancer scenarios, and extra-prostatic applications. In prostate cancer, PSMA PET/CT remains the dominant imaging modality because of its superior diagnostic performance, particularly in biochemical recurrence; nevertheless, choline PET/CT may provide complementary metabolic information in highly selected settings, including PSMA-low or heterogeneous disease, aggressive or dedifferentiated variants, neuroendocrine transformation, equivocal PSMA findings, and limited PSMA availability. These prostate cancer applications, however, are supported mainly by biological rationale, indirect evidence, and limited clinical data and should therefore be regarded as exploratory rather than established indications. By contrast, ¹⁸F-fluorocholine PET/CT has emerged as a clinically established imaging modality in primary hyperparathyroidism, particularly after negative or inconclusive conventional imaging, with prospective studies and meta-analyses demonstrating high detection rates and superior performance compared with conventional scintigraphic techniques. Additional applications in hepatocellular carcinoma and selected neuro-oncologic settings remain exploratory and require further validation. Overall, choline PET/CT should not be considered obsolete in the PSMA era, but selectively repositioned within biology-driven and multiparametric imaging strategies, with its strongest evidence currently supporting primary hyperparathyroidism and its other applications requiring cautious interpretation and further prospective validation. Full article

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

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18 pages, 14328 KB

Open AccessEditor’s ChoiceArticle

Diagnostic Significance of Ki-67, p53, and Mucin Glycoprotein Expression in Colorectal Serrated Lesions: Further Immunohistochemical Studies

by Ivan Ilić, Pavle Ranđelović, Ilija Golubović, Milan Lazarević, Maja Jovičić Milentijević, Biljana Radovanović Dinić, Ivana Đorđević, Jana Cvetković and Milica Veljković

Diagnostics 2026, 16(13), 2099; https://doi.org/10.3390/diagnostics16132099 - 4 Jul 2026

Viewed by 428

Abstract

Background/Objectives: Colorectal serrated lesions are highly heterogeneous at the micromorphological level. Their morphology can range from seemingly harmless, as in the case of hyperplastic polyps with little to no neoplastic potential, to lesions that can undergo malignant transformation within a short period of [...] Read more.

Background/Objectives: Colorectal serrated lesions are highly heterogeneous at the micromorphological level. Their morphology can range from seemingly harmless, as in the case of hyperplastic polyps with little to no neoplastic potential, to lesions that can undergo malignant transformation within a short period of time. The serrated morphology of these lesions is primarily a consequence of morphological changes resulting from the enlargement and budding of the adenoma, as well as the migration of its epithelium at the crypt level. This creates elevations that resemble saw teeth. In this study, the serrated morphology was highlighted immunohistochemically using the MUC2 marker. Results: MUC5AC immunohistochemical expression exhibited greater variability in positivity and intensity compared to MUC2 expression. Pancryptic MUC5AC positivity was present in 75% of TSA cases and in 75% of malignantly transformed serrated lesions. This correlates with advanced histologic lesions and dysplasia development within the serrated pathway of carcinogenesis. MUC5AC is a useful marker for detecting polyps undergoing malignant transformation but not for distinguishing between sessile serrated lesions and hyperplastic polyps. Analysis of Ki-67 proliferative activity in serrated lesions in this study showed that a shift in the proliferative zone along the entire crypt was statistically significant only in TSA (p < 0.01). p53 expression increases from low-grade to high-grade dysplasia and malignant transformation of serrated lesions. This study confirmed that p53 expression in the upper half of the crypt was present in 11% of sessile serrated lesions without dysplasia and in 18% with dysplasia. In malignantly transformed serrated lesions, pancryptic positivity was present in 25% of cases. Conclusions: A marker panel consisting of mucin glycoproteins, Ki-67, and p53 could be useful in assessing the risk level of malignant transformation in serrated lesions. Full article

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

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24 pages, 2010 KB

Open AccessEditor’s ChoiceArticle

Do Fasting GLP-1 and GIP Levels Predict the Initial Pharmacological Response to Semaglutide and Tirzepatide?

by Sandro La Vignera, Cristian Fioriglio and Rosita A. Condorelli

Diagnostics 2026, 16(13), 1979; https://doi.org/10.3390/diagnostics16131979 - 25 Jun 2026

Viewed by 2445

Abstract

Background/Objectives: Semaglutide and tirzepatide demonstrate substantial efficacy in obesity treatment, yet individual responses vary markedly. The incretin system—comprising glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—is frequently dysregulated in obesity, but whether fasting incretin levels predict differential pharmacological responses remains unexplored. We [...] Read more.

Background/Objectives: Semaglutide and tirzepatide demonstrate substantial efficacy in obesity treatment, yet individual responses vary markedly. The incretin system—comprising glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—is frequently dysregulated in obesity, but whether fasting incretin levels predict differential pharmacological responses remains unexplored. We investigated whether combinatorial fasting GLP-1/GIP tertile profiles predict the initial weight-loss response to semaglutide versus tirzepatide in patients with severe obesity. Methods: This prospective, parallel-group, open-label pilot study enrolled 90 treatment-naïve patients with BMI > 40 kg/m² (mean 42.5 ± 3.5 kg/m²) at the University of Catania, Italy. Fasting serum GLP-1 (0.8–50 pg/mL) and GIP (1–16 ng/mL) were measured by chemiluminescence immunoassay and distributed into tertiles, generating nine combinatorial profiles (P1–P9; n = 10 per profile). Within each profile, five patients were randomly assigned to semaglutide (escalated to 2.4 mg/week) or tirzepatide (escalated to 15 mg/week). Primary outcome was pharmacological response category at six months: low (<5% body weight reduction), intermediate (5–15%), or optimal (>15%). Results: Baseline characteristics were balanced across profiles (age 48 ± 8 years, BMI 42.5 ± 3.5 kg/m², waist circumference 134 ± 12 cm, HOMA-IR 8.5 ± 3.0; all p > 0.05). Tirzepatide achieved optimal response in profiles with low GIP tertile regardless of GLP-1 level (P1, P6, P8), while semaglutide achieved optimal response when GLP-1 was low and GIP was intermediate-to-high (P4, P5). Both drugs showed low response in the high GLP-1/high GIP profile (P3). Mean weight loss in optimal-response groups was 18.2 ± 2.1% for tirzepatide and 16.8 ± 1.9% for semaglutide. Waist circumference reductions paralleled weight loss patterns. HOMA-IR decreased significantly in all optimal-response groups (mean reduction 4.2 ± 1.1 units). Conclusions: In this hypothesis-generating pilot study, fasting GLP-1/GIP combinatorial profiling, obtained from a single fasting blood sample, was associated with differential pharmacological responses to semaglutide and tirzepatide in severe obesity. Low GIP levels were tentatively associated with optimal tirzepatide response; low GLP-1 with intermediate-to-high GIP was tentatively associated with optimal semaglutide response. These preliminary findings provide proof-of-concept for incretin-guided personalised obesity pharmacotherapy but require confirmation in larger, adequately powered randomised trials before any clinical recommendations can be made. The inability to discriminate incretin secretory deficiency from receptor resistance using fasting measurements alone, the absence of a placebo control, and the six-month follow-up (shorter than the 12–18 months at which maximal efficacy is typically observed) remain critical limitations. Full article

(This article belongs to the Special Issue Clinical and Biochemical Diagnosis and Management of Obesity)

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17 pages, 2302 KB

Open AccessEditor’s ChoiceReview

Early Rectal Cancer: Diagnostic Challenges and the Role of Endoscopic Intermuscular Dissection Within the Therapeutic Algorithm

by Rossella Maresca, Giulio Calabrese, Franziska Deutschbein, Valentina Blasi, Tommaso Schepis, Daniele Salvi, Silvia Pecere, Paola Cesaro, Cristiano Spada, Sandro Sferrazza and Federico Barbaro

Diagnostics 2026, 16(12), 1936; https://doi.org/10.3390/diagnostics16121936 - 22 Jun 2026

Viewed by 1854

Abstract

Early rectal cancer represents a challenging setting in which accurate locoregional staging is essential to guide appropriate treatment. Current diagnostic strategies primarily include magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, both modalities show significant limitations in early-stage disease, particularly in T [...] Read more.

Early rectal cancer represents a challenging setting in which accurate locoregional staging is essential to guide appropriate treatment. Current diagnostic strategies primarily include magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, both modalities show significant limitations in early-stage disease, particularly in T staging. This diagnostic gap impacts therapeutic decision-making, particularly in patients with lesions suggestive of deep submucosal invasion. In these cases, endoscopic submucosal dissection (ESD) may be insufficient to achieve adequate vertical negative margins, whereas radical surgery is associated with considerable morbidity and potential impairment of quality of life. In this gray zone, endoscopic intermuscular dissection (EID) has recently emerged as a novel therapeutic approach designed to overcome the limitations of standard endoscopic resection. By enabling dissection within the deeper intermuscular plane, it can achieve curative resections while preserving rectal wall integrity. This narrative review aims to explore the current diagnostic gaps in early rectal cancer and to define the potential role of EID within the current therapeutic algorithm. Full article

(This article belongs to the Special Issue Advances in Gastrointestinal Endoscopy: From Diagnosis to Therapy)

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13 pages, 14564 KB

Open AccessEditor’s ChoiceArticle

Shape-Sensing Robotic Bronchoscopy with Integrated Mobile Cone-Beam CT Guidance for Intraoperative Localization of Lung Tumors Using Indocyanine Green

by Abdul Rahman Halawa, Miguel Belmonte, Kyle G. Mitchell, Mara B. Antonoff, Ravi Rajaram, Stephen Swisher, David C. Rice and Roberto F. Casal

Diagnostics 2026, 16(12), 1893; https://doi.org/10.3390/diagnostics16121893 - 18 Jun 2026

Viewed by 1966

Abstract

Background/Objectives: With increasing frequency in sublobar resections, accurate intraoperative localization has become essential to ensure adequate resection margins and spare lung parenchyma. Our study evaluates the efficacy of shape-sensing robotic bronchoscopy (SS-RAB) with integrated mobile cone-beam CT (mCBCT) for intraoperative localization of lung [...] Read more.

Background/Objectives: With increasing frequency in sublobar resections, accurate intraoperative localization has become essential to ensure adequate resection margins and spare lung parenchyma. Our study evaluates the efficacy of shape-sensing robotic bronchoscopy (SS-RAB) with integrated mobile cone-beam CT (mCBCT) for intraoperative localization of lung tumors using indocyanine green (ICG). We further aimed to explore the feasibility of a single intubation-single positioning technique for bronchoscopy and surgery. Methods: We retrospectively reviewed patients who underwent SS-RAB with integrated mCBCT for ICG marking, followed by minimally invasive sublobar resection. ICG marking was deemed successful when it allowed the operative team to localize and resect the lesion with adequate pathology margins. Results: A total of 28 patients with 30 pulmonary lesions from a single institution were included. Median tumor size was 10.5 mm (IQR, 8.7–14.6 mm) and distance from pleura 7.8 mm (IQR, 2.45–13.8 mm). Twenty lesions (66.6%) were solid, 5 lesions (16.6%) semi-solid, and 5 lesions (16.6%) ground-glass. ICG localization was successful in 28 lesions (93%). Nineteen patients (68%) were intubated only with a double-lumen endotracheal tube (DL-ETT), used for bronchoscopy and surgery, and in 10 patients (36%) ICG marking and surgery were both performed in lateral decubitus. One patient developed a small pneumothorax during bronchoscopy which did not prevent ICG injection. Conclusions: SS-RAB with integrated mCBCT for ICG marking is successful and safe. Single intubation with DL-ETT and lateral decubitus positioning for both bronchoscopy and surgery are feasible. Further studies are needed to prove a potential increase in efficiency with this technique. Full article

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

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17 pages, 1555 KB

Open AccessEditor’s ChoiceReview

Whole-Body Dynamic Positron Emission and Computed Tomography (WBD-PET/CT): Latest Developments, Challenges and Opportunities

by Anastasios Vatalis, Dimitra Tsivaka, Varvara Valotassiou, Emmanouil Panagiotidis, Panagiotis Georgoulias, Nicolas A. Karakatsanis and Ioannis Tsougos

Diagnostics 2026, 16(12), 1866; https://doi.org/10.3390/diagnostics16121866 - 16 Jun 2026

Viewed by 1821

Abstract

Whole-body dynamic positron emission tomography/computed tomography (WBD-PET/CT) has transformed medical imaging, enabling the fusion between (i) detailed anatomical maps of the human body and (ii) quantitative multi-parametric functional maps of specific biochemical and physiological processes across the human body beyond the semi-quantitative limitations [...] Read more.

Whole-body dynamic positron emission tomography/computed tomography (WBD-PET/CT) has transformed medical imaging, enabling the fusion between (i) detailed anatomical maps of the human body and (ii) quantitative multi-parametric functional maps of specific biochemical and physiological processes across the human body beyond the semi-quantitative limitations of static PET/CT imaging. Latest developments in systems hardware, particularly with the introduction of long-axial-field-of-view (LAFOV) and Time-of-Flight (TOF) PET scanners and low-dose CT scanners, and in data analysis, primarily with direct parametric PET image reconstruction and Artificial Intelligence, offer unprecedented opportunities towards the wide clinical adoption of the superior quantitative accuracy and precision of WBD-PET/CT imaging overcoming current challenges, such as data acquisition complexity and long scan durations. This review aims to summarize the latest developments, current challenges, and emerging opportunities in WBD-PET/CT, emphasizing its potential to broaden the diagnostic and theranostic role of PET/CT in clinical practice. Full article

(This article belongs to the Special Issue Whole-Body PET/CT: From Diagnosis to Prognosis)

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16 pages, 5936 KB

Open AccessEditor’s ChoiceArticle

A National Audit of Mammography Systems Settings That May Affect the Output of Artificial Intelligence Software

by Alistair Mackenzie, John Loveland, Leila Farshadi, Carlijn Roozemond and Ruben E. van Engen

Diagnostics 2026, 16(12), 1842; https://doi.org/10.3390/diagnostics16121842 - 14 Jun 2026

Cited by 1 | Viewed by 953

Abstract

Background: Artificial Intelligence (AI) software in mammography is trained on a set of processed images and may be less effective when applied to images acquired on different systems or systems with different processing and/or acquisition settings. The aim of this work was to [...] Read more.

Background: Artificial Intelligence (AI) software in mammography is trained on a set of processed images and may be less effective when applied to images acquired on different systems or systems with different processing and/or acquisition settings. The aim of this work was to undertake a retrospective audit of a large number of mammography systems in the United Kingdom and identify the number of differences in image acquisition and processing factors. Methods: Images of the TORMAM phantom are acquired as part of the routine quality control programme. Data from the DICOM header of these images were extracted to provide a snapshot in time of the system configurations. A longitudinal audit of DICOM header data for all of the Hologic systems was tested by one medical physics department (MPD1) over 14 years. Results: We received results from 28 UK medical physics services for 498 systems. There were 7 different models of mammography systems, each with up to 7 different versions of acquisition workstation software. Each mammographic model had multiple image processing versions, including bespoke settings. The GE had two dose settings, while Siemens systems had a range of doses from 80% to 150% of the standard dose. In the longitudinal audit, there were between 2 and 6 software versions in concurrent use on the Hologic systems tested by MPD1. Conclusions: This study showed the heterogeneity of system setup across the UK in a single year, as well as changes to system setup over time. These differences may affect the outcomes of both AI and human readers. There are responsibilities on AI suppliers, mammography equipment manufacturers, breast-screening units, and medical physics services to ensure outcomes are not adversely affected by differences or changes in mammography equipment configurations. Full article

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

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37 pages, 3405 KB

Open AccessEditor’s ChoiceArticle

Hypoxia Associated Integration of Epigenetic, Metabolic, and Immune Biomarkers in Blood and Urine for Early Colorectal Cancer Detection: A Multimarker Panel

by Christopher Birigwa, Bing Qu, Yongqing Tong, Teng Zuo, Wenzheng Yuan, Qingbo Wang, Wei Song, Weiwei Wan, Jing Xiong, Jianfei Luo and Qiang Tong

Diagnostics 2026, 16(12), 1753; https://doi.org/10.3390/diagnostics16121753 - 6 Jun 2026

Cited by 1 | Viewed by 758

Abstract

Background: Detection of colorectal cancer (CRC) currently relies mainly on invasive procedures such as colonoscopy. In experimental models, tumor hypoxia induces epigenetic, metabolic, and immune changes via hypoxia-inducible factor (HIF) signaling. Building on these published insights, this study evaluated whether a panel of [...] Read more.

Background: Detection of colorectal cancer (CRC) currently relies mainly on invasive procedures such as colonoscopy. In experimental models, tumor hypoxia induces epigenetic, metabolic, and immune changes via hypoxia-inducible factor (HIF) signaling. Building on these published insights, this study evaluated whether a panel of biomarkers previously associated with hypoxia-related processes, plasma methylated SEPT9 (mSEPT9), urinary N¹, N¹²-diacetylspermine (DiAcSpm), and systemic inflammatory indices (NLR, PLR, and LMR)—could be combined into a non-invasive diagnostic panel and compared with standard serum tumor markers. This study focused solely on diagnostic performance; it did not directly assess tumor hypoxia or HIF expression in patients. This study was conducted in a clinical diagnostic setting (patients with confirmed CRC, polyps, or benign surgical conditions) and does not represent a population-based screening cohort. Limitations include the lack of an external validation cohort; all analyses were performed on a single dataset, and the reported performance metrics may be optimistic. Independent validation is required before clinical implementation. Methods: This prospective single-center study enrolled 382 participants: 142 with CRC, 62 with colorectal polyps, and 178 non-malignant controls. Plasma mSEPT9 was quantified by real-time PCR, urinary DiAcSpm by ELISA, and inflammatory indices from blood counts. Serum tumor markers (CEA, CA19-9, CA125, and AFP) were measured by immunoassay. Diagnostic accuracy was assessed using ROC analysis and multivariable logistic regression. Results: mSEPT9 (AUC 0.843) and DiAcSpm (AUC 0.831) demonstrated significantly higher diagnostic accuracy than CEA (AUC 0.660) and CA19-9 (AUC 0.649). A combined panel including mSEPT9, DiAcSpm, NLR, PLR, and LMR achieved an AUC of 0.947, with 85.9% sensitivity and 92.9% specificity. This panel also showed strong performance for early-stage CRC (AUC 0.905). Conclusions: A multimarker panel of biomarkers (mSEPT9, DiAcSpm, NLR, PLR, and LMR) provides a non-invasive diagnostic approach for CRC detection in a clinical case–control setting. Validation in asymptomatic screening populations is required before any screening claim can be made. These findings are associative; direct evidence that tumor hypoxia drives these biomarker changes was not obtained and requires future investigation. Full article

(This article belongs to the Special Issue Advancements in Diagnosis of Colorectal Cancer)

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32 pages, 25206 KB

Open AccessEditor’s ChoiceArticle

TransNet–SAM2: A Transformer–Foundation Model Framework for Prompt-Free Segmentation of White Blood Cells in Microscopic Blood Smear Images

by Julius Bamwenda, Mehmet Siraç Özerdem, Orhan Ayyildiz, Veysi Akpolat and İrem Akpolat

Diagnostics 2026, 16(11), 1737; https://doi.org/10.3390/diagnostics16111737 - 4 Jun 2026

Cited by 1 | Viewed by 693

Abstract

Background: Accurate segmentation of white blood cells (WBCs) in peripheral blood smear images is a fundamental step in computational hematology, enabling downstream tasks such as classification, morphological assessment, and quantitative analysis. However, reliable segmentation remains challenging due to staining variability, complex cellular [...] Read more.

Background: Accurate segmentation of white blood cells (WBCs) in peripheral blood smear images is a fundamental step in computational hematology, enabling downstream tasks such as classification, morphological assessment, and quantitative analysis. However, reliable segmentation remains challenging due to staining variability, complex cellular morphology, overlapping structures, and limited availability of high-quality annotations. Aim and Methods: The aim of this study is to develop a robust and fully automated segmentation framework for white blood cells (WBCs) in microscopic blood smear images, providing a reliable foundation for subsequent computational analysis. We propose TransNet–SAM2, a hybrid deep learning architecture that integrates hierarchical transformer-based feature extraction with a foundation-model-based decoder for prompt-free segmentation. Specifically, a Swin Transformer backbone is employed to capture multi-scale contextual representations, which are subsequently aligned and fused through a feature adaptation module. The fused features are directly injected into the SAM2 mask decoder, replacing conventional prompt-based conditioning and enabling fully automatic segmentation. In addition, a weakly supervised self-training strategy is incorporated to utilize partially annotated data, improving model generalization while reducing annotation requirements. The proposed framework is evaluated using a clinically curated dataset from Dicle University, the publicly available Raabin-WBC dataset, and an additional external leukemic blast validation dataset (ALL-IDB) to assess robustness under both routine and atypical hematological conditions. Results: TransNet-SAM2 achieved a Dice coefficient of 0.95 ± 0.01 and IoU of 0.90 on internal testing, significantly outperforming U-Net (0.89), Mask R-CNN (0.90), and SAM2 (0.92) (p < 0.05). In cross-dataset evaluation (Dicle training, Raabin-WBC testing), the framework maintained strong performance (Dice: 0.91, IoU: 0.84), demonstrating robustness to domain shifts. Ablation studies confirmed each component’s contribution, with the full model improving Dice by 6% over a CNN baseline. Qualitative analysis showed accurate boundary delineation even with cell overlap and background clutter. Conclusions: These findings indicate that the proposed framework provides a promising and scalable framework for WBC segmentation. While the current study focuses on segmentation, future work will investigate integration with classification and radiomics pipelines, as well as validation on more diverse clinical datasets, including bone marrow and leukemia samples. Full article

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

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19 pages, 1336 KB

Open AccessEditor’s ChoiceArticle

Explainable Boosting Machine in Sepsis Prediction Using Platelet Metabolomics: An Interpretable Machine Learning Approach

by Emek Guldogan, Burak Yagin, Yavuz Korkmaz, Sarah A. Alzakari, Amal K. Alkhalifa, Fahaid Al-Hashem and Fatma Hilal Yagin

Diagnostics 2026, 16(11), 1643; https://doi.org/10.3390/diagnostics16111643 - 27 May 2026

Viewed by 636

Abstract

Background: Sepsis remains a leading cause of mortality in emergency and intensive care settings, with early diagnosis representing a critical determinant of patient outcomes. Despite advances in biomarker discovery, integrating platelet-derived metabolic signatures with explainable machine learning frameworks for sepsis prediction remains underexplored. [...] Read more.

Background: Sepsis remains a leading cause of mortality in emergency and intensive care settings, with early diagnosis representing a critical determinant of patient outcomes. Despite advances in biomarker discovery, integrating platelet-derived metabolic signatures with explainable machine learning frameworks for sepsis prediction remains underexplored. The clinical adoption of predictive models has been hindered by the “black box” nature of conventional algorithms, limiting clinician trust and understanding. Objective: This study aimed to evaluate and validate an interpretable machine learning model utilizing platelet metabolomics data for accurate sepsis prediction while providing clinically meaningful explanations of the underlying metabolic disturbances that could inform therapeutic decision-making. Methods: We analyzed metabolomics data, comprising 25 sepsis patients diagnosed according to Sepsis-3 criteria and 14 age- and gender-matched non-sepsis from the emergency department. Platelet metabolite profiles were obtained via quantitative ¹H-NMR spectroscopy. Five machine learning algorithms were evaluated: Explainable Boosting Machine (EBM), Support Vector Machine (SVM), Logistic Regression (LR), Gradient Boosting Machine (GBM), and AdaBoost. Three biologically motivated metabolite ratios (adenosine triphosphate/adenosine diphosphate (ATP/ADP), ATP/adenosine monophosphate (AMP), Glutamine/Glutamate) were derived as additional features, yielding 22 candidate variables. Models were evaluated using a fully nested leave-one-out cross-validation (LOOCV) framework in which log transformation, KNN imputation, BorderlineSMOTE class balancing, and hyperparameter optimisation were performed exclusively within each training fold. Global and local interpretability analyses were performed to identify discriminative metabolites. Results: EBM achieved the highest ROC-AUC (0.864; 95% CI: 0.736–1.000), the highest PR-AUC (0.902; 95% CI: 0.783–0.997), and the best Brier score (0.189; 95% CI: 0.130–0.258) among all evaluated models, with sensitivity 0.880 (95% CI: 0.640–1.000; TP = 22/25) and specificity 0.714 (95% CI: 0.357–1.000; TN = 10/14). Global feature importance identified Carnitine, myo-Inositol, ADP, and O-Phosphoethanolamine as the leading single-feature predictors, alongside three pairwise interaction terms reflecting non-additive energy–amino acid metabolic relationships. Local explanations demonstrated that the ADP–Creatine interaction, Glutamine, and myo-Inositol drove correct sepsis classification in a representative true positive case. Conclusions: The EBM model demonstrated the highest discriminative performance and best calibration among all evaluated models, providing transparent mechanistic insights through global feature importance, and patient-level local explanations. These findings position the proposed framework as a proof-of-concept warranting external validation in larger, multi-centre cohorts before any clinical application is considered. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence to Advance Individualized Diagnosis and Treatment in Emergency and Critical Care Medicine, 2nd Edition)

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16 pages, 1157 KB

Open AccessEditor’s ChoiceArticle

A Combined Serum Biomarker Panel for Early Prediction of Response to Anti-TNF Therapy in Rheumatoid Arthritis: Toward a Precision Medicine Approach

by Bogdan Ion Gavrila, Claudia Ciofu and Marilena Stoian

Diagnostics 2026, 16(11), 1627; https://doi.org/10.3390/diagnostics16111627 - 26 May 2026

Viewed by 844

Abstract

Background/Objectives: Response to TNF inhibitors in RA remains heterogeneous and reliable predictors of treatment response are still lacking. Biomarker-based stratification may improve therapeutic decision-making and aligns with the emerging paradigm of precision medicine. Methods: We conducted a prospective observational study including 64 biologic-naïve [...] Read more.

Background/Objectives: Response to TNF inhibitors in RA remains heterogeneous and reliable predictors of treatment response are still lacking. Biomarker-based stratification may improve therapeutic decision-making and aligns with the emerging paradigm of precision medicine. Methods: We conducted a prospective observational study including 64 biologic-naïve patients with active RA being inadequately controlled by csDMARDs. All patients initiated anti-TNF therapy and were followed for 12 months. Clinical response was assessed at 6 and 12 months using EULAR response criteria based on DAS28-CRP. Baseline serum levels of classical biomarkers (RF type IgM, RF type IgA, anti-CCP) and additional biomarkers (anti-MCV,14-3-3η protein, COMP) were evaluated. Logistic regression analyses were performed to identify predictors of treatment response. Results: At 6 months, 7 patients were classified as non-responders, 38 as moderate responders, and 19 as good responders Lower baseline levels of RF isotypes, anti-CCP antibodies, 14-3-3η protein, and COMP were associated with favorable clinical response at 6 months. Baseline anti-CCP and 14-3-3η protein levels emerged as significant predictors in univariate analysis. Multivariate logistic regression yielded a predictive model incorporating anti-CCP, 14-3-3η protein, and COMP, achieving an overall prediction accuracy of 89.1%. At 12 months, baseline RF isotypes remained associated with treatment response, whereas the predictive value of other biomarkers diminished. Longitudinal analysis demonstrated significant reductions mainly for classical autoantibody levels under anti-TNF α inhibitors. Conclusions: A combined serum biomarker panel may support early prediction of response to anti-TNF therapy in RA. These findings highlight the potential of integrated biomarker-based stratification to optimize therapeutic decisions and support the implementation of precision medicine approaches in RA. Full article

(This article belongs to the Special Issue Current Perspectives and Gaps in the Diagnosis and Management of Rheumatic Diseases)

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32 pages, 2959 KB

Open AccessEditor’s ChoiceReview

When Immunophenotype Is Not Identity: A Clinicopathological Review of Neuroendocrine Differentiation in Tumors of the Female Genital Tract

by Catalin-Bogdan Satala, Alina-Mihaela Gurau, Gabriela Patrichi, Roxana-Cristina Mehedinti, Andy Radu Leibovici and Gabriela Gurau

Diagnostics 2026, 16(10), 1573; https://doi.org/10.3390/diagnostics16101573 - 21 May 2026

Cited by 1 | Viewed by 670

Abstract

Neuroendocrine differentiation in tumors of the female genital tract is an uncommon but diagnostically consequential finding. Its interpretation is challenging because neuroendocrine marker expression does not necessarily define a neuroendocrine neoplasm. Focal or aberrant staining for synaptophysin, chromogranin A, CD56 or INSM1 may [...] Read more.

Neuroendocrine differentiation in tumors of the female genital tract is an uncommon but diagnostically consequential finding. Its interpretation is challenging because neuroendocrine marker expression does not necessarily define a neuroendocrine neoplasm. Focal or aberrant staining for synaptophysin, chromogranin A, CD56 or INSM1 may occur in otherwise conventional gynecologic carcinomas, whereas true poorly differentiated neuroendocrine carcinomas represent aggressive tumors with distinct prognostic and therapeutic implications. This narrative review examines neuroendocrine differentiation across the cervix, endometrium, ovary, vagina and vulva from an integrated clinicopathologic perspective. We emphasize that neuroendocrine differentiation should be approached as a diagnostic and biological spectrum, ranging from incidental immunophenotypic expression to carcinoma with neuroendocrine differentiation, mixed neuroendocrine/non-neuroendocrine tumors, well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Morphology remains the diagnostic anchor, while immunohistochemistry, molecular context and clinicoradiologic correlation refine classification and help exclude mimics or metastatic disease. Site-specific interpretation is essential: cervical neuroendocrine carcinoma is commonly HPV-associated and clinically aggressive; endometrial tumors require integration with p53, mismatch repair, POLE and SWI/SNF-related contexts; ovarian lesions demand distinction between primary well-differentiated neuroendocrine tumors, poorly differentiated carcinomas and metastases; and vaginal or vulvar tumors require careful exclusion of adjacent extension, cutaneous mimics and extragenital primaries. We propose a practical diagnostic framework that separates incidental marker expression from clinically meaningful neuroendocrine differentiation and links this distinction to reporting, prognosis and treatment. The central diagnostic question is not whether neuroendocrine markers are expressed but whether their expression defines a morphologically, biologically and clinically meaningful tumor category. Full article

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

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20 pages, 4148 KB

Open AccessEditor’s ChoiceArticle

Intraoperative Multimodal Bowel Perfusion Quantification Combining Hyperspectral Imaging and Indocyanine Green

by Georg Thiele, Annekatrin Pfahl, Hannes Köhler, Matthias Mehdorn, Sigmar Stelzner, Ines Gockel, Andreas Melzer and Boris Jansen-Winkeln

Diagnostics 2026, 16(10), 1568; https://doi.org/10.3390/diagnostics16101568 - 21 May 2026

Viewed by 589

Abstract

Background/Objectives: Intraoperative perfusion imaging can support determining the anastomosis site to avoid leakages after colorectal surgery. Indocyanine green–fluorescence angiography (ICG-FA) and hyperspectral imaging (HSI) have been used recently but suffering from different drawbacks. A comparison of quantitative perfusion parameters from both modalities should [...] Read more.

Background/Objectives: Intraoperative perfusion imaging can support determining the anastomosis site to avoid leakages after colorectal surgery. Indocyanine green–fluorescence angiography (ICG-FA) and hyperspectral imaging (HSI) have been used recently but suffering from different drawbacks. A comparison of quantitative perfusion parameters from both modalities should substantiate the relevance of HSI next to ICG-FA. A computational framework combining ICG-FA and HSI should be developed to overcome system-specific disadvantages. Methods: ICG-FA and HSI were performed in 26 non-consecutive patients undergoing any colorectal surgery at the University Hospital of Leipzig between November 2022 and December 2023 to compare the position of the transition between well- and poorly perfused areas in both imaging modalities, as well as to compare quantitative perfusion parameters. Hyperspectral data was acquired before, during, and after ICG-FA to reconstruct an ICG-mimicking image from HSI data for future combined applications. This approach was further tested by investigating the influence of ICG on HSI-derived tissue parameters. Results: Anastomotic leakage occurred in one case. Compared to the clinical assessment, the median position of the transection margin was 0.1 cm more proximal, 0.15 cm more proximal, and 0.36 cm more distal for ICG, reconstructed ICG, and HSI, respectively. The reconstructed ICG image resembled the ground truth in 21 cases. ICG did not show any relevant influence on HSI parameters. Conclusions: The results indicated subtle differences between ICG-based blood flow and HSI-derived tissue oxygenation visualisation, which can be combined for comprehensive intraoperative perfusion analyses using one HSI system only and an ICG-related signal reconstruction framework. Further studies need to address dose and the time dependencies of the combined usage of HSI and ICG. Full article

(This article belongs to the Section Biomedical Optics)

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13 pages, 2587 KB

Open AccessEditor’s ChoiceArticle

Distinct CMR Phenotype in Alcoholic Cardiomyopathy: Greater Myocardial Fibrosis and Right Ventricular Dysfunction Compared with Idiopathic Dilated Cardiomyopathy

by Víctor Vallejo-García, Manuel Barreiro-Pérez, David González-Calle, María del Carmen León del Pino, Victoria Jacas-Osborn, Carlos Barrios and Óscar Fabregat-Andrés

Diagnostics 2026, 16(10), 1560; https://doi.org/10.3390/diagnostics16101560 - 21 May 2026

Viewed by 3830

Abstract

Background/Objectives: Alcoholic cardiomyopathy (ACM) is a major preventable cause of non-ischemic dilated cardiomyopathy (DCM), yet its specific cardiac magnetic resonance (CMR) remains incompletely defined. We aimed to characterize the CMR features of ACM, focusing on late gadolinium enhancement (LGE) subpatterns and biventricular [...] Read more.

Background/Objectives: Alcoholic cardiomyopathy (ACM) is a major preventable cause of non-ischemic dilated cardiomyopathy (DCM), yet its specific cardiac magnetic resonance (CMR) remains incompletely defined. We aimed to characterize the CMR features of ACM, focusing on late gadolinium enhancement (LGE) subpatterns and biventricular function and to compare them with idiopathic DCM. Methods: In total, 148 consecutive patients (ACM n = 20, idiopathic DCM n = 128) referred for CMR at a single center were retrospectively analyzed. Sequential logistic regression adjusted for age, sex, left ventricular ejection fraction (LVEF), and right ventricular ejection fraction (RVEF) was used to identify independent association with LGE presence. Results: LVEF did not differ between groups (32.5% vs. 35.0%, p = 0.293). ACM patients showed significantly worse RVEF (40.5% vs. 52.0%, p = 0.010) and larger indexed right ventricle (RV) volumes. Any LGE was present in 70% vs. 40% (p = 0.015); when the non-specific RV insertion point pattern (non-RV-IP) was excluded, non-RV-IP LGE was 45% vs. 22.7% (p = 0.051), with a specific midwall linear pattern (25% vs. 8%, p = 0.033). ACM was independently associated with LGE across all models with an adjusted odds ratio (OR) of 3.06 [95% CI 1.05–8.95], p = 0.041, and RV dysfunction (RVEF < 45%) (OR 4.79 [95% CI 1.60–14.32], p = 0.005). No differences in major adverse cardiovascular events (MACEs) were observed at 24 months (log-rank p = 0.697). Conclusions: ACM has a distinct CMR phenotype characterized by midwall linear LGE fibrosis and more severe RV involvement, independent of left ventricle (LV) systolic function. These exploratory findings suggest that CMR may provide clinically relevant phenotypic information in ACM beyond LVEF, warranting confirmation in prospective studies. Full article

(This article belongs to the Special Issue Imaging in Cardiomyopathy)

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12 pages, 1418 KB

Open AccessEditor’s ChoiceArticle

Evaluation of Droplet Digital PCR Assay for the Detection of Microsatellite Instability in Colorectal, Gastric, and Endometrial Cancers

by Yousun Chung, Sujin Oh, Soo Kyung Nam, Hyunji Kim, Cheol Lee, Gyeong Hoon Kang, Hyeon Jeong Oh, Hye Seung Lee and Kyoung Un Park

Diagnostics 2026, 16(10), 1550; https://doi.org/10.3390/diagnostics16101550 - 20 May 2026

Viewed by 2434

Abstract

Background: Microsatellite instability (MSI) is an important biomarker for the diagnosis of Lynch syndrome and for guiding immunotherapy in various solid tumors. Droplet digital PCR (ddPCR) has emerged as a highly sensitive method for detecting MSI, particularly in circulating tumor DNA (ctDNA). [...] Read more.

Background: Microsatellite instability (MSI) is an important biomarker for the diagnosis of Lynch syndrome and for guiding immunotherapy in various solid tumors. Droplet digital PCR (ddPCR) has emerged as a highly sensitive method for detecting MSI, particularly in circulating tumor DNA (ctDNA). This study aimed to evaluate the analytical and clinical performance of a ddPCR assay using three MSI markers (BAT-26, ACVR2A, and DEFB105A/B) in colorectal, gastric, and endometrial cancers. Methods: Formalin-fixed paraffin-embedded (FFPE) samples from 190 patients (83 colorectal, 44 gastric, and 63 endometrial cancers) and 21 plasma samples from patients with metastatic solid tumors were analyzed. MSI status determined by ddPCR was compared with conventional PCR using a pentaplex panel and immunohistochemistry (IHC). Analytical performance, including limit of blank (LoB) and limit of detection (LoD), was evaluated using cell line DNA, and clinical cut-offs were established using receiver operating characteristic analysis. Results: The ddPCR assay demonstrated high analytical sensitivity, with LoD values of 0.075% for BAT-26, 0.1% for ACVR2A, and 0.025% for DEFB105A/B. Using optimized clinical cut-offs, the concordance rate between ddPCR and conventional PCR assays was 98.4% in tissue samples. Marker performance varied by cancer type, with reduced sensitivity observed in endometrial cancer. In plasma samples, MSI-H was detected in 1 of 21 cases (4.8%), and the overall concordance rate with tissue-based MSI status was 94.7%. Conclusions: The ddPCR assay demonstrated high concordance with conventional MSI testing methods and showed potential as a sensitive tool for MSI detection in both tissue and plasma samples. However, optimization of marker panels and establishment of sample-type-specific clinical cut-offs are required, particularly for ctDNA-based analysis. Further large-scale studies are needed to validate the clinical utility of ddPCR for MSI detection and monitoring. Full article

(This article belongs to the Special Issue Advances in Laboratory Markers of Human Disease—2nd Edition)

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33 pages, 1883 KB

Open AccessEditor’s ChoiceReview

Fibroblast Activation Protein Inhibitor (FAPI) PET: A Scoping Review of Emerging Oncologic and Fibroinflammatory Applications

by Emmanouil Panagiotidis, Filippos Koinis, Jules Zhang-Yin, George Angelidis, Varvara Valotassiou, Ioannis Tsougos, Athanasios Kotsakis and Panagiotis Georgoulias

Diagnostics 2026, 16(10), 1542; https://doi.org/10.3390/diagnostics16101542 - 19 May 2026

Cited by 1 | Viewed by 1863

Abstract

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. It summarizes advances in fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) for oncologic and fibroinflammatory diseases. FAP is [...] Read more.

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. It summarizes advances in fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) for oncologic and fibroinflammatory diseases. FAP is expressed broadly on activated mesenchymal cells—including cancer-associated fibroblasts (CAFs) and myofibroblasts within desmoplastic tumor stroma, FAP-positive tumor cells in selected sarcomas, and activated fibroblasts in chronic fibroinflammatory disorders such as rheumatoid arthritis, Crohn’s disease, and organ fibrosis. By targeting these activated fibroblasts, [⁶⁸Ga]- and [¹⁸F]-labeled FAPI tracers provide high tumor-to-background contrast, particularly in desmoplastic and stromal-rich cancers. Compared with [¹⁸F]FDG, FAPI PET demonstrates superior lesion conspicuity in selected malignancies and enables a streamlined, non-fasting imaging workflow. Beyond oncology, FAPI PET is emerging as a promising tool for assessing cardiac fibrosis, pulmonary inflammation, and autoimmune conditions characterized by fibroblast activation. A systematic literature search of PubMed and Scopus was performed for peer-reviewed publications from 1 January 2018 to 28 February 2026. Inclusion criteria encompassed original studies, systematic reviews, meta-analyses, clinical guidelines, case series, and case reports reporting on FAPI-targeted PET in human subjects or translational models, published in English. After screening, 256 sources met the eligibility criteria and are included. The development of standardized SNMMI/EANM imaging protocols, along with ongoing multicenter trials and the first prospective phase 2 clinical trial of ⁶⁸Ga-FAPI-46 PET with histopathological confirmation, now supports the reproducible implementation of FAPI PET across institutions. FAPI PET demonstrates strong translational potential, largely due to its favorable biodistribution, safety profile, and theranostic flexibility. However, its widespread use in routine clinical practice is contingent upon large-scale clinical validation, structured reader training, and formal regulatory approval. In conclusion, FAPI PET represents a maturing molecular imaging platform targeting activated fibroblasts across oncologic and fibroinflammatory diseases. Its widespread adoption into clinical practice requires large-scale prospective trials, reader training, standardized reporting, and regulatory approval—all of which are now actively underway. Full article

(This article belongs to the Special Issue Clinical Applications of PET/CT: Current Status and Future Perspectives)

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13 pages, 767 KB

Open AccessEditor’s ChoiceArticle

Lipoprotein(a) as a Risk Factor for Myocardial Infarction, Cardiovascular, and All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

by Jerneja Čuješ, Vojko Kanič, Petra Povalej Bržan and David Šuran

Diagnostics 2026, 16(10), 1520; https://doi.org/10.3390/diagnostics16101520 - 18 May 2026

Viewed by 614

Abstract

Background: Lipoprotein(a) (Lp(a)) is a genetically determined lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). Its prognostic role in type 2 diabetes mellitus (T2DM) remains unclear. We aimed to evaluate the association of Lp(a) with first myocardial infarction (MI), cardiovascular (CV) mortality, and [...] Read more.

Background: Lipoprotein(a) (Lp(a)) is a genetically determined lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). Its prognostic role in type 2 diabetes mellitus (T2DM) remains unclear. We aimed to evaluate the association of Lp(a) with first myocardial infarction (MI), cardiovascular (CV) mortality, and all-cause mortality, with a focus on sex differences. Methods: We retrospectively analysed patients with T2DM and no prior MI who were hospitalised between 2000 and 2018 and had baseline Lp(a) measurements. Patients were followed until MI, death, or the end of 2023. Lp(a) was categorised as ≤50, 51–90, and >90 mg/dL. Cox proportional hazards models were adjusted for low-density lipoprotein cholesterol, arterial hypertension, and estimated glomerular filtration rate < 60 mL/min/1.73 m², with attained age used as the time scale. Results: A total of 2967 patients (37.5% women) were included. During follow-up, 12.5% of patients experienced MI, 36.4% died from CV causes, and 68.8% died from any cause. A significant interaction between Lp(a) and sex was observed for MI. In sex-specific analyses, Lp(a) > 50 mg/dL was associated with a higher risk of first MI in women (51–90 mg/dL: HR 1.79, 95% CI 1.07–2.99; >90 mg/dL: HR 2.67, 95% CI 1.66–4.32), whereas no significant association was observed in men. Elevated Lp(a) ≥ 50 mg/dL was also associated with higher CV mortality overall (51–90 mg/dL: HR 1.42, 95% CI 1.07–1.89; >90 mg/dL: HR 1.38, 95% CI 1.01–1.91), without a significant interaction with sex. No significant associations were observed for all-cause mortality. Conclusions: In patients with T2DM, elevated Lp(a) > 50 mg/dL was associated with increased risk of first MI, predominantly in women, and with higher CV mortality overall. Lp(a) may serve as a valuable marker for CV risk stratification in this population. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management in Cardiology)

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13 pages, 1775 KB

Open AccessEditor’s ChoiceReview

Comprehensive Gene Panel Analysis of Biliary Tract Cancer Using Next-Generation Sequencing of Endoscopic Transpapillary Brushing/Biopsy/Aspiration Specimens: A Narrative Review

by Masaki Kuwatani and Naoya Sakamoto

Diagnostics 2026, 16(10), 1516; https://doi.org/10.3390/diagnostics16101516 - 16 May 2026

Viewed by 548

Abstract

The undesired prognosis of biliary tract cancer is mainly attributed to the difficulty in detecting cancer lesions, including intraepithelial neoplasia, and other hurdles in procuring sufficient pathological samples by forceps biopsy and brushing, or even their combination. However, the transpapillary approach under endoscopic [...] Read more.

The undesired prognosis of biliary tract cancer is mainly attributed to the difficulty in detecting cancer lesions, including intraepithelial neoplasia, and other hurdles in procuring sufficient pathological samples by forceps biopsy and brushing, or even their combination. However, the transpapillary approach under endoscopic retrograde cholangiopancreatography (ERCP) is the mainstream approach for the work-up and treatment of biliary tract diseases, especially biliary tract cancers, because the ERCP-guided approach efficiently enables simultaneous biliary drainage for the treatment of cholangitis/jaundice and specimen acquisition for the diagnosis of biliary tract lesions. To improve diagnostic accuracy, several studies have been conducted on the feasibility and efficacy of genomic analysis of endoscopic specimens, namely, brushing samples, forceps biopsy samples, and aspiration samples such as bile with sensitivities ranging from 47 to 100%, with specificities ranging from 69 to 100%. Clinical use of genomic analysis remains heterogeneous due to the panel and next-generation sequencing system. For the efficient and precise treatment of patients with biliary tract cancer, future diagnosis and treatment should be based on molecular and genetic analyses. In this article, we review and summarize the comprehensive gene panel analyses of transpapillary brushing/biopsy/aspiration specimens for biliary tract cancer using next-generation sequencing, promoting effective clinical practice and providing a basis for future studies. Full article

(This article belongs to the Special Issue Endoscopic Diagnostics for Pancreatobiliary Disorders 2025–2026)

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18 pages, 2533 KB

Open AccessEditor’s ChoiceArticle

Immunohistochemical Study of the Tumor Immune Microenvironment in Laryngeal Squamous Cell Carcinoma and Its Prognostic Implications

by Mihaela-Iuliana Sirbu, Flavia Zara, Raluca Maria Closca, Marina Rakitovan, Antonia Armega-Anghelescu, Alexandru Cristian Cindrea, Ovidiu-Alexandru Mederle, Marcela-Maria Labadi and Nicolae-Constantin Balica

Diagnostics 2026, 16(10), 1431; https://doi.org/10.3390/diagnostics16101431 - 8 May 2026

Viewed by 849

Abstract

Background/Objectives: Laryngeal squamous cell carcinoma exhibits marked heterogeneity in clinical behavior, which cannot be fully explained by conventional histopathological parameters alone. Increasing evidence highlights the pivotal role of the tumor immune microenvironment in modulating tumor progression and patient prognosis. Methods: The [...] Read more.

Background/Objectives: Laryngeal squamous cell carcinoma exhibits marked heterogeneity in clinical behavior, which cannot be fully explained by conventional histopathological parameters alone. Increasing evidence highlights the pivotal role of the tumor immune microenvironment in modulating tumor progression and patient prognosis. Methods: The study group had 82 patients with laryngeal squamous cell carcinoma. A panel of immunohistochemical markers was chosen to identify and quantify key immune cell populations and immune-related components within the tumor immune microenvironment. Semiquantitative evaluation of immune infiltrates was conducted, with particular emphasis on their density and relative distribution across intratumoral and stromal compartments. Results: Based on the resulting immunophenotypic profiles, cases were categorized into three distinct immune patterns: an active immune type, defined by a prominent and dense inflammatory infiltrate; a mixed type, exhibiting intermediate and heterogeneous immune characteristics; and an immunosuppressive type, characterized by reduced effector immune cell infiltration and a predominance of immunoregulatory elements. Statistical analysis demonstrated significant correlations between these immune patterns and patient survival outcomes. Conclusions: The present study aimed to characterize the immune landscape of laryngeal squamous cell carcinoma using immunohistochemical markers and to evaluate its prognostic significance. Full article

(This article belongs to the Special Issue Pathology and Diagnosis of Head and Neck Diseases)

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32 pages, 10352 KB

Open AccessEditor’s ChoiceReview

Ultrasound-Based Techniques for Visualization of Dermal Microvasculature: A Scoping Review

by Rikke Baarts, Alexander Cuculiza Henriksen, Nathalie Sarup Panduro, Emma Kanchana Ertner Bengtsson, Ali Salari, Caroline Clausen, Lisbet Rosenkrantz Hölmich, Lars Lönn, Charlotte Mehlin Sørensen, Jørgen Arendt Jensen and Michael Bachmann Nielsen

Diagnostics 2026, 16(10), 1435; https://doi.org/10.3390/diagnostics16101435 - 8 May 2026

Cited by 1 | Viewed by 3498

Abstract

Objectives: To systematically map the existing literature on ultrasound-based techniques for non-invasive visualization of the dermal microvasculature and identify methodological strengths, limitations, and evidence gaps. Methods: This scoping review was conducted according to PRISMA-ScR guidelines and registered on the Open Science Framework (DOI: [...] Read more.

Objectives: To systematically map the existing literature on ultrasound-based techniques for non-invasive visualization of the dermal microvasculature and identify methodological strengths, limitations, and evidence gaps. Methods: This scoping review was conducted according to PRISMA-ScR guidelines and registered on the Open Science Framework (DOI: 10.17605/OSF.IO/7VDUK). MEDLINE, PubMed, Embase, Scopus, and Web of Science were searched (January 2000–October 2025). Studies involving human participants and ultrasound-based techniques explicitly aimed at visualizing dermal microvasculature were included. Data on study design, population characteristics, imaging parameters, and reported outcomes were extracted and synthesized narratively. Results: Thirty-six studies published between 2007 and 2025 were included. Most were small feasibility or experimental studies (n = 24), with a median sample size of three participants and substantial heterogeneity in imaging protocols. Photoacoustic-based techniques were most frequently reported (n = 21) and were the most consistently described as providing high microvascular detail and functional assessment capability. High-frequency ultrasound (n = 10) and advanced Doppler methods (n = 7) also enabled visualization of dermal vessels, but showed variability in sensitivity, reporting, and standardization. Validation against histopathology was reported in only one study. Conclusions: Ultrasound-based techniques can visualize dermal microvasculature in vivo; however, evidence remains fragmented, methodologically heterogeneous, and largely derived from small exploratory studies. Standardized imaging protocols, pathology-based clinical cohorts and robust validation studies are required to establish comparative performance and enable clinical translation in radiology. Full article

(This article belongs to the Special Issue Ultrasound Imaging in Medicine in 2026)

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24 pages, 884 KB

Open AccessEditor’s ChoiceArticle

Congenital Gastrointestinal Malformations in a Romanian Tertiary Centre (2020–2024): A Retrospective Cohort Study of Diagnosis, Distribution, and Outcomes

by Iulia Stratulat-Chiriac, Raluca Ozana Chistol, Lăcrămioara Perianu, Elena Țarcă, Viorel Țarcă, Alina Mariela Murgu, Paula Popovici, Ioana-Alina Halip, Elena Cojocaru, Valeriu Chisălău and Cristina Furnică

Diagnostics 2026, 16(9), 1408; https://doi.org/10.3390/diagnostics16091408 - 6 May 2026

Cited by 1 | Viewed by 527

Abstract

Background/Objectives: Congenital gastrointestinal malformations (CGIMs) are important causes of neonatal surgical morbidity with potential long-term consequences. Although some can be suspected on prenatal ultrasound, data on their clinical spectrum, burden, and distribution remain limited in Eastern Europe. This study aimed to describe the [...] Read more.

Background/Objectives: Congenital gastrointestinal malformations (CGIMs) are important causes of neonatal surgical morbidity with potential long-term consequences. Although some can be suspected on prenatal ultrasound, data on their clinical spectrum, burden, and distribution remain limited in Eastern Europe. This study aimed to describe the diagnostic spectrum, timing of diagnosis, documented prenatal ultrasound suspicion, and the early outcomes of CGIMs managed at a Romanian tertiary referral centre between 2020 and 2024, a period overlapping the COVID-19 pandemic. Methods: We conducted a retrospective, single-centre observational study including all consecutive paediatric patients with a CGIM admitted between January 2020 and December 2024. Cases were analysed by index anatomical diagnosis, phenotypic complexity, and etiologic background. Logistic regression was used to examine factors associated with documented prenatal suspicion and in-hospital mortality, and annual hospital-based CGIM admission rates were modelled with Poisson regression, using the number of paediatric surgical admission as the offset. Results: Among the 231 children (58.9% male), the most frequent diagnoses were persistent omphalomesenteric duct remnants (16%), oesophageal atresia with or without tracheoesophageal fistula (15.6%), and anorectal malformations (13.9%). Documented prenatal ultrasound suspicion was present in 17.7% of pregnancies (41/231) and was likely underestimated because antenatal documentation was unavailable for 17.7% of the cohort. The highest proportions of documented prenatal suspicion were observed in jejuno-ileal and duodenal atresia. Foregut malformations were the most common by embryological grouping (93/231, 40.3%). Most cases were diagnosed during the neonatal period (n = 161, 69.7%). CGIM admission rates per 1000 surgical admissions ranged from 20.8 to 38.2. An exploratory Poisson model yielded a hospital-based rate ratio per calendar year of 0.88 (95% CI 0.81–0.97; p = 0.008). However, given the limited number of annual observations and increasing total surgical admissions, this finding should be considered exploratory and hypothesis-generating only. Complex cases accounted for 8.2% and associated extra-intestinal anomalies were present in 70.1%. In-hospital mortality was 13.0% and occurred predominantly in patients with complex or foregut malformations. In the primary complete-case multivariable model, prematurity remained independently associated with mortality, whereas complex CGIMs were not independently associated with mortality after adjustment. A prespecified multiple-imputation sensitivity analysis yielded a stronger estimate for complex CGIMs, but this finding was interpreted cautiously and not treated as a primary result. Conclusions: In this tertiary referral cohort, documented prenatal suspicion of CGIM was low and strongly diagnosis-dependent, while most cases were identified in the neonatal period. Mortality was concentrated in foregut and clinically complex presentations in the descriptive analysis, while prematurity remained independently associated with death in the primary multivariable model. These findings highlight the need to strengthen prenatal referral pathways and coordinated national surveillance. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management in Pediatric Surgery)

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14 pages, 3877 KB

Open AccessEditor’s ChoiceArticle

Endocrine Autoimmunity and Inflammatory Signatures in Pediatric Celiac Disease: Context-Dependent Patterns

by Marta Greco, Maria Mirabelli, Roberta Misiti, Francesco Dragone, Annalidia Donato, Denise Casella, Antonio Torchia, Daniela Concolino, Antonio Brunetti and Daniela P. Foti

Diagnostics 2026, 16(9), 1330; https://doi.org/10.3390/diagnostics16091330 - 28 Apr 2026

Viewed by 714

Abstract

Background: Celiac disease (CD) is frequently associated with autoimmune disorders such as Hashimoto’s thyroiditis and type 1 diabetes. Endocrine-specific autoantibodies may emerge during the course of CD, but their true prevalence and clinical relevance in children remain unclear. This study evaluated endocrine autoantibodies [...] Read more.

Background: Celiac disease (CD) is frequently associated with autoimmune disorders such as Hashimoto’s thyroiditis and type 1 diabetes. Endocrine-specific autoantibodies may emerge during the course of CD, but their true prevalence and clinical relevance in children remain unclear. This study evaluated endocrine autoantibodies and inflammatory profiles in pediatric CD to inform a more tailored diagnostic approach. Methods: In this retrospective cross-sectional study, 240 consecutive children referred to a tertiary center for suspected CD and/or autoimmune endocrine disorders were included. CD was diagnosed according to ESPGHAN criteria. Laboratory evaluation comprised blood counts, metabolic parameters, thyroid function tests, thyroid autoantibodies (anti-TPO, anti-Tg), and type 1 diabetes-related autoantibodies (GAD, IA-2, ZnT8). A subgroup of children with CD (n = 28) underwent exploratory multiplex cytokine analysis. Results: Children with CD were slightly older and more often female than controls. Platelet counts were modestly lower in CD, while other hematologic parameters were similar. Thyroid autoimmunity prevalence did not differ significantly (anti-TPO: 2.7% in CD vs. 5.4% in controls; p = 0.348), and antibody titers and TSH levels were comparable. Anti-TPO positivity was associated with older age (p = 0.038), independent of CD status. Islet autoantibodies were similarly distributed between groups. Cytokine levels were not associated with tTG-IgA status; however, girls with CD showed higher IL-2, IL-4, and IL-10 levels than boys (all p < 0.05), with a trend toward higher IL-1α. Conclusions: In this pediatric cohort enriched for immune and endocrine concerns, CD was not linked to increased thyroid or pancreatic autoimmunity. Distinct sex-related differences in inflammatory profiles were observed, suggesting distinct immune patterns in girls with CD. These findings support a clinically driven rather than routine approach to endocrine autoantibody screening and warrant further studies on cytokine-based immune stratification. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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36 pages, 72381 KB

Open AccessEditor’s ChoiceReview

Magnetic Resonance Imaging Features of Hepatic Hydatid Disease: A Pictorial Review with Emphasis on Atypical Presentations and Differential Diagnosis

by Jelena Djokic Kovač, Aleksandra Đikić-Rom, Aleksandra Janković, Nikica Grubor, Aleksandra Đurić-Stefanović, Aleksandar Bogdanović, Milica Mitrović, Ognjan Skrobić, Andrija Antić, Đorđe Knežević, Goran Đuričić, Predrag Zdujić and Nemanja Bidžić

Diagnostics 2026, 16(9), 1304; https://doi.org/10.3390/diagnostics16091304 - 27 Apr 2026

Viewed by 2984

Abstract

Hepatic echinococcosis, caused by Echinococcus species, remains a significant global health concern, with cystic echinococcosis (CE) being widespread and alveolar echinococcosis (AE) representing a rarer but more aggressive form. CE generally demonstrates characteristic imaging features, allowing straightforward diagnosis, whereas atypical presentations can closely [...] Read more.

Hepatic echinococcosis, caused by Echinococcus species, remains a significant global health concern, with cystic echinococcosis (CE) being widespread and alveolar echinococcosis (AE) representing a rarer but more aggressive form. CE generally demonstrates characteristic imaging features, allowing straightforward diagnosis, whereas atypical presentations can closely mimic other hepatic lesions, leading to diagnostic uncertainty. AE poses an even greater diagnostic challenge due to its infiltrative, tumor-like growth pattern. Magnetic resonance imaging (MRI), with its superior soft-tissue contrast and multiplanar capabilities, plays a crucial role in the evaluation of AE and atypical CE cases. This pictorial review summarizes MRI features of hepatic echinococcosis, detailing both typical and atypical appearances, and emphasizes key criteria for differentiating hydatid cysts from other cystic or solid hepatic lesions. By consolidating imaging findings and discussing relevant differential diagnoses, this review aims to improve diagnostic accuracy, guide clinical management, and increase radiologists’ awareness of echinococcosis in both endemic and non-endemic regions. Full article

(This article belongs to the Special Issue Detection and Characterization of Focal Lesions in the Solid Abdominal Organs)

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12 pages, 514 KB

Open AccessEditor’s ChoiceArticle

Utility and Safety of Endosonography in the Diagnosis of Small Cell Lung Cancer: A Prospective Single-Center Observational Study

by Carmine Salerni, Silvia Terraneo, Michele Bonanomi, Sara Mirijaj, Cristina Albrici, Giulia Carone, Letizia Gianoncelli, Mauro Moroni, Umberto Gianelli, Guido Marchi, Paolo Carlucci and Michele Mondoni

Diagnostics 2026, 16(9), 1294; https://doi.org/10.3390/diagnostics16091294 - 26 Apr 2026

Cited by 1 | Viewed by 723

Abstract

Background: Endosonography (i.e., endoscopic ultrasound with bronchoscope fine-needle aspiration, EUS-B-FNA and endobronchial ultrasound-guided transbronchial needle aspiration, EBUS-TBNA) is a widely used technique in the diagnosis and staging of non-small cell lung cancer. Limited data are available in diagnosing small cell lung cancer [...] Read more.

Background: Endosonography (i.e., endoscopic ultrasound with bronchoscope fine-needle aspiration, EUS-B-FNA and endobronchial ultrasound-guided transbronchial needle aspiration, EBUS-TBNA) is a widely used technique in the diagnosis and staging of non-small cell lung cancer. Limited data are available in diagnosing small cell lung cancer (SCLC), and no studies have specifically investigated the diagnostic accuracy of EUS-B-FNA in these patients. The study aims at evaluating the sensitivity and safety of endosonography in the diagnosis of SCLC. Methods: A prospective, single-center, observational study was conducted in Italy. All patients diagnosed with SCLC who underwent EUS-B-FNA and/or EBUS-TBNA were enrolled. The sensitivity of EUS-B-FNA and EBUS-TBNA were assessed using pathological confirmation as the gold standard. Results: A total of 72 patients (38 (53%) males) with confirmed SCLC were included in the study. EUS-B-FNA was performed in 31 (43%) patients and EBUS-TBNA in 44 (61.1%) patients; both procedures were performed in three (4.2%). The overall sensitivity of endosonography was 97.2%. The sensitivity of EUS-B-FNA and EBUS-TBNA was 96.8% and 90.9%, respectively. No differences were observed in the sensitivity of both techniques when sampling lymph nodes vs. pulmonary parenchymal lesions (p = 0.99). The overall complication rate was 5.6%. No major complications were reported. Conclusions: Endosonography is a highly accurate and safe technique in diagnosing SCLC. EUS-B-FNA alone demonstrates excellent sensitivity, supporting its extensive role as a valuable diagnostic tool. The combined use of both techniques may further optimize diagnostic yield in the diagnosis of SCLC. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis and Prognosis of Lung Cancer)

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18 pages, 1597 KB

Open AccessEditor’s ChoiceArticle

Differences in Oral Function, Masticatory Movement, and MRI-Based Structural Features of the Temporomandibular Joint Between the Deviated and Non-Deviated Sides in Patients with Facial Asymmetry

by Rintaro Kubo, Syunnosuke Toyama, Yudai Shimpo, Kiichiro Mizokami, Mari Kaneda, Minami Seki and Hiroshi Tomonari

Diagnostics 2026, 16(9), 1274; https://doi.org/10.3390/diagnostics16091274 - 23 Apr 2026

Viewed by 665

Abstract

Background: Facial asymmetry in patients with dentofacial deformity is often associated with occlusal asymmetry, functional differences in mastication, and temporomandibular joint (TMJ) conditions. However, side-to-side differences in the stability of masticatory movement and their relationship with oral function have not been fully clarified. [...] Read more.

Background: Facial asymmetry in patients with dentofacial deformity is often associated with occlusal asymmetry, functional differences in mastication, and temporomandibular joint (TMJ) conditions. However, side-to-side differences in the stability of masticatory movement and their relationship with oral function have not been fully clarified. Therefore, this study aimed to investigate differences in masticatory movement, oral function, and the prevalence of MRI-based structural features of the temporomandibular joint between the deviated and non-deviated sides in patients with facial asymmetry. Methods: Twenty-one patients with dentofacial deformity and facial asymmetry were included in this study. Oral function was evaluated by measuring occlusal contact area, occlusal force, and masticatory performance. Masticatory movement was recorded using a mandibular movement recording system, and parameters related to the masticatory path and chewing speed were calculated. The stability of masticatory movement was evaluated using the variance of these parameters across chewing cycles. Temporomandibular joint structural features were assessed using CT and MRI. Comparisons between the deviated and non-deviated sides were performed using paired statistical tests. Results: Occlusal contact area and occlusal force were significantly greater on the deviated side than on the non-deviated side (p = 0.001 and p = 0.006, respectively), whereas no significant difference was observed in masticatory performance (p = 0.211). The deviated side showed a smaller closing angle (p = 0.005) and maximum lateral amplitude (p = 0.019), indicating a more vertical chewing pattern. The stability of masticatory movement, evaluated using the variance of masticatory path and velocity parameters, was significantly greater on the deviated side (e.g., variance of cycle axis angle, p = 0.002; variance of maximum closing velocity, p = 0.006). In addition, the prevalence of imaging-based structural features of the temporomandibular joint was significantly higher on the deviated side (p = 0.016). Conclusions: Patients with dentofacial deformity and facial asymmetry were associated with functional asymmetry between the deviated and non-deviated sides. The deviated side showed greater occlusal contact area, occlusal force, and stability of masticatory movement. These findings suggest that the deviated side may be functionally favorable for mastication and may be related to a tendency toward preferential chewing behavior. However, because the habitual chewing side was not directly evaluated in the present study, this interpretation should be considered cautiously and viewed as hypothesis-generating. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Management of Oral Disorders)

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20 pages, 1799 KB

Open AccessEditor’s ChoiceReview

Metabolomic Biomarkers for Monitoring Tuberculosis Treatment Response: A Comprehensive Literature Review

by Hien Thi Thu Nguyen, Tuong Khanh Bui-Nguyen, Chi Que Nguyen, Hanh Thi My Dinh, Trang Khanh Tran, Nhung Thi Thuy Hoang, Huong Minh Nguyen, Vang Le-Quy, Alexei Korobitsyn and Linh Nhat Nguyen

Diagnostics 2026, 16(9), 1278; https://doi.org/10.3390/diagnostics16091278 - 23 Apr 2026

Viewed by 931

Abstract

Tuberculosis (TB) remains a major global cause of morbidity and mortality. Current tools for monitoring treatment response rely on sputum-based microscopy and culture, which are often insensitive, time-consuming, and impractical in extrapulmonary or pediatric TB and in individuals unable to produce sputum. Metabolomics [...] Read more.

Tuberculosis (TB) remains a major global cause of morbidity and mortality. Current tools for monitoring treatment response rely on sputum-based microscopy and culture, which are often insensitive, time-consuming, and impractical in extrapulmonary or pediatric TB and in individuals unable to produce sputum. Metabolomics has emerged as a promising approach for identifying host-derived biomarkers that reflect treatment-associated immunometabolic changes; however, the available evidence remains heterogeneous and has not been comprehensively synthesized. We conducted a comprehensive literature review of human studies evaluating metabolomic biomarkers in relation to TB treatment response or outcomes. PubMed, Scopus, and EMBASE were searched for human studies evaluating targeted or untargeted metabolomics (NMR, LC-MS, GC-MS, CE-MS) in relation to treatment response or outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using QUIPS and PROBAST. Findings were synthesized using a structured framework organized across treatment stages and outcomes. Of 218 records identified, 139 titles and abstracts were screened and 42 full texts assessed; 15 studies met the inclusion criteria. Recurrent treatment-associated signals involved amino acid metabolism, particularly the tryptophan–kynurenine pathway, as well as vitamin and cofactor metabolites (pyridoxate, nicotinamide, trigonelline). Plasma studies frequently reported lipid remodeling and bile acid perturbations, whereas urine studies highlighted polyamine metabolism (e.g., N¹,N¹²-diacetylspermine) and fatty acid β-oxidation markers. Common limitations included inadequate adjustment for confounders and, in prediction models, small sample sizes and limited external validation. Metabolomics reveals reproducible but heterogeneous immunometabolic changes during TB therapy. Key pathways include tryptophan–kynurenine metabolism, vitamin and cofactor metabolism, lipid remodeling, and urine polyamine pathways. Standardization and prospective multicenter validation are needed for clinical translation. Full article

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

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36 pages, 20428 KB

Open AccessEditor’s ChoiceReview

Splenoses and Other Ectopic and Heterotopic Splenic Tissue: The Use of Long-Lasting Enhancement in Contrast-Enhanced Ultrasound to Avoid Unnecessary Intervention

by Kathleen Möller, Siegbert Faiss, Adrian Lim, Christian Jenssen and Christoph F. Dietrich

Diagnostics 2026, 16(8), 1169; https://doi.org/10.3390/diagnostics16081169 - 15 Apr 2026

Cited by 2 | Viewed by 2277

Abstract

This narrative review describes variants of heterotopic and ectopic spleen tissue, focusing on its appearance under contrast-enhanced ultrasound (CEUS) with SonoVue (SonoVue^®; Bracco, Milano, Italy). Typical feature of splenic tissue with SonoVue is its long-lasting enhancement. The diagnosis of these splenic [...] Read more.

This narrative review describes variants of heterotopic and ectopic spleen tissue, focusing on its appearance under contrast-enhanced ultrasound (CEUS) with SonoVue (SonoVue^®; Bracco, Milano, Italy). Typical feature of splenic tissue with SonoVue is its long-lasting enhancement. The diagnosis of these splenic variants, in the vast majority of cases, has primarily been performed with CT, MRI, spleen-specific scintigraphy, or image-guided biopsy. In this review, we analyze published cases and also include our own case examples where CEUS has been used, and describe the enhancement characteristics of splenosis and atypical (intrapancreatic) accessory spleens. CEUS can provide valuable diagnostic information in patients with suspected ectopic splenic tissue, particularly when interpreted together with clinical history and complementary imaging modalities. Ultimately, ectopic splenic tissue should be considered, especially after splenectomy or splenic trauma, in cases of well-defined, hypervascularized lesions where CEUS may help avoid unnecessary invasive procedures in selected cases. Full article

(This article belongs to the Special Issue Recent Advances in Abdominal Imaging)

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15 pages, 1296 KB

Open AccessEditor’s ChoiceArticle

Lifetime Exposure to Endogenous Estradiol and Markers of Dementia Risk: Associations with Later Life Cognitive, Behavioral, and Functional Complaints

by Jasper F. E. Crockford, Dylan X. Guan, Maryam Ghahremani, Clive Ballard, Byron Creese, Anne Corbett, Ellie Pickering, Adam Bloomfield, Pamela Roach, Cindy K. Barha, Eric E. Smith and Zahinoor Ismail

Diagnostics 2026, 16(8), 1146; https://doi.org/10.3390/diagnostics16081146 - 12 Apr 2026

Viewed by 1212

Abstract

Background/Objectives: Longer lifetime exposure to endogenous estradiol (L_EE2) has been associated with lower risk of age-related cognitive decline and dementia. Complementary to cognitive decline, behavioral and functional decline are also predictive of dementia risk; however, the association between L_EE2 [...] Read more.

Background/Objectives: Longer lifetime exposure to endogenous estradiol (L_EE2) has been associated with lower risk of age-related cognitive decline and dementia. Complementary to cognitive decline, behavioral and functional decline are also predictive of dementia risk; however, the association between L_EE2 and these domains is underexplored. We investigated whether L_EE2 is correlated with later-life changes in behavior and function. Methods: Baseline data from 1156 females enrolled in the CAN-PROTECT study were analyzed. L_EE2 was estimated based on the length of the reproductive period (menopause age–menarche age) plus years pregnant and scaled in 5-year increments. Objective cognition was measured using the CAN-PROTECT neuropsychological battery, while subjective cognition, behavior, and function were measured using the Revised Everyday Cognition (ECog-II) scale, Mild Behavioral Impairment Checklist (MBI-C), and Standard Assessment of Global Everyday Activities (SAGEA) scale, respectively. Linear regressions modeled the association between L_EE2 and neuropsychological performance. Three separate negative binomial regression models examined the association between L_EE2 and ECog-II, MBI-C, and SAGEA total scores. All models adjusted for menopause hormone therapy, menopause type, age at first childbirth, body mass index, age, education, and ethnocultural background. Results: Each five-year increase in L_EE2 was associated with a lower MBI-C score (count ratio [CR] = 0.89, 95% CI [0.82, 0.97]) and lower SAGEA score (CR = 0.91, 95% CI [0.84, 0.98]). L_EE2 was not significantly associated with any objective or subjective cognitive measures. Conclusions: Longer L_EE2 may associate with lower severity of later-life behavioral and functional symptoms in older women. Full article

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

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22 pages, 882 KB

Open AccessEditor’s ChoiceReview

Artificial Intelligence for Tuberculosis Screening and Detection: From Evidence to Policy and Implementation

by Hien Thi Thu Nguyen, Vang Le-Quy, Anh Tuan Dinh-Xuan and Linh Nhat Nguyen

Diagnostics 2026, 16(8), 1127; https://doi.org/10.3390/diagnostics16081127 - 9 Apr 2026

Cited by 2 | Viewed by 3128

Abstract

Artificial intelligence (AI) is increasingly used to support tuberculosis (TB) screening and diagnosis, particularly through computer-aided detection (CAD) applied to chest radiography (CXR). However, the programmatic value of AI depends not only on diagnostic accuracy but also on implementation context, threshold calibration, and [...] Read more.

Artificial intelligence (AI) is increasingly used to support tuberculosis (TB) screening and diagnosis, particularly through computer-aided detection (CAD) applied to chest radiography (CXR). However, the programmatic value of AI depends not only on diagnostic accuracy but also on implementation context, threshold calibration, and integration into diagnostic pathways. We conducted a narrative, state-of-the-art review of AI applications across the TB diagnosis pathway. Evidence was synthesized from World Health Organization policy documents, independent validation initiatives, and peer-reviewed studies published between 2010 and 2026, with a structured selection process aligned with PRISMA principles. CAD for CXR is the most mature AI application and is recommended by WHO for TB screening and triage among individuals aged ≥15 years in specific contexts. Across studies, CAD-CXR demonstrates sensitivity comparable to human readers, although performance varies by product, population, and imaging conditions, necessitating local threshold calibration. Evidence from implementation studies suggests improvements in screening efficiency and potential cost-effectiveness in high-burden settings. Other AI modalities, including computed tomography (CT)-based imaging analysis, point-of-care ultrasound interpretation, cough or stethoscope sound analysis, clinical risk models, and genomic resistance prediction show promising but heterogeneous results, with most requiring further independent validation and prospective evaluation. AI has the potential to strengthen TB screening and diagnostic pathways, but its impact depends on integration into health systems and evaluated using patient- and program-level outcomes rather than accuracy alone. A differentiated approach is needed, with responsible scale-up of policy-endorsed tools alongside rigorous evaluation of emerging technologies to support effective and equitable TB care. Full article

(This article belongs to the Special Issue Innovative Approaches to Tuberculosis Screening and Diagnosis)

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17 pages, 1520 KB

Open AccessEditor’s ChoiceArticle

Clinical Value of Core Needle Biopsy as a Second-Line Approach After Non-Conclusive Fine-Needle Aspiration in Thyroid Nodules: A Paired Analysis

by Vladan Markovic, Slobodanka Mitrovic, Tijana Maksic, Irfan Corovic, Marija Sekulic, Mladen Maksic and Vesna Grbovic

Diagnostics 2026, 16(7), 1104; https://doi.org/10.3390/diagnostics16071104 - 7 Apr 2026

Viewed by 746

Abstract

Background: Fine-needle aspiration biopsy (FNAB) is the standard initial diagnostic procedure for thyroid nodules; however, a considerable proportion of results are non-diagnostic or indeterminate, often requiring repeat procedures and delaying management. Core needle biopsy (CNB) has been proposed as a second-line option. This [...] Read more.

Background: Fine-needle aspiration biopsy (FNAB) is the standard initial diagnostic procedure for thyroid nodules; however, a considerable proportion of results are non-diagnostic or indeterminate, often requiring repeat procedures and delaying management. Core needle biopsy (CNB) has been proposed as a second-line option. This study evaluated the frequency of non-conclusive FNAB and CNB results and assessed the diagnostic contribution of CNB in nodules with initially non-conclusive FNAB findings. Methods: A retrospective–prospective study was conducted between 2019 and 2025 at a tertiary referral center, including 434 thyroid nodules. Ultrasound risk stratification followed ACR TI-RADS criteria. FNAB was performed in 430 nodules, and CNB in 85 nodules, including 82 evaluated by both methods. Biopsy results were classified according to the Bethesda system as conclusive or non-conclusive. Paired comparisons were analyzed using the McNemar test, and associations with ultrasound risk were assessed. Results: FNAB produced non-conclusive results in 56.5% of cases, compared with 23.5% for CNB. In paired analysis, 53.7% of nodules with non-conclusive FNAB were reclassified as conclusive after CNB (p < 0.001). CNB significantly distinguished benign from malignant lesions, unlike FNAB. Hypoechogenicity, irregular margins, and punctate echogenic foci were independent predictors of malignancy. Minor complications were more frequent after CNB, while major complications were rare in both groups. Conclusions: CNB improves diagnostic yield when used as a second-line procedure in nodules with non-conclusive FNAB findings. Selective use in higher-risk nodules may reduce repeat procedures and facilitate more structured clinical management. Full article

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

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15 pages, 412 KB

Open AccessEditor’s ChoiceReview

Utility of Colonoscopy After Acute Colonic Diverticulitis

by Miguel Suárez, Raquel Martínez, Ana M. Torres and Jorge Mateo

Diagnostics 2026, 16(7), 1051; https://doi.org/10.3390/diagnostics16071051 - 1 Apr 2026

Cited by 1 | Viewed by 1908

Abstract

Acute diverticulitis (AD) is a common gastrointestinal condition that has seen a significant rise in incidence and prevalence, largely due to the aging population and the increasing prevalence of obesity. Historically, routine colonoscopy was recommended after every episode of AD, but recent studies [...] Read more.

Acute diverticulitis (AD) is a common gastrointestinal condition that has seen a significant rise in incidence and prevalence, largely due to the aging population and the increasing prevalence of obesity. Historically, routine colonoscopy was recommended after every episode of AD, but recent studies and meta-analyses have questioned this practice. Evidence now supports a more selective approach, suggesting that colonoscopy should only be performed in patients with complicated AD, persistent alarm symptoms (abdominal pain, weight loss, altered bowel habits, blood in stool, or iron-deficiency anemia), or imaging findings suggestive of neoplasia. For uncomplicated AD without alarm symptoms, routine colonoscopy is not justified, as it may lead to unnecessary complications and overuse of healthcare resources. Current guidelines reflect this shift, recommending individualized decision-making based on the patient’s clinical history and risk factors. Emerging non-invasive diagnostic tools, such as fecal immunochemical tests (FIT) and artificial intelligence (AI)-based models, hold promise for improving risk stratification and potentially reducing the need for invasive procedures. This narrative review, based on a structured literature search, synthesizes the evolution of post-AD colonoscopy recommendations, presents current evidence, and highlights future research directions on alternative diagnostic methods and their potential to optimize patient care and clinical decision-making. Full article

(This article belongs to the Special Issue New Insights into Endoscopy-Guided Diagnosis)

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22 pages, 639 KB

Open AccessEditor’s ChoiceReview

Precision Approaches to Carbapenem-Resistant Infections in the ICU: Integrating Diagnostics, Stewardship, and Novel Therapies

by Rocco Morena, Sara Palma Gullì, Francesca Serapide and Alessandro Russo

Diagnostics 2026, 16(7), 1053; https://doi.org/10.3390/diagnostics16071053 - 1 Apr 2026

Cited by 2 | Viewed by 2347

Abstract

Carbapenem-resistant Gram-negative infections have become one of the most formidable challenges in intensive care units (ICUs). Critically ill patients—often exposed to invasive procedures, prolonged hospitalization, and broad-spectrum antibiotics—are highly susceptible to infections by carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB). [...] Read more.

Carbapenem-resistant Gram-negative infections have become one of the most formidable challenges in intensive care units (ICUs). Critically ill patients—often exposed to invasive procedures, prolonged hospitalization, and broad-spectrum antibiotics—are highly susceptible to infections by carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB). These pathogens are associated with mortality exceeding 40%, prolonged ICU stays, and increased healthcare costs. Therapeutic advances have reshaped management in recent years. New β-lactam/β-lactamase inhibitor combinations—ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, and sulbactam–durlobactam—along with cefiderocol, have provided safer and more effective alternatives to previously used regimens. Yet, none are universally effective, particularly against carbapenemase-producing organisms, especially metallo-β-lactamase (MBL) producers, and resistance may still emerge during treatment. Rapid molecular and phenotypic diagnostics, when integrated into antimicrobial stewardship, have improved early therapy alignment and reduced unnecessary broad-spectrum use. Beyond antibiotics, colonization surveillance and infection control remain pivotal, as colonization often precedes invasive infection. Biofilm formation on devices such as endotracheal tubes and catheters further promotes persistence and relapse. Strategies targeting biofilm disruption, improved dosing guided by pharmacokinetic/pharmacodynamic optimization, and therapeutic drug monitoring are crucial in ICU practice. The future of managing these infections will depend on integrating precision tools—rapid diagnostics, mechanism-based therapy, and stewardship-guided decisions—with emerging treatments and adjunctive options such as immunomodulators, bacteriophages, and AI-driven decision support. Continued research in ICU-specific populations, especially regarding pharmacokinetics in patients on ECMO or CRRT, is urgently needed. In summary, while the therapeutic landscape for carbapenem-resistant Gram-negative infections has evolved substantially, sustained success will rely on a multifaceted strategy combining innovation, precision, and prevention to improve outcomes for the most vulnerable patients. Full article

(This article belongs to the Special Issue Bacterial Infections and Antimicrobial Resistance: Diagnosis and Management)

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24 pages, 5485 KB

Open AccessEditor’s ChoiceArticle

Development of an Artificial Intelligence-Based System for Evaluating Transthoracic Echocardiographic Imaging in Focus Cardiac Ultrasonography

by Daigo Ikeda, Sanshiro Togo, Shogo Tsuge, Shu Ohya, Yuki Sugiura, Masaya Honda, Taiki Hosokawa, Kenshin Suzuki, Katsumasa Nakamura, Yuki Kurita, Kazuki Tamura and Takeji Saitoh

Diagnostics 2026, 16(7), 1032; https://doi.org/10.3390/diagnostics16071032 - 30 Mar 2026

Viewed by 840

Abstract

Background/Objectives: Transthoracic echocardiography (TTE) is a non-invasive tool for real-time assessment of cardiac motion and blood flow. It is widely used in emergency and bedside settings as a Focus Cardiac Ultrasound (FoCUS) device. However, standardized training methods and adequate educational environments are limited. [...] Read more.

Background/Objectives: Transthoracic echocardiography (TTE) is a non-invasive tool for real-time assessment of cardiac motion and blood flow. It is widely used in emergency and bedside settings as a Focus Cardiac Ultrasound (FoCUS) device. However, standardized training methods and adequate educational environments are limited. Methods: A TTE image assessment artificial intelligence (AI) system was developed in this study, focusing on probe positioning and image quality for non-supervised TTE practice. Results: The view classification model achieved a high F1-score of 0.956. The position evaluation model achieved F1-scores of 0.678, 0.864, and 0.831 for the parasternal long-axis, parasternal short-axis, and apical four-chamber views, respectively. The quality evaluation model achieved F1-scores of 0.674, 0.845, and 0.746. Combining the position and quality models improved the F1-score for the parasternal long-axis view to 0.714, showing the benefit of integrating views with lower baseline performance. Conclusions: This study presents a novel AI-based educational system that assesses probe position and image quality in TTE. The model was developed using a custom dataset of healthy young adults that reflects beginner-level training scenarios, including many suboptimal images similar to those commonly acquired by novices. The proposed framework, which integrates position and quality models, lays the groundwork for future AI-assisted ultrasound training, particularly in unsupervised or resource-limited settings. Full article

(This article belongs to the Special Issue Deep Learning Techniques for Medical Image Analysis)

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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

Cited by 1 | Viewed by 2106

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)

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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

Cited by 1 | Viewed by 2131

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)

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19 pages, 1651 KB

Open AccessEditor’s ChoiceArticle

Differential Diagnosis of Parotid Tumors on Ultrasound: Interobserver Variability and Examiner-Specific Decision Rules—A Machine Learning Approach

by Lukas Pillong, Ida Ohnesorg, Lukas Alexander Brust, Jan Palm, Julia Schulze-Berge, Victoria Bozzato, Manfred Voges, Adrian Müller, Malvina Garner and Alessandro Bozzato

Diagnostics 2026, 16(6), 880; https://doi.org/10.3390/diagnostics16060880 - 16 Mar 2026

Cited by 1 | Viewed by 5350

Abstract

Background/Objectives: Noninvasive differentiation of parotid gland tumors remains challenging despite ultrasound being the primary imaging modality for salivary gland lesions. Given its examiner dependence, improving diagnostic consistency and transparency is crucial. We quantified interobserver variability in parotid ultrasound, modeled examiner-specific decision patterns using [...] Read more.

Background/Objectives: Noninvasive differentiation of parotid gland tumors remains challenging despite ultrasound being the primary imaging modality for salivary gland lesions. Given its examiner dependence, improving diagnostic consistency and transparency is crucial. We quantified interobserver variability in parotid ultrasound, modeled examiner-specific decision patterns using machine learning surrogates, and tested whether surrogate complexity relates to examiner performance. Methods: In this retrospective, single-center study, six examiners independently rated ultrasound images of 149 parotid tumors using predefined descriptors. Performance was summarized using accuracy and the area under the receiver operating characteristic curve (AUC), with 95% confidence intervals (CIs). AUCs were compared using DeLong tests (Holm-adjusted). Interobserver agreement was assessed using pairwise Cohen’s and global Fleiss’ κ. For each examiner, a decision-tree surrogate was trained from structured descriptors and clinical metadata to reproduce examiner labels and visualize decision pathways; performance was estimated by 5-fold cross-validation. Results: Examiner accuracy ranged from 63.5% to 90.5% and AUC from 0.66 to 0.89 (best 0.89, 95% CI 0.83–0.95); the best performer exceeded the two lowest performers (p < 0.001). Agreement was higher for objective descriptors (size: κ = 0.57–0.97) than for subjective descriptors (echogenicity: κ = 0.11–0.79). Surrogate decision-tree accuracy versus histopathology ranged from 57.2% to 80.0% for unpruned and from 65.1% to 76.5% for pruned models, with high coverage (95.3–98.7%). Tree complexity showed no consistent association with examiner performance. Conclusions: Parotid ultrasound shows substantial interobserver variability. Interpretable surrogates can approximate individual labeling behavior from structured descriptors and clinical metadata, making examiner-dependent decision patterns explicit. Full article

(This article belongs to the Special Issue Machine Learning for Medical Image Processing and Analysis in 2026)

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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

Cited by 1 | Viewed by 5303

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)

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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 2123

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)

19 pages, 1345 KB

Open AccessEditor’s ChoiceArticle

A Novel Dual-Modality Dual-View Hybrid Deep Learning–Machine Learning Framework for the Prediction of Carotid Plaque Vulnerability via Late Fusion

by Wenxuan Zhang, Chao Hou, Xinyi Wang, Hongyu Kang, Shuai Li, Yu Sun, Yongping Zheng, Wei Zhang and Sai-Kit Lam

Diagnostics 2026, 16(5), 807; https://doi.org/10.3390/diagnostics16050807 - 9 Mar 2026

Viewed by 1097

Abstract

Background: Ultrasound imaging is an ideal tool for regular carotid plaque screening to identify individuals at high risk of stroke for clinical intervention. However, no existing study leverages multi-modal multi-view ultrasound imaging for AI-enabled auto-classification of carotid plaque vulnerability. This study aims [...] Read more.

Background: Ultrasound imaging is an ideal tool for regular carotid plaque screening to identify individuals at high risk of stroke for clinical intervention. However, no existing study leverages multi-modal multi-view ultrasound imaging for AI-enabled auto-classification of carotid plaque vulnerability. This study aims to develop and validate an effective AI model for carotid plaque vulnerability classification through the applications of dual-modal (B-Mode and contrast-enhanced mode) dual-view (longitudinal and cross-sectional) settings to maximize the utility and potential of ultrasound imaging. Methods: Hybrid deep-learning (DL) and machine-learning (ML) methods were employed to balance between model discriminability and interpretability. B-Mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) images from 241 patients were retrospectively analyzed using the proposed hybrid-DL-ML variants. Results: Our findings suggest the hybrid VGG-RF model developed from a dual-modal dual-view setting outperforms those developed from other settings for identifying vulnerable carotid plaques. The VGG-RF model emerged as the best-performing model, achieving an optimal performance with an AUC of 0.908, precision of 0.765, recall of 0.929, specificity of 0.886, and F1 score of 0.839. The inherent interpretability of the VGG-RF model divulged that long-axis views of BMUS and CEUS images were the major contributing features for discriminating vulnerable carotid plaques against their counterparts. Conclusions: The present study underscored the effectiveness of AI models developed from dual-modal dual-view settings of ultrasound images. Notably, the hybrid VGG-RF model was benchmarked as the best-performing model among other studied hybrid DL-ML variants. Further studies on a larger cohort in a prospective setting are warranted to validate the findings of the current study. Full article

(This article belongs to the Special Issue Artificial Intelligence in Medical Imaging: Innovations and Diagnostic Applications)

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19 pages, 8611 KB

Open AccessEditor’s ChoiceArticle

Co-Localized Dermoscopy and LC-OCT for AI-Assisted Margin Assessment of Basal Cell Carcinoma: Development of a “BCC-One-Stop-Shop” Workflow

by Marco Mozaffari, Clara Tavernier, Jonas Ogien, Pierre Godet, Kristina Fünfer, Hanna Wirsching, Maximilian Deußing, Elke Sattler, Julia Welzel and Sandra Schuh

Diagnostics 2026, 16(5), 750; https://doi.org/10.3390/diagnostics16050750 - 3 Mar 2026

Cited by 5 | Viewed by 1317

Abstract

Background/Objectives: The surgical treatment of basal cell carcinoma (BCC) remains challenging due to the time-consuming, expensive and invasive nature of Mohs micrographic surgery. The objective is to develop a standardized protocol for managing diagnosis, surgery, and margin control within a single patient [...] Read more.

Background/Objectives: The surgical treatment of basal cell carcinoma (BCC) remains challenging due to the time-consuming, expensive and invasive nature of Mohs micrographic surgery. The objective is to develop a standardized protocol for managing diagnosis, surgery, and margin control within a single patient visit. Methods: Several protocols were tested to establish a “BCC-One-Stop-Shop”, combining in vivo and ex vivo margin mapping of BCC, pre- and postoperatively using Line-field confocal optical coherence tomography (LC-OCT). We introduce an algorithm enabling real-time localization of LC-OCT acquisitions on a previously acquired dermoscopy image. Additionally, an artificial intelligence model provides a BCC probability score based on LC-OCT images. Together, the co-localization algorithm and AI BCC model generate a color-coded visualization of the tumor within the dermoscopy image, allowing precise pre-operative in vivo margin assessment. Results: We found our protocol, the implementation of the co-localization tool and the AI model, to be quick to apply, easy to learn and helpful regarding the initial determination of BCC tumor margins. Patients responded positively to the recognizable visualization of the disease. Conclusions: Pre- and postoperative margin mapping using LC-OCT imaging appears to be effective and feasible and could reduce time, costs, resources, excision sizes and patient burden by sparing additional excision steps in micrographic surgery. The integration of real-time co-localization and the AI-calculated probability score represent meaningful and practical enhancements for routine clinical use. To further evaluate the efficacy and safety of the BCC-One-Stop-Shop-Method and the newly introduced device features, larger-scale studies are warranted and are currently being conducted. Full article

(This article belongs to the Special Issue Innovations in Dermatologic Diagnostics: Integrating Dermoscopy, Imaging, and Non-Surgical Therapies)

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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 606

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

Cited by 4 | Viewed by 1261

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)

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15 pages, 2699 KB

Open AccessEditor’s ChoiceArticle

Functional and Structural Analysis of the Central Retina According to the Fundus Autofluorescence Pattern in Patients with Retinitis Pigmentosa

by Marta P. Wiącek, Kinga Skorupińska, Miszela Kałachurska and Anna Machalińska

Diagnostics 2026, 16(4), 597; https://doi.org/10.3390/diagnostics16040597 - 17 Feb 2026

Viewed by 700

Abstract

Background: This study evaluated morphological and functional differences among eyes with retinitis pigmentosa (RP) classified according to fundus autofluorescence (FAF) patterns. Methods: A total of 146 eyes from 73 patients with RP were analysed. Based on FAF imaging, eyes were classified [...] Read more.

Background: This study evaluated morphological and functional differences among eyes with retinitis pigmentosa (RP) classified according to fundus autofluorescence (FAF) patterns. Methods: A total of 146 eyes from 73 patients with RP were analysed. Based on FAF imaging, eyes were classified as having regular hyperautofluorescent rings (n = 23), irregular rings (n = 76), or absent rings (n = 47). Participants underwent best-corrected visual acuity (BCVA), contrast sensitivity, 10–2 and 30–2 static perimetry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). FAF morphometrics included ring diameters and area. Results: Eyes with a regular FAF ring demonstrated significantly better visual function than those with irregular or absent rings, including higher BCVA (p < 0.001 and p = 0.001) and greater contrast sensitivity (both p < 0.001). The mfERG amplitude density in the first ring was higher in regular than irregular FAF patterns (p = 0.034). Eyes with irregular FAF showed more advanced visual field loss, with lower mean deviation on 10–2 (p = 0.042) and 30–2 perimetry (p = 0.027). In the regular-ring group, the ellipsoid zone was predominantly intact (p = 0.012). The hyperautofluorescent ring area correlated positively with mfERG amplitude density in the first and second rings (Rs = +0.573, p = 0.016; Rs = +0.736, p = 0.001) and with macular volume (Rs = +0.667, p = 0.003). Conclusions: FAF patterns reflect central retinal functional and structural impairment in RP. Therefore, incorporating FAF imaging into the diagnostic algorithm is valuable for monitoring disease progression. Full article

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

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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

Cited by 1 | Viewed by 2516

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)

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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 3 | Viewed by 2885

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)

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15 pages, 5376 KB

Open AccessEditor’s ChoiceArticle

Deep Learning-Based Liver Tumor Segmentation from Computed Tomography Scans with a Gradient-Enhanced Network

by Hangyeul Shin, Kyujin Han, Seungyoo Lee, Harin Park, Seunghyon Kim, Jeonghun Kim, Xiaopeng Yang, Jae Do Yang, Jisoo Song, Hee Chul Yu and Heecheon You

Diagnostics 2026, 16(3), 429; https://doi.org/10.3390/diagnostics16030429 - 1 Feb 2026

Cited by 4 | Viewed by 1990

Abstract

Background/Objectives: This study aimed to develop a fully automatic method for liver tumor segmentation based on our previously developed gradient-enhanced network G-UNETR++. Methods: The proposed method consists of segmentation of the full liver region from computed tomography (CT) images using G-UNETR++, [...] Read more.

Background/Objectives: This study aimed to develop a fully automatic method for liver tumor segmentation based on our previously developed gradient-enhanced network G-UNETR++. Methods: The proposed method consists of segmentation of the full liver region from computed tomography (CT) images using G-UNETR++, masking the CT images with the extracted liver region to exclude non-liver regions, and liver tumor segmentation from the masked CT images, also using G-UNETR++. To train and evaluate the model, a total of 131 CT scans (97 for training, 20 for validation, and 20 for testing) from the publicly available LiTS dataset were used. Furthermore, another public dataset, the 3DIRCADb dataset consisting of 20 CT scans was used for cross-validation of the effectiveness and generalizability of our method. Results: Experimental results showed that our method outperformed state-of-the-art models over both the LiTS dataset and the 3DIRCADb dataset, with an average dice score of 0.844 and 0.832 over the two datasets, respectively. Conclusions: The proposed method is effective in clinical application to help physicians with liver tumor diagnosis and treatment. Full article

(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)

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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

Cited by 1 | Viewed by 860

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)

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