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Diagnostics, Volume 15, Issue 18 (September-2 2025) – 30 articles

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16 pages, 1547 KB  
Article
Long-Term Retrospective Analysis of Parvovirus B19 Infections in Blood Donors (2012–2024): Significant Increase in Prevalence Following the SARS-CoV-2 Pandemic
by Michaela Oeller, Orkan Kartal, Iuliia Trifonova, Nina Held, Alexandra Domnica Hoeggerl, Heidrun Neureiter, Wanda Lauth, Christoph Grabmer, Eva Rohde and Sandra Laner-Plamberger
Diagnostics 2025, 15(18), 2313; https://doi.org/10.3390/diagnostics15182313 - 11 Sep 2025
Abstract
Background/Objectives: Parvovirus B19 (B19V) is a non-enveloped single-stranded DNA virus transmissible by blood transfusion, with potentially severe outcomes in immunocompromised and pregnant recipients. In this study, we investigated the B19V prevalence in 441,084 blood donations from Salzburg, Austria, collected between 2012 and [...] Read more.
Background/Objectives: Parvovirus B19 (B19V) is a non-enveloped single-stranded DNA virus transmissible by blood transfusion, with potentially severe outcomes in immunocompromised and pregnant recipients. In this study, we investigated the B19V prevalence in 441,084 blood donations from Salzburg, Austria, collected between 2012 and 2024, focusing on changes in epidemiological dynamics before, during, and after the SARS-CoV-2 pandemic. Additionally, the B19VB19V persistence and its implications for deferral policies were assessed. Methods: Donor samples were screened for B19VB19V DNA by qPCR (2012–2024) and for SARS-CoV-2 total anti-N antibodies (2020–2024). B19VB19V prevalence rates, cycle threshold (Ct) values, and seasonal distribution were compared between pre-pandemic, pandemic, and post-pandemic phases. Follow-up testing of initially B19VB19V-positive donors was performed after a 2-year deferral period. Results: The B19VB19V positivity rate of 0.13% (2012–2019) significantly decreased to 0.02% during the SARS-CoV-2 pandemic (2020–2022). A substantial increase occurred post-pandemic, with prevalence reaching 1.47% in 2024. Significant lower Ct values were observed in the post-pandemic phase, indicating higher viral loads. Additionally, younger donors (aged 18–45 years) showed significantly lower Ct values. After a 2-year deferral, 39% of re-tested donors remained B19VB19V DNA-positive. Conclusions: B19VB19V circulation increased substantially after the SARS-CoV-2 pandemic. Our observation is consistent with international reports and is likely due to an ‘immunity debt’ that has been accumulated due to pandemic-related public health interventions. Targeted B19VB19V screening and strict deferral strategies may be warranted particularly during outbreak periods to protect high-risk transfusion recipients. Full article
8 pages, 654 KB  
Interesting Images
A Cystic-like Lesion of Uncertain Origin—A Discussion on Cemento-Osseous Dysplasia and Traumatic Bone Cysts
by Kamil Nelke, Maciej Karpiński, Michał Scharoch, Maciej Janeczek, Agata Małyszek, Evagelos Kalfarentzos, Efthymios Mavrakos, Piotr Kuropka, Christos Perisanidis and Maciej Dobrzyński
Diagnostics 2025, 15(18), 2312; https://doi.org/10.3390/diagnostics15182312 - 11 Sep 2025
Abstract
Mandible cemento-osseous dysplasia (COD) can be found mostly associated with dental roots and tooth-bearing anatomical structures. A variety of odontogenic cysts and tumors might have similar appearances. A lesion in the jaw bone not associated with dental roots with a cyst-like appearance might [...] Read more.
Mandible cemento-osseous dysplasia (COD) can be found mostly associated with dental roots and tooth-bearing anatomical structures. A variety of odontogenic cysts and tumors might have similar appearances. A lesion in the jaw bone not associated with dental roots with a cyst-like appearance might suggest a non-odontogenic lesion, an empty bone cavity, an osseous, fibrous, or fibro-osseous lesion, or a traumatic bone cyst (TBC). A radiolucent irregular bone cavity without clear borders always requires improved diagnostics in cone-beam computed tomography (CBCT) as well as a revision and a biopsy in some cases. When there is some bone swelling and asymmetry on radiological evaluation, followed by extra-cortical spread, and the lesion has irregular borders with thickening or atypical calcifications, a biopsy should be performed. COD and TBCs can be found mostly associated with dental roots, but sometimes they are not associated with tooth-bearing jaw structures and might cause some diagnostic problems, especially if they resemble an empty radiolucent cystic-like lesion in an atypical location. Regardless of the type of lesion, a bone revision and a biopsy are important. When a sufficient amount of a sample is removed and evaluated, this can greatly improve the final diagnosis. The authors present an interesting case of a lesion accidentally found in a routine panoramic radiograph used for screening before scheduled orthodontic treatment. Full article
(This article belongs to the Collection Interesting Images)
15 pages, 4386 KB  
Article
Microstructural Analysis of Whole-Brain Changes Increases the Detection of Pediatric Focal Cortical Dysplasia
by Xinyi Yang, Shuang Ding, Song Peng, Wei Tang, Yali Gao, Zhongxin Huang and Jinhua Cai
Diagnostics 2025, 15(18), 2311; https://doi.org/10.3390/diagnostics15182311 - 11 Sep 2025
Abstract
Purpose: Focal cortical dysplasia (FCD) is a common developmental malformation disease of the cerebral cortex. Although mounting evidence has suggested that FCD lesions have variable locations and topographies throughout the cortex, few studies have explored consistencies in structural connectivity among different lesion [...] Read more.
Purpose: Focal cortical dysplasia (FCD) is a common developmental malformation disease of the cerebral cortex. Although mounting evidence has suggested that FCD lesions have variable locations and topographies throughout the cortex, few studies have explored consistencies in structural connectivity among different lesion types. In this study, we analyzed microscopic structural changes via lesion analysis and explored structural changes in nonlesion regions across the brain. Methods: Diffusion tensor imaging (DTI) and magnetization transfer imaging were used to compare FCD lesions and contralateral normal appearing gray/white matter (cNAG/WM). Voxel-based morphometry was calculated for 28 children with FCD and 34 sex- and age-matched healthy participants. DTI indices of the FCD and healthy control groups were analyzed via the tract-based spatial statistic method to evaluate the microstructure abnormalities of WM fiber tracts in individuals with FCD. Results: In terms of FCD lesions, compared with those of the cNAG, the fractional anisotropy (FA) values were decreased, and the mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were increased; the magnetization transfer ratios were also decreased. In terms of whole-brain changes due to FCD, compared with the healthy control group, the FCD group showed a decrease in the volume of the right hippocampus and left anterior cingulate cortex. FCD patients had lower FA values, higher MD values, lower AD values, and mainly increased RD values in relation to WM microstructure. Conclusions: Microstructural abnormalities outside lesion regions may be related to injury to the epileptic network, and the identification of such abnormalities may complement diagnoses of FCD in pediatric patients. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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19 pages, 3431 KB  
Article
Computed Tomography Radiomics and Machine Learning for Prediction of Histology-Based Hepatic Steatosis Scores
by Winston T. Chu, Hui Wang, Marcelo A. Castro, Venkatesh Mani, C. Paul Morris, Thomas C. Friedrich, David H. O’Connor, Courtney L. Finch, Ji Hyun Lee, Philip J. Sayre, Gabriella Worwa, Anya Crane, Jens H. Kuhn, Ian Crozier, Jeffrey Solomon and Claudia Calcagno
Diagnostics 2025, 15(18), 2310; https://doi.org/10.3390/diagnostics15182310 - 11 Sep 2025
Abstract
Background/Objective: Computed tomography (CT) can be used to non-invasively assess the health of the liver; however, radiologist evaluation and simple thresholding alone are insufficient for diagnosis of hepatic steatosis, necessitating biopsies. This study explored CT radiomics and machine learning to enable non-invasive, objective, [...] Read more.
Background/Objective: Computed tomography (CT) can be used to non-invasively assess the health of the liver; however, radiologist evaluation and simple thresholding alone are insufficient for diagnosis of hepatic steatosis, necessitating biopsies. This study explored CT radiomics and machine learning to enable non-invasive, objective, and quantitative prediction of steatosis severity across the macaque liver. Methods: In this retrospective study, CT images of 42 crab-eating macaques (age [yr] = 6.1 ± 1.7; sex [male/female] = 26/16) with varying degrees of hepatic steatosis were analyzed, and the results were compared to histology-based steatosis scores of livers from the same animals. After extracting radiomic features, a thorough array of statistical analyses, feature selection techniques, and machine learning models were applied to identify a distinct radiomic signature of histologically defined hepatic steatosis. Results: We identified 12 radiomic features that correlated with steatosis scores, and hierarchical clustering based on radiomic attributes alone revealed clusters roughly aligning with steatosis severity groups. The k-nearest neighbors model architecture best predicted histopathologic steatosis scores in both classification and regression tasks (area under the receiver operating characteristic curve [AUC ROC] = 0.89 ± 0.09; root-mean-square error [RMSE] = 0.60 ± 0.10). Feature analyses identified seven key radiomic features (six first-order features and one gray-level co-occurrence matrix feature) that were most important when predicting steatosis. Conclusions: We identified a CT radiomic signature of steatosis and demonstrated that histology-based steatosis scores can be predicted non-invasively and objectively using machine learning and CT radiomics as a potential alternative to invasive core biopsies. Given the strong similarities in liver structure, liver function, and hepatic steatosis pathophysiology between macaques and humans, these findings have the potential to translate to humans. Full article
(This article belongs to the Special Issue Artificial Intelligence-Driven Radiomics in Medical Diagnosis)
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18 pages, 760 KB  
Article
Antineutrophil Cytoplasmic Autoantibodies Specific to Bactericidal/Permeability-Increasing Protein: A Cross-Road Between Prolonged Gram-Negative Bacterial Infections and Ulcerative Colitis/Primary Sclerosing Cholangitis
by Dragana Jovanovic, Rada Miskovic, Aleksandra Plavsic, Sara Radovic, Ljudmila Nagorni-Obradovic, Dragan Popovic, Milos M. Nikolic and Branka Bonaci-Nikolic
Diagnostics 2025, 15(18), 2309; https://doi.org/10.3390/diagnostics15182309 - 11 Sep 2025
Abstract
Background/Objectives: Binding of bactericidal/permeability-increasing (BPI) protein to Gram-negative (GN) bacteria plays a major role in bacterial elimination. The relationship between BPI-antineutrophil cytoplasmic autoantibodies (ANCA), persistent infections and immunoinflammatory diseases has not been elucidated. Methods: In total, 193 ANCA-positive patients detected by [...] Read more.
Background/Objectives: Binding of bactericidal/permeability-increasing (BPI) protein to Gram-negative (GN) bacteria plays a major role in bacterial elimination. The relationship between BPI-antineutrophil cytoplasmic autoantibodies (ANCA), persistent infections and immunoinflammatory diseases has not been elucidated. Methods: In total, 193 ANCA-positive patients detected by IIF with ANCA-associated vasculitides (AAV, n-40), connective tissue diseases (CTD, n-28), drug-induced vasculitides (DIV, n-17), ulcerative colitis (UC, n-24), UC with primary sclerosing cholangitis (UC/PSC, n-14), Crohn’s disease (CD, n-10), autoimmune hepatitis (AIH, n-19) and chronic infections (n-41) were tested using the BPI-ANCA quantitative and semiquantitative ELISA (ANCA-profile: BPI, proteinase 3, myeloperoxidase, elastase, cathepsin G, lactoferrin). BPI-ANCA were analyzed in 52 healthy persons. Results: A total of 46/193 (23.8%) patients had BPI-ANCA positivity. BPI-ANCA were more frequently present in patients with prolonged GN bacterial infections and inflammatory bowel diseases than in AAV, DIV, AIH, CTD and healthy controls (p < 0.001). UC/PSC patients more frequently had BPI-ANCA than UC and CD patients (p < 0.001). GN bacterial infections more frequently had BPI-ANCA than Gram-positive bacterial infections (p < 0.001). Infections caused by Pseudomonas aeruginosa and Mycobacterium tuberculosis had monospecific BPI-ANCA (sensitivity 79% and 71%, respectively). UC/PSC and chronic GN bacterial infections caused by Klebsiella pneumoniae, Proteus mirabilis, or Escherichia coli had multispecific BPI-ANCA (sensitivity 64% and 100%, respectively). Odds ratio analysis showed that patients with IBD who were positive for multispecific BPI-ANCA had a 13.5-fold increased risk of UC/PSC (95% CI 2.98–61.18). Conclusions: Monospecific BPI-ANCA may be a valuable biomarker for persistent Pseudomonas aeruginosa and Mycobacterium tuberculosis infections. In contrast, multispecific BPI-ANCA are associated with UC/PSC and persistent infections caused by intestinal Gram-negative bacteria. Suppression of antimicrobial function by multispecific BPI-ANCA could impair the elimination of Gram-negative bacteria, sustaining the immunoinflammation. Dysregulated antimicrobial response might be the target of immunomodulatory therapy in the initial phase of BPI-ANCA-positive UC/PSC. Full article
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16 pages, 957 KB  
Review
The Rise of AI-Assisted Diagnosis: Will Pathologists Be Partners or Bystanders?
by Riyad El-Khoury and Ghazi Zaatari
Diagnostics 2025, 15(18), 2308; https://doi.org/10.3390/diagnostics15182308 - 11 Sep 2025
Abstract
Over 150 years, pathology has transformed remarkably, from the humble beginnings of microscopic tissue examination to today’s revolutionary advancements in digital pathology and artificial intelligence (AI) applications. This review briefly retraces the evolution of microscopes and highlights breakthroughs in complementary tools and techniques [...] Read more.
Over 150 years, pathology has transformed remarkably, from the humble beginnings of microscopic tissue examination to today’s revolutionary advancements in digital pathology and artificial intelligence (AI) applications. This review briefly retraces the evolution of microscopes and highlights breakthroughs in complementary tools and techniques that laid the foundation for modern surgical pathology, recently expanded into a new dimension with digital pathology. Digital pathology marked a pivotal turning point by addressing the longstanding limitations of conventional microscopy, paving the way for AI integration. AI now revolutionizes pathology workflows, offering unprecedented opportunities for automated diagnostics, enhanced precision, accelerated research, and advanced medical education. Despite widespread consensus on AI as complementary to pathologists, rare studies critically explore the feasibility of a fully autonomous, pathologist-independent diagnostic workflow. Given the rapid advancement of AI, it is timely to examine whether mature AI systems might realistically achieve diagnostic autonomy. Thus, this review uniquely addresses this gap by evaluating the feasibility, limitations, and implications of a disruptive, pathologist-free diagnostic model. This exploration raises critical questions about the evolving role of pathologists in an era increasingly defined by automation. Can pathologists adapt to emerging trends, maintain their central role in patient care, and leverage AI effectively, or will their traditional roles inevitably diminish? Could the continued advancement of AI eventually prompt a return of pathologists to their initial mid-19th century role as scientist scholars, removed from frontline diagnostics? Ultimately, we assess whether AI can independently sustain diagnostic accuracy and decision making without pathologist oversight. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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9 pages, 201 KB  
Communication
Criteria for Routine Laboratory Blood Tests in Patients Hospitalized in Cardiology Departments
by Zvi Shimoni, Fadi Hin and Paul Froom
Diagnostics 2025, 15(18), 2307; https://doi.org/10.3390/diagnostics15182307 - 11 Sep 2025
Abstract
The proportion of laboratory tests ordered in cardiology departments without clinical utility is unclear. The objective of this study was to determine if criteria limiting testing can safely reduce admission and follow-up testing. We reviewed the charts of 471 consecutive patients admitted to [...] Read more.
The proportion of laboratory tests ordered in cardiology departments without clinical utility is unclear. The objective of this study was to determine if criteria limiting testing can safely reduce admission and follow-up testing. We reviewed the charts of 471 consecutive patients admitted to the cardiology department at a regional hospital from January 2019 to June 2019. We prospectively set appropriate criteria for routine admission and follow-up testing. Commonly ordered tests and parameters considered not to be indicated either on admission or on follow-up included C-reactive protein, liver function tests, lactate dehydrogenase, creatine phosphokinase, calcium, blood urea nitrogen, uric acid, cholesterol, Hemoglobin A1c, and prothrombin times (except for patients treated with warfarin). Admission tests considered appropriate included electrolytes, glucose, creatinine, and complete blood counts. Follow-up testing was indicated only if test results were outside the reference ranges. Troponin tests were only indicated if needed to determine the need for a coronary angiogram. The outcome variables were the proportion of indicated tests and whether tests outside the criteria led to changes in acute care that positively affected the patient’s hospital care. In the 471 patients, there were 18,061 tests ordered (not including troponin), and 14,427 (79.9%) were not indicated; this led to 46 (0.3%) changes in medical care, which did not affect the patients’ clinical course. There were 47.8% (364/761) troponin tests that were not indicated and did not change patient care. Our study suggests that interventions in cardiology departments such as ours could safely reduce troponin testing by nearly 50% and other laboratory tests by around 80%. These results need to be confirmed in other settings and in interventional studies. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
11 pages, 717 KB  
Article
[123I]-Meta-Iodobenzylguanidine Scintigraphy in Sarcoidosis: Exploring Cardiac Autonomic Dysfunction in Patients with Unexplained Cardiac Symptoms
by Lisette R. M. Raasing, Marjolein Drent, Ruth G. M. Keijsers, Andor F. van den Hoven, Marco C. Post, Jan C. Grutters and Marcel Veltkamp
Diagnostics 2025, 15(18), 2306; https://doi.org/10.3390/diagnostics15182306 - 11 Sep 2025
Abstract
Background/Objectives: Sarcoidosis is a systemic inflammatory disease that can cause cardiac autonomic dysfunction (SCAD), often underrecognized despite its clinical importance. While [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and cardiac magnetic resonance imaging (CMR) assess cardiac involvement, [ [...] Read more.
Background/Objectives: Sarcoidosis is a systemic inflammatory disease that can cause cardiac autonomic dysfunction (SCAD), often underrecognized despite its clinical importance. While [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and cardiac magnetic resonance imaging (CMR) assess cardiac involvement, [123I]-meta-iodinebenzylguanidine ([123I]MIBG) scintigraphy evaluates cardiac sympathetic innervation, offering complementary insights to potentially improve SCAD detection and management. This retrospective study explores the role of [123I] MIBG scintigraphy in detecting SCAD among patients with unexplained cardiac symptoms. It focuses on its potential to provide complementary diagnostic information in patients where established imaging techniques, such as [18F]FDG PET/CT and CMR, fail to detect cardiac sarcoidosis. Methods: Sarcoidosis patients referred to the St. Antonius Hospital (2017–2024) who underwent [123I]MIBG scintigraphy were included. Collected data encompassed demographics, SCAD symptoms, cardiac imaging findings, and carvedilol treatment outcomes. [123I] MIBG abnormalities were defined as a heart-to-mediastinal ratio ≤1.6 or a washout rate ≥20%. Results: Among the final cohort of 40 sarcoidosis patients with unexplained cardiac symptoms and normal [18F]FDG PET/CT and CMR findings, 19 patients (48%) showed abnormal [123I] MIBG scintigraphy results suggestive of SCAD. No significant differences were observed in clinical characteristics between patients with normal and abnormal [123I]MIBG findings. Of the 16 patients treated with carvedilol, 88% reported symptom improvement, although 50% experienced side effects. Conclusions: [123I]MIBG scintigraphy revealed abnormalities in a substantial number of sarcoidosis patients with unexplained cardiac symptoms despite normal [18F]FDG PET/CT and CMR. These findings indicate a potential role for [123I]MIBG in detecting SCAD, but prospective studies are needed to confirm their clinical significance. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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16 pages, 501 KB  
Review
Radiopharmaceuticals in Malignant Melanoma: A Comprehensive Review of Diagnostic, Therapeutic, and Immune-Related Applications by PET/CT, SPECT/CT, and PET/MRI
by Irina Pirsan and Doina Piciu
Diagnostics 2025, 15(18), 2305; https://doi.org/10.3390/diagnostics15182305 - 11 Sep 2025
Abstract
Background: Malignant melanoma remains an oncological challenge, with advanced-stage five-year survival rates under 20%. Precise molecular imaging has become indispensable for accurate staging, selection of targeted or immunotherapies, treatment response assessment, and early detection of immune-related adverse events. This review examines the roles [...] Read more.
Background: Malignant melanoma remains an oncological challenge, with advanced-stage five-year survival rates under 20%. Precise molecular imaging has become indispensable for accurate staging, selection of targeted or immunotherapies, treatment response assessment, and early detection of immune-related adverse events. This review examines the roles of PET/CT, PET/MRI, and SPECT/CT radiopharmaceuticals in melanoma management and highlights novel tracers and theranostic strategies poised to enhance precision nuclear medicine in this disease. Methods: We performed a review of English-language literature from January 2000 through June 2025, querying PubMed, Scopus, and clinical-trial registries for original research articles, meta-analyses, clinical guidelines, and illustrative case reports. Eligible studies investigated PET/CT, PET/MRI, or SPECT/CT applications in melanoma diagnosis, nodal and distant staging, therapy monitoring, irAE (immune-related adverse events) detection, and the development of emerging radiotracers or theranostic radiopharmaceutical pairs. Results:18F-FDG PET/CT demonstrated a high detection rate for distant metastases, outperforming conventional CT and MRI in advanced disease, despite limited resolution for infracentimetric nodal deposits. PET/MRI offers comparable diagnostic accuracy with superior soft-tissue contrast and improved brain lesion detection, while SPECT/CT enhanced sentinel lymph node localization prior to surgical biopsy. Also, FDG PET/CT identified visceral irAEs with great sensitivities, revealing asymptomatic toxicities in up to one-third of patients. Emerging radiotracers targeting melanin, fibroblast activation protein, PD-1 (programmed cell death protein 1)/PD-L1 (programmed cell death-ligand 1), and CD8+ T cells have demonstrated enhanced tumor specificity and are on their way to forming novel theranostic pairs. Conclusions: While 18F-FDG PET/CT remains the cornerstone of melanoma imaging, complementary advantages of PET/MRI and SPECT/CT imaging refine melanoma management. The advent of highly specific radiotracers and integrated theranostic approaches heralds a new era of tailored nuclear-medicine strategies, promising improved patient stratification, therapy guidance, and clinical outcomes in melanoma. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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24 pages, 5448 KB  
Article
GlioSurvQNet: A DuelContextAttn DQN Framework for Brain Tumor Prognosis with Metaheuristic Optimization
by M. Renugadevi, Venkateswarlu Gonuguntla, Ihssan S. Masad, G. Venkat Babu and K. Narasimhan
Diagnostics 2025, 15(18), 2304; https://doi.org/10.3390/diagnostics15182304 - 11 Sep 2025
Abstract
Background/Objectives: Accurate classification of brain tumors and reliable prediction of patient survival are essential in neuro-oncology, guiding clinical decisions and enabling precision treatment planning. However, conventional machine learning and deep learning methods often struggle with challenges such as data scarcity, class imbalance, limited [...] Read more.
Background/Objectives: Accurate classification of brain tumors and reliable prediction of patient survival are essential in neuro-oncology, guiding clinical decisions and enabling precision treatment planning. However, conventional machine learning and deep learning methods often struggle with challenges such as data scarcity, class imbalance, limited model interpretability, and poor generalization across diverse clinical settings. This study presents GlioSurvQNet, a novel reinforcement learning-based framework designed to address these limitations for both glioma grading and survival prediction. Methods: GlioSurvQNet is built upon a DuelContextAttn Deep Q-Network (DQN) architecture, tailored for binary classification of low-grade vs. high-grade gliomas and multi-class survival prediction (short-, medium-, and long-term categories). Radiomics features were extracted from multimodal MRI scans, including FLAIR, T1CE, and T2 sequences. Feature optimization was performed using a hybrid ensemble of metaheuristic algorithms, including Harris Hawks Optimization (HHO), Modified Gorilla Troops Optimization (mGTO), and Zebra Optimization Algorithm (ZOA). Subsequently, SHAP-based feature selection was applied to enhance model interpretability and robustness. Results: The classification module achieved the highest accuracy of 99.27% using the FLAIR + T1CE modality pair, while the survival prediction model attained an accuracy of 93.82% with the FLAIR + T2 + T1CE fusion. Comparative evaluations against established machine learning and deep learning models demonstrated that GlioSurvQNet consistently outperformed existing approaches in both tasks. Conclusions: GlioSurvQNet offers a powerful and interpretable AI-driven solution for brain tumor analysis. Its high accuracy and robustness make it a promising tool for clinical decision support in glioma diagnosis and prognosis. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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11 pages, 689 KB  
Article
Fetal Cardiovascular Profile Score (CVPs) in Fetal Anemia, Using Fetal Hemoglobin Bart’s Disease at Mid-Pregnancy as a Study Model
by Panisa Hantrakun, Kasemsri Srisupundit and Theera Tongsong
Diagnostics 2025, 15(18), 2303; https://doi.org/10.3390/diagnostics15182303 - 11 Sep 2025
Abstract
Objectives: To evaluate the diagnostic performance of CVPs in predicting fetal Hb Bart’s disease among pregnancies at risk and to study hemodynamic changes based on CVP components in response to fetal anemia. Methods: The database was assessed to retrieve the ultrasound records of [...] Read more.
Objectives: To evaluate the diagnostic performance of CVPs in predicting fetal Hb Bart’s disease among pregnancies at risk and to study hemodynamic changes based on CVP components in response to fetal anemia. Methods: The database was assessed to retrieve the ultrasound records of fetuses at risk of Hb Bart’s disease at 17–22 weeks and the relevant files including complete video sets of fetal echocardiography. The five components of CVPs of each case were blindly assigned. The definitive diagnosis of fetal Hb Bart’s disease was based on cordocentesis or neonatal blood analysis. Results: Among 378 pregnancies at risk that were recruited into the study, there were 76 (20.1%) affected fetuses and 302 (79.9%) unaffected fetuses. Using a cut-off score of <9, CVPs had a sensitivity of 92.1% and specificity of 97.4% in predicting affected fetuses. However, the effectiveness was not much superior to cardio-thoracic area ratio (CTAR) alone (area under curve; AUC: 0.983 vs. 0.954). Of all parameters, CTAR provided the best diagnostic performance. The combination of CTAR and assessment of hydropic sign provided the best diagnostic values, comparable with full CVPs (AUC 0.982 vs. 0.983). The affected fetuses cope well with anemia by physically increasing in cardiac size and functionally increasing in Tei index with minimally reduced shortening fraction, without compromising arterial and venous Doppler indices. Conclusions: CVPs are highly effective in predicting affected fetuses among pregnancies at risk of fetal Hb Bart’s disease. Nevertheless, only two components (CTAR and hydropic sign) are adequate to yield the best diagnostic performance. Full article
(This article belongs to the Special Issue Advances in Fetal Cardiology)
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4 pages, 526 KB  
Interesting Images
Surgical Management of a Ruptured Giant Left Main Coronary Artery Aneurysm Presenting with Cardiac Tamponade
by Dmitriy Shumakov, Dmitriy Zybin, Elena Stepanova, Siarhei Dabravolski, Elena Sigaleva, Ekaterina Silina, Victor Stupin and Mikhail Popov
Diagnostics 2025, 15(18), 2302; https://doi.org/10.3390/diagnostics15182302 - 10 Sep 2025
Abstract
Coronary artery aneurysms (CAAs) are an uncommon finding, and their rupture is an exceedingly rare and life-threatening complication. Giant aneurysms of the left main coronary artery (LMCA) pose a significant diagnostic and therapeutic challenge. We describe the case of a 62-year-old male who [...] Read more.
Coronary artery aneurysms (CAAs) are an uncommon finding, and their rupture is an exceedingly rare and life-threatening complication. Giant aneurysms of the left main coronary artery (LMCA) pose a significant diagnostic and therapeutic challenge. We describe the case of a 62-year-old male who presented with acute coronary syndrome and was subsequently diagnosed with a ruptured giant LMCA aneurysm causing cardiac tamponade and multi-organ dysfunction. The initial diagnosis was suggested by coronary angiography and confirmed with contrast-enhanced multidetector computed tomography (MDCT) and echocardiography. The patient underwent emergency surgery consisting of aneurysm excision, thrombectomy, ligation of the LMCA ostium and its distal branches (LAD and circumflex), and coronary artery bypass grafting (CABG) using the left internal thoracic artery to the left anterior descending artery and a saphenous vein graft to a marginal branch. The patient’s postoperative course was complicated by transient multi-organ dysfunction, which resolved. He was discharged in a stable condition. This case highlights the critical importance of rapid multimodal imaging for diagnosis and the feasibility of emergency surgical intervention to achieve a favorable outcome in patients with a ruptured giant LMCA aneurysm. Full article
(This article belongs to the Collection Interesting Images)
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22 pages, 5732 KB  
Article
Explainable Transformer-Based Framework for Glaucoma Detection from Fundus Images Using Multi-Backbone Segmentation and vCDR-Based Classification
by Hind Alasmari, Ghada Amoudi and Hanan Alghamdi
Diagnostics 2025, 15(18), 2301; https://doi.org/10.3390/diagnostics15182301 - 10 Sep 2025
Abstract
Glaucoma is an eye disease caused by increased intraocular pressure (IOP) that affects the optic nerve head (ONH), leading to vision problems and irreversible blindness. Background/Objectives: Glaucoma is the second leading cause of blindness worldwide, and the number of people affected is [...] Read more.
Glaucoma is an eye disease caused by increased intraocular pressure (IOP) that affects the optic nerve head (ONH), leading to vision problems and irreversible blindness. Background/Objectives: Glaucoma is the second leading cause of blindness worldwide, and the number of people affected is increasing each year, with the number expected to reach 111.8 million by 2040. This escalating trend is alarming due to the lack of ophthalmology specialists relative to the population. This study proposes an explainable end-to-end pipeline for automated glaucoma diagnosis from fundus images. It also evaluates the performance of Vision Transformers (ViTs) relative to traditional CNN-based models. Methods: The proposed system uses three datasets: REFUGE, ORIGA, and G1020. It begins with YOLOv11 for object detection of the optic disc. Then, the optic disc (OD) and optic cup (OC) are segmented using U-Net with ResNet50, VGG16, and MobileNetV2 backbones, as well as MaskFormer with a Swin-Base backbone. Glaucoma is classified based on the vertical cup-to-disc ratio (vCDR). Results: MaskFormer outperforms all models in segmentation in all aspects, including IoU OD, IoU OC, DSC OD, and DSC OC, with scores of 88.29%, 91.09%, 93.83%, and 93.71%. For classification, it achieved accuracy and F1-scores of 84.03% and 84.56%. Conclusions: By relying on the interpretable features of the vCDR, the proposed framework enhances transparency and aligns well with the principles of explainable AI, thus offering a trustworthy solution for glaucoma screening. Our findings show that Vision Transformers offer a promising approach for achieving high segmentation performance with explainable, biomarker-driven diagnosis. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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22 pages, 518 KB  
Systematic Review
Governing Artificial Intelligence in Radiology: A Systematic Review of Ethical, Legal, and Regulatory Frameworks
by Faten M. Aldhafeeri
Diagnostics 2025, 15(18), 2300; https://doi.org/10.3390/diagnostics15182300 - 10 Sep 2025
Abstract
Purpose: This systematic review explores the ethical, legal, and regulatory frameworks governing the deployment of artificial intelligence technologies in radiology. It aims to identify key governance challenges and highlight strategies that promote the safe, transparent, and accountable integration of artificial intelligence in clinical [...] Read more.
Purpose: This systematic review explores the ethical, legal, and regulatory frameworks governing the deployment of artificial intelligence technologies in radiology. It aims to identify key governance challenges and highlight strategies that promote the safe, transparent, and accountable integration of artificial intelligence in clinical imaging. This review is intended for both medical practitioners and AI developers, offering clinicians a synthesis of ethical and legal considerations while providing developers with regulatory insights and guidance for future AI system design. Methods: A systematic review was conducted, examining thirty-eight peer-reviewed articles published between 2018 and 2025. Studies were identified through searches in PubMed, Scopus, and Embase using terms related to artificial intelligence, radiology, ethics, law, and regulation. The inclusion criteria focused on studies addressing governance implications, rather than technical design. A thematic content analysis was applied to identify common patterns and gaps across ethical, legal, and regulatory domains. Results: The findings reveal widespread radiology-specific concerns, including algorithmic bias in breast and chest imaging datasets, opacity in image-based AI systems such as pulmonary nodule detection models, and unresolved legal liability in cases where radiologists rely on FDA-cleared AI tools that fail to identify abnormalities. Regulatory frameworks vary significantly across regions with limited global harmonization, highlighting the need for adaptive oversight models and improved data governance. Conclusion: Responsible deployment of AI in radiology requires governance models that address bias, explainability, and medico-legal accountability while integrating ethical principles, legal safeguards, and adaptive oversight. This review provides tailored insights for medical practitioners, AI developers, policymakers, and researchers: clinicians gain guidance on ethical and legal responsibilities, developers on regulatory and design priorities, policymakers (especially in the Middle East) on regional framework gaps, and researchers on future directions. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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26 pages, 11216 KB  
Case Report
Clinicopathological Pearls and Diagnostic Pitfalls in IgG4-Related Disease: Challenging Case Series and Literature Review
by Sokol Sina, Giulio Luigi Bonisoli, Sofia Vitale, Luigi Marzano, Stefano Francesco Crinò, Maria Cristina Conti Bellocchi, Sara Boninsegna, Simone Conci, Federica Maiolini, Riccardo Nocini, Luca Sacchetto, Giorgio Barbera, Andrea Fior, Nikela Kalaja, Elena Malloggi, Antonietta Brighenti, Alice Parisi, Nicolò Cardobi, Aldo Scarpa, Simonetta Friso and Elisa Tinazziadd Show full author list remove Hide full author list
Diagnostics 2025, 15(18), 2299; https://doi.org/10.3390/diagnostics15182299 - 10 Sep 2025
Abstract
Background: IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Classic forms, such as pancreaticobiliary or retroperitoneal involvement, are often recognized early, whereas atypical manifestations mimic [...] Read more.
Background: IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Classic forms, such as pancreaticobiliary or retroperitoneal involvement, are often recognized early, whereas atypical manifestations mimic malignancy or inflammatory conditions, leading to delayed or inappropriate treatment. Case Series: A 30-year-old man presented with hyperemesis, proptosis, and gait instability. He was found to have colonic stenosis, stomach thickening, pachymeningitis, and polyserositis. Gastroenteric histology and serology confirmed IgG4-RD. Steroids were ineffective, but rituximab produced sustained clinical and radiologic improvement. A 35-year-old woman developed jaundice and cholestasis with a perihilar mass highly suggestive of cholangiocarcinoma. Histopathology revealed IgG4-RD, and rituximab therapy led to marked clinical and serological improvement. A 64-year-old woman with a submandibular mass underwent sialoadenectomy, with histology confirming IgG4-RD; she remained asymptomatic without systemic treatment. Literature Review: A literature review highlighted the diagnostic challenges of atypical IgG4-RD. Gastrointestinal involvement is rare and often misclassified as inflammatory bowel disease. Isolated biliary disease frequently mimics cholangiocarcinoma, while salivary gland involvement may be misdiagnosed as neoplasia. Serum IgG4 levels >135 mg/dL and IgG4/IgG ratio >0.21 may support clinical suspicion, but histopathology remains indispensable for definitive diagnosis and for excluding malignancy. Steroid responsiveness is a hallmark, though relapses after tapering are common, often necessitating B-cell-directed therapy. Conclusions: IgG4-RD should be considered in patients with unexplained, relapsing, or steroid-responsive conditions. Early recognition, multidisciplinary collaboration, and integration of histopathology with clinical features are essential to avoid misdiagnosis and optimize management. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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18 pages, 1552 KB  
Article
Comparative Evaluation of 24 LDL-C Estimation Equations Against Direct Assays in Two Independent Cohorts
by Imola Györfi, Oana Roxana Oprea, Ion Bogdan Mănescu, Antoanela Curici and Minodora Dobreanu
Diagnostics 2025, 15(18), 2298; https://doi.org/10.3390/diagnostics15182298 - 10 Sep 2025
Abstract
Background: Low-density lipoprotein cholesterol (LDL-C) is essential in diagnosing and managing dyslipidemias. While direct assays are faster than the reference beta-quantification method, many labs continue using the Friedewald (FW) equation, despite its limitations. Methods: Two large datasets were analyzed: 10,174 hospital samples (Cobas/Roche) [...] Read more.
Background: Low-density lipoprotein cholesterol (LDL-C) is essential in diagnosing and managing dyslipidemias. While direct assays are faster than the reference beta-quantification method, many labs continue using the Friedewald (FW) equation, despite its limitations. Methods: Two large datasets were analyzed: 10,174 hospital samples (Cobas/Roche) and 21,091 private lab samples (Alinity/Abbott). Various literature-based LDL-C equations were compared, focusing on FW, Sampson (SN), and Martin–Hopkins (MH). Direct LDL-C served as the reference. Evaluation metrics included bias and classification accuracy. Results: In samples with triglycerides < 400 mg/dL, several lesser-known equations showed acceptable bias (±5%), outperforming FW, SN, and MH, which had biases from −7.4% to −4.9%. Classification accuracy was higher with equations like Vujovic (up to 82.5%), compared to FW (65.8%), SN (73.1%), and MH (72.4%). The Vujovic equation showed minimal bias across triglyceride levels and the highest net gain in correct classification (3.4% and 1.57%). Conclusions: Multiple lesser-known LDL-C formulas outperformed widely used ones. The Vujovic equation yielded the best results, but the limited net clinical improvement suggests that replacing Friedewald may not be urgently necessary. Full article
(This article belongs to the Special Issue Exploring the Role of Diagnostic Biochemistry, 2nd Edition)
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12 pages, 714 KB  
Article
Assessment of Preprocedural Factors Associated with 5-Year Complete Response After Transarterial Radioembolization in Patients with Hepatocellular Carcinoma
by June Park, Dong Kyu Kim, Seungsoo Lee and Shin Hye Hwang
Diagnostics 2025, 15(18), 2297; https://doi.org/10.3390/diagnostics15182297 - 10 Sep 2025
Abstract
Background: There is little evidence available regarding the long-term tumor response after transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC). Aim: To identify preprocedural predictive factors for achieving a 5-year complete response (CR) following TARE in patients with HCC. Methods: This [...] Read more.
Background: There is little evidence available regarding the long-term tumor response after transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC). Aim: To identify preprocedural predictive factors for achieving a 5-year complete response (CR) following TARE in patients with HCC. Methods: This retrospective study included 37 patients with treatment-naïve HCC who underwent TARE between January 2016 and December 2019 and were followed for at least 5 years. Tumor characteristics—including maximum diameter, number of main lesions, presence of satellite nodules, and portal vein thrombosis—were evaluated using preprocedural liver dynamic magnetic resonance imaging. Treatment response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Multivariate logistic regression analyses were performed to identify factors associated with tumor response following TARE. Results: Thirty-seven patients (median age, 64 years) were categorized into two groups: (1) the CR group (n = 9), consisting of patients without tumor recurrence for 5 years and without additional treatment; and (2) the non-CR group (n = 28), consisting of patients who required additional treatment because of residual or recurrent viable tumors. Tumors in the non-CR group had significantly larger diameters compared with those in the CR group (9.8 cm vs. 5.9 cm, p = 0.006). In multivariable analysis, a tumor diameter > 7 cm was the only factor significantly associated with tumor recurrence (odds ratio = 21.277, p = 0.010). Portal vein thrombosis did not reach statistical significance (odds ratio = 9.779, p = 0.063). Conclusions: Tumor diameter > 7 cm is a significant predictor of tumor recurrence within 5 years after TARE for HCC. This finding may support a more individualized post-TARE management approach, potentially allowing clinicians to avoid overtreatment and adopt a watchful waiting strategy for selected patients. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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22 pages, 5732 KB  
Article
Autoantibody Profiling for Accurate Differentiation of Type 1 and Type 2 Diabetes Mellitus in Omani Patients: A Retrospective Study
by Souad Al-Okla, Salima Al Maqbali, Hamdi Al Mutori, Amna Mohammed Al-Hinai, Rayyan Hassan Al Bloushi, Mallak Ahmed Aljabri, Haya Nasser Alsenani and Mohammad Al Shafaee
Diagnostics 2025, 15(18), 2296; https://doi.org/10.3390/diagnostics15182296 - 10 Sep 2025
Abstract
Background/Objectives: Differentiating Type 1 from Type 2 diabetes mellitus (T1DM vs. T2DM) remains clinically challenging, especially in early-onset cases with overlapping features. This study assessed the diagnostic utility of diabetes-related autoantibodies in an Omani cohort and evaluated their predictive performance using machine learning. [...] Read more.
Background/Objectives: Differentiating Type 1 from Type 2 diabetes mellitus (T1DM vs. T2DM) remains clinically challenging, especially in early-onset cases with overlapping features. This study assessed the diagnostic utility of diabetes-related autoantibodies in an Omani cohort and evaluated their predictive performance using machine learning. Methods: Clinical and laboratory data from 448 patients (aged ≥ 2 years) in Al Batinah North, Oman, were retrospectively analyzed. We assessed autoantibody positivity (anti-GAD, anti-islet, anti-TPO, anti-tissue), age, sex, and HbA1c. Receiver operating characteristic (ROC) curves and a neural network model were used to evaluate diagnostic accuracy. Results: Anti-GAD and anti-islet antibodies were significantly more prevalent in T1DM (69.0% and 64.1%) than T2DM (7.4% and 3.8%; p < 0.0001). HbA1c was elevated in both subtypes but lacked discriminatory specificity. Nearly half (48.5%) of T1DM patients showed multiple antibody positivity, especially in younger age groups. Anti-TPO and anti-tissue antibodies were more frequently detected in T1DM, suggesting broader autoimmunity. ROC analysis showed strong predictive value for anti-islet (AUC = 0.835) and anti-GAD (AUC = 0.827). Neural network modeling identified anti-GAD, anti-islet, and age as the most informative predictors, achieving over 92% classification accuracy. Importantly, antibody positivity in a subset of insulin-treated T2DM patients suggested potential latent autoimmune diabetes (LADA) misclassification. Conclusions: This is the first study in Oman to combine autoantibody screening with AI-based modeling to refine diabetes classification. Our findings highlight the value of immunological profiling in early diagnosis, uncover possible misclassification, and support AI integration to guide individualized management. Full article
(This article belongs to the Special Issue Advances in Modern Diabetes Diagnosis and Treatment Technology)
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21 pages, 1247 KB  
Review
Bayesian Graphical Models for Multiscale Inference in Medical Image-Based Joint Degeneration Analysis
by Rahul Kumar, Kiran Marla, Puja Ravi, Kyle Sporn, Rohit Srinivas, Swapna Vaja, Alex Ngo and Alireza Tavakkoli
Diagnostics 2025, 15(18), 2295; https://doi.org/10.3390/diagnostics15182295 - 10 Sep 2025
Abstract
Joint degeneration is a major global health issue requiring improved diagnostic and prognostic tools. This review examines whether integrating Bayesian graphical models with multiscale medical imaging can enhance detection, analysis, and prediction of joint degeneration compared to traditional single-scale methods. Recent advances in [...] Read more.
Joint degeneration is a major global health issue requiring improved diagnostic and prognostic tools. This review examines whether integrating Bayesian graphical models with multiscale medical imaging can enhance detection, analysis, and prediction of joint degeneration compared to traditional single-scale methods. Recent advances in quantitative MRI, such as T2 mapping, enable early detection of subtle cartilage changes, supporting earlier intervention. Bayesian graphical models provide a flexible framework for representing complex relationships and updating predictions as new evidence emerges. Unlike prior reviews that address Bayesian methods or musculoskeletal imaging separately, this work synthesizes these domains into a unified framework that spans molecular, cellular, tissue, and organ-level analyses, providing methodological guidance and clinical translation pathways. Key topics within Bayesian inference include multiscale analysis, probabilistic graphical models, spatial-temporal modeling, network connectivity analysis, advanced imaging biomarkers, quantitative analysis, quantitative MRI techniques, radiomics and texture analysis, multimodal integration strategies, uncertainty quantification, variational inference approaches, Monte Carlo methods, and model selection and validation, as well as diffusion models for medical imaging and Bayesian joint diffusion models. Additional attention is given to diffusion models for advanced medical image generation, addressing challenges such as limited datasets and patient privacy. Clinical translation and validation requirements are emphasized, highlighting the need for rigorous evaluation to ensure that synthesized or processed images maintain diagnostic accuracy. Finally, this review discusses implementation challenges and outlines future research directions, emphasizing the potential for earlier diagnosis, improved risk assessment, and personalized treatment strategies to reduce the growing global burden of musculoskeletal disorders. Full article
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16 pages, 1848 KB  
Article
Optimization of DNA Fragmentation Techniques to Maximize Coverage Uniformity of Clinically Relevant Genes Using Whole Genome Sequencing
by Vanessa Process, Madana M.R. Ambavaram, Sameer Vasantgadkar, Sushant Khanal, Martina Werner, Maura A. Berkeley, Zachary T. Herbert, Greg Endress, Ulrich Thomann and Eugenio Daviso
Diagnostics 2025, 15(18), 2294; https://doi.org/10.3390/diagnostics15182294 - 10 Sep 2025
Abstract
Background: Coverage uniformity is pivotal in whole genome sequencing (WGS), as uneven read distributions can obscure clinically relevant variants and compromise downstream analyses. While enzyme-based fragmentation methods for WGS library preparation are widely used, they can introduce sequence-specific biases that disproportionately affect high-GC [...] Read more.
Background: Coverage uniformity is pivotal in whole genome sequencing (WGS), as uneven read distributions can obscure clinically relevant variants and compromise downstream analyses. While enzyme-based fragmentation methods for WGS library preparation are widely used, they can introduce sequence-specific biases that disproportionately affect high-GC or low-GC regions. Here, we compare four PCR-free WGS library preparation workflows—one employing mechanical fragmentation and three based on enzymatic fragmentation—to assess their impact on coverage uniformity and variant detection. Results: Libraries were generated with Coriell NA12878 and DNA isolated from DNA blood, saliva, and formalin-fixed paraffin-embedded (FFPE) samples. Sequencing was performed on an Illumina NovaSeq 6000, followed by alignment to the human reference genome (GRCh38/hg38) and local realignment. We assessed coverage at both chromosomal and gene levels, including 504 clinically relevant genes detected in the TruSight™ Oncology 500 (TSO500) panel. Additionally, we examined the relationship between GC content and normalized coverage, as well as variant detection across high- and low-GC regions. Conclusions: Our findings show that mechanical fragmentation yields a more uniform coverage profile across different sample types and across the GC spectrum. Enzymatic workflows, on the other hand, demonstrated more pronounced coverage imbalances, particularly in high-GC regions, potentially affecting the sensitivity of variant detection. This effect was evident in analyses focusing on the TSO500 gene set, where uniform coverage is critical for accurate identification of disease-associated variants and for minimizing false negatives. Downsampling experiments further revealed that mechanical fragmentation maintained lower Single Nucleotide Polymorphism (SNPs) false-negative and false-positive rates at reduced sequencing depths, thereby highlighting the advantages of consistent coverage for resource-efficient WGS. This study introduces a novel framework for evaluating WGS coverage uniformity, providing guidance for optimizing library preparation protocols in clinical and translational research. By quantifying how fragmentation strategies influence coverage depth and variant calling accuracy, laboratories can refine their sequencing workflows to ensure more reliable detection of clinically actionable variants—especially in high-GC regions often implicated in hereditary disease and oncology. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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15 pages, 1728 KB  
Article
The Utility of Mesenteric T1 Mapping on MR Enterography in Crohn’s Disease: A Preliminary Study
by Seongkeun Park, Jieun Byun and Youe Ree Kim
Diagnostics 2025, 15(18), 2293; https://doi.org/10.3390/diagnostics15182293 - 10 Sep 2025
Abstract
Background: Crohn’s disease (CD) is a chronic disorder characterized by transmural bowel wall involvement and mesenteric changes, including inflammation and fibrosis. Although Magnetic Resonance Imaging (MRI)-based scoring systems have been proposed for the quantitative assessment of bowel wall changes in Magnetic Resonance enterography [...] Read more.
Background: Crohn’s disease (CD) is a chronic disorder characterized by transmural bowel wall involvement and mesenteric changes, including inflammation and fibrosis. Although Magnetic Resonance Imaging (MRI)-based scoring systems have been proposed for the quantitative assessment of bowel wall changes in Magnetic Resonance enterography (MRE), there has been limited discussion regarding methods for the quantitative evaluation of mesenteric involvement. T1 mapping is an emerging MRI technique, potentially reflecting inflammation and fibrosis. This study aimed to assess the clinical utility of mesenteric T1 mapping in patients with CD. Methods: We retrospectively analyzed 71 adults with CD who underwent MRE from October 2024 to May 2025. Mesenteric native T1, post-contrast T1 relaxation times, their difference (ΔT1), and the extracellular volume (ECV) fraction were measured. Regions of interest were placed in mesenteric tissue adjacent to affected bowel segments, avoiding lymph nodes and artifacts. The Crohn’s Disease Activity Index (CDAI) was used to classify disease activity. Group differences and correlations with CDAI were evaluated. Results: Native T1 values were significantly higher in active CD than inactive disease (414.3 ms vs. 355.2 ms, p < 0.001). ΔT1 was also elevated in active disease (122.5 ms vs. 55.9 ms, p < 0.001), while post-contrast T1 and ECV did not differ significantly. Native T1 and ΔT1 showed significant positive correlations with CDAI (r = 0.53 and r = 0.46, respectively), while ECV had a weaker correlation (r = 0.27, p = 0.025). Conclusions: Mesenteric T1 mapping shows potential as a non-invasive biomarker of mesenteric involvement in CD. With further validation, mesenteric T1 mapping could enable more comprehensive disease assessment and improve the accuracy of clinical characterization in patients with Crohn’s disease. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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12 pages, 1321 KB  
Article
Evaluation of CK8/18 and CK19 Expression as Adjunct Immunohistochemical Markers in Non-Keratinizing Nasopharyngeal Carcinoma
by Ummul Afila Omar, Suria Hayati Binti Md Pauzi, Mohd Razif Bin Mohamad Yunus, Rosnah Sutan, Nur Maya Sabrina binti Tizen Laim, Muaatamarulain bin Mustangin and Reena Rahayu Md Zin
Diagnostics 2025, 15(18), 2292; https://doi.org/10.3390/diagnostics15182292 - 10 Sep 2025
Abstract
Background: Nasopharyngeal carcinoma (NPC), particularly the non-keratinizing subtype (NK-NPC), is prevalent in Southeast Asia and often presents diagnostic challenges due to overlapping histological features with benign nasopharyngeal lesions. While Epstein–Barr virus (EBV) serology supports diagnosis in many cases, its limitations in sensitivity and [...] Read more.
Background: Nasopharyngeal carcinoma (NPC), particularly the non-keratinizing subtype (NK-NPC), is prevalent in Southeast Asia and often presents diagnostic challenges due to overlapping histological features with benign nasopharyngeal lesions. While Epstein–Barr virus (EBV) serology supports diagnosis in many cases, its limitations in sensitivity and specificity necessitate additional tissue-based markers. Objective: To assess the immunohistochemical expression of cytokeratins CK8/18 and CK19 in NPC compared to benign nasal tissue and evaluate their potential as adjunct immunohistochemical markers. Methods: This retrospective study evaluated the immunohistochemical expression of cytokeratins CK8/18 and CK19 in 24 NK-NPC and 22 benign nasopharyngeal tissue samples collected between April 2021 and April 2024 at Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia. Staining intensity and distribution were scored semi-quantitatively, and statistical analysis was performed using SPSS v29.0 (p < 0.05). Results: CK19 was expressed in all NK-NPC cases, with strong positivity in 79.2%, while CK8/18 was positive in 92%, primarily with weak to moderate staining. Only one benign case (inverted papilloma) showed focal positivity. The differences in expression between malignant and benign tissues were statistically significant (p < 0.001). Sub-analysis of EBER-positive cases (n = 15) confirmed consistently strong CK19 expression. Conclusions: Based on this small retrospective cohort, CK8/18 and particularly CK19 demonstrate expression patterns that may support their use as adjunct immunohistochemical markers in the histopathological assessment of NK-NPC, especially in morphologically ambiguous cases. Further validation in larger studies is needed before these markers can be considered for routine diagnostic application. Full article
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16 pages, 1094 KB  
Article
Recognition of EEG Features in Autism Disorder Using SWT and Fisher Linear Discriminant Analysis
by Fahmi Fahmi, Melinda Melinda, Prima Dewi Purnamasari, Elizar Elizar and Aufa Rafiki
Diagnostics 2025, 15(18), 2291; https://doi.org/10.3390/diagnostics15182291 - 10 Sep 2025
Abstract
Background/Objectives: An ASD diagnosis from EEG is challenging due to non-stationary, low-SNR signals and small cohorts. We propose a compact, interpretable pipeline that pairs a shift-invariant Stationary Wavelet Transform (SWT) with Fisher’s Linear Discriminant (FLDA) as a supervised projection method, delivering band-level [...] Read more.
Background/Objectives: An ASD diagnosis from EEG is challenging due to non-stationary, low-SNR signals and small cohorts. We propose a compact, interpretable pipeline that pairs a shift-invariant Stationary Wavelet Transform (SWT) with Fisher’s Linear Discriminant (FLDA) as a supervised projection method, delivering band-level insight and subject-wise evaluation suitable for resource-constrained clinics. Methods: EEG from the KAU dataset (eight ASD, eight controls; 256 Hz) was decomposed with SWT (db4). We retained levels 3, 4, and 6 (γ/β/θ) as features. FLDA learned a low-dimensional discriminant subspace, followed by a linear decision rule. Evaluation was conducted using a subject-wise 70/30 split (no subject overlap) with accuracy, precision, recall, F1, and confusion matrices. Results: The β band (Level 4) achieved the best performance (accuracy/precision/recall/F1 = 0.95), followed by γ (0.92) and θ (0.85). Despite partial overlap in FLDA scores, the projection maximized between-class separation relative to within-class variance, yielding robust linear decisions. Conclusions: Unlike earlier FLDA-only pipelines and wavelet–entropy–ANN approaches, our study (1) employs SWT (undecimated, shift-invariant) rather than DWT to stabilize sub-band features on short resting segments, (2) uses FLDA as a supervised projection to mitigate small-sample covariance pathologies before classification, (3) provides band-specific discriminative insight (β > γ/θ) under a subject-wise protocol, and (4) targets low-compute deployment. These choices yield a reproducible baseline with competitive accuracy and clear clinical interpretability. Future work will benchmark kernel/regularized discriminants and lightweight deep models as cohort size and compute permit. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—3rd Edition)
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14 pages, 954 KB  
Article
A YOLO Ensemble Framework for Detection of Barrett’s Esophagus Lesions in Endoscopic Images
by Wan-Chih Lin, Chi-Chih Wang, Ming-Chang Tsai, Chao-Yen Huang, Chun-Che Lin and Ming-Hseng Tseng
Diagnostics 2025, 15(18), 2290; https://doi.org/10.3390/diagnostics15182290 - 10 Sep 2025
Abstract
Background and Objectives: Barrett’s Esophagus (BE) is a precursor to esophageal adenocarcinoma, and early detection is essential to reduce cancer risk. This study aims to develop a YOLO-based ensemble framework to improve the automated detection of BE-associated mucosal lesions on endoscopic images. [...] Read more.
Background and Objectives: Barrett’s Esophagus (BE) is a precursor to esophageal adenocarcinoma, and early detection is essential to reduce cancer risk. This study aims to develop a YOLO-based ensemble framework to improve the automated detection of BE-associated mucosal lesions on endoscopic images. Methods: A dataset of 3620 annotated endoscopic images was collected from 132 patients. Five YOLO variants, YOLOv5, YOLOv9, YOLOv10, YOLOv11, and YOLOv12, were selected based on their architectural diversity and detection capabilities. Each model was trained individually, and their outputs were integrated using a Non-Maximum Suppression (NMS)-based ensemble strategy. Multiple ensemble configurations were evaluated to assess the impact of fusion depth on detection performance. Results: The ensemble models consistently outperformed individual YOLO variants in recall, the primary evaluation metric. The entire five-model ensemble achieved the highest recall (0.974), significantly reducing missed lesion detections. Statistical analysis using McNemar’s test and bootstrap confidence intervals confirmed the superiority in most comparisons. Conclusions: The proposed YOLO ensemble framework demonstrates enhanced sensitivity and robustness in detecting BE lesions. Its integration into clinical workflows can improve early diagnosis and reduce diagnostic workload, offering a promising tool for computer-aided screening in gastroenterology. Full article
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14 pages, 2948 KB  
Case Report
NUAK2 Pathogenic Variants Are Definitively Associated with Neural Tube Defects in Humans: New Genotype-Phenotype Correlation and Review of the Literature
by Gioia Mastromoro, Claudio Dello Russo, Stefania Mariani, Serena Bucossi, Riccardo Riccardi, Amit Pal, Rosanna Squitti, Mehak Dangi, Antonio Pizzuti and Mauro Ciro Antonio Rongioletti
Diagnostics 2025, 15(18), 2289; https://doi.org/10.3390/diagnostics15182289 - 10 Sep 2025
Abstract
Background and Clinical Significance: Neural tube defects (NTDs) represent a group of malformations, typically arising from a complex interplay between genetic susceptibility and environmental influences. Increasing evidence points to the contribution of rare pathogenic variants in genes involved in embryonic development in selected [...] Read more.
Background and Clinical Significance: Neural tube defects (NTDs) represent a group of malformations, typically arising from a complex interplay between genetic susceptibility and environmental influences. Increasing evidence points to the contribution of rare pathogenic variants in genes involved in embryonic development in selected cases. To date, two families with NTDs carrying biallelic variants in TRIM36 and NUAK2 have been described. Specifically, germline homozygous pathogenic variants in NUAK2 were identified in three fetuses with anencephaly, thus implicating this gene as a critical regulator of neural tube closure. Case Presentation: We describe a family in which five individuals presented with sacral dimples, a subtle midline defect considered a minor malformation. Exome sequencing revealed a heterozygous missense variant, c.487G>A in NUAK2, segregating with the phenotype. Although sacral dimples are often clinically silent and do not typically cause functional impairment, their presence in multiple relatives highlights a possible shared genetic etiology. Careful phenotypic recognition of such findings can therefore provide valuable insights into underlying molecular mechanisms. Conclusions: This report extends the clinical spectrum of NUAK2-related anomalies by demonstrating a novel genotype–phenotype correlation. Our findings suggest that variants in this gene may follow a semi-dominant inheritance pattern, with heterozygous carriers manifesting milder phenotypes, such as sacral dimples, while biallelic pathogenic variants lead to severe NTDs. This observation reinforces the association between NUAK2 loss-of-function variants and NTDs and emphasizes the importance of genetic investigations in families where such dysmorphic traits recur. Ultimately, these results contribute to clarifying the molecular basis of NTDs and may inform both genetic counseling and risk stratification in affected families. Full article
(This article belongs to the Special Issue Prenatal Diagnosis: From Morphological Evaluation to Genetic Testing)
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15 pages, 2063 KB  
Systematic Review
Metformin and Risk of New-Onset Atrial Fibrillation in Type 2 Diabetes: A Systematic Review and Meta-Analysis
by Roopeessh Vempati, Nanush Damarlapally, Poulami Roy, Maneeth Mylavarapu, Srivatsa Surya Vasudevan, Reshma Reguram, Tanisha Vora, Hritvik Jain, Raheel Ahmed and Geetha Krishnamoorthy
Diagnostics 2025, 15(18), 2288; https://doi.org/10.3390/diagnostics15182288 - 10 Sep 2025
Abstract
Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, increasingly prevalent worldwide. Type 2 diabetes mellitus (T2DM) is a major chronic disorder and a significant risk factor for AF, contributing to high morbidity and mortality. Metformin monotherapy can contribute to the [...] Read more.
Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, increasingly prevalent worldwide. Type 2 diabetes mellitus (T2DM) is a major chronic disorder and a significant risk factor for AF, contributing to high morbidity and mortality. Metformin monotherapy can contribute to the reduced occurrence of adverse cardiovascular outcomes in patients with T2DM, but its effects on AF are understudied. This meta-analysis evaluates the association of metformin with the risk of incident AF among patients with T2DM on metformin. Methods: Databases, including PubMed, Google Scholar, and EMBASE, were screened through November 2024 for studies evaluating the association between metformin and new-onset AF in patients with T2DM. Comprehensive Meta-Analysis (CMA) version 4, by Biostat, Inc., utilizing a random effects model, was used to pool hazard ratios (HR) and 95% confidence intervals (CI). A meta-regression analysis was also performed to identify factors that may have influenced the results. A p-value < 0.05 was considered statistically significant. Results: A total of seven studies, comprising 4,017,929 patients with T2DM, having a mean age of 62.82 years and 52.5% males, were included. Metformin was associated with a statistically significantly lower risk of new-onset AF among patients with T2DM compared to other hypoglycemic agents (aHR: 0.85; 95% CI 0.76–0.94; p = 0.002). Meta-regression analysis identified age as a significant moderator of the treatment effect (β = −3.15, p = 0.001). Conclusions: Metformin is associated with a lower risk of new-onset AF among patients with T2DM compared to other hypoglycemic agents. Furthermore, age-related attenuation of this association was observed, with older patients with T2DM showing a weaker association. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Management in Cardiology)
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19 pages, 1730 KB  
Article
Stroke in Dilated Cardiomyopathy: An Autopsy-Based Study of Mechanisms, Topography, and Clinical Implications
by Otilia Țica, Monica Sabău, Alina Venter, Corina Beiușanu, Mihail Berechet, Anca Huniadi, Mircea Ioan Șandor and Ovidiu Țica
Diagnostics 2025, 15(18), 2287; https://doi.org/10.3390/diagnostics15182287 - 9 Sep 2025
Abstract
Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and arrhythmic mortality; yet, its association with cerebrovascular events, particularly in the absence of atrial fibrillation (AF), remains insufficiently explored. Purpose: This study aimed to determine the prevalence, mechanisms, and anatomical distribution [...] Read more.
Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and arrhythmic mortality; yet, its association with cerebrovascular events, particularly in the absence of atrial fibrillation (AF), remains insufficiently explored. Purpose: This study aimed to determine the prevalence, mechanisms, and anatomical distribution of stroke in patients with DCM and to assess the role of AF and structural remodeling in stroke risk. Methods: We retrospectively analyzed 471 patients who died with DCM at the Emergency County Clinical Hospital of Bihor between 1 January 2022 and 31 December 2024. Clinical records, neuroimaging, autopsy reports, and histopathological data were reviewed. Stroke subtypes were classified according to TOAST criteria (large artery atherosclerosis, cardioembolic, small vessel disease, other determined, undetermined) and hemorrhagic categories (intracerebral, subarachnoid). Demographic, echocardiographic, and comorbidity data were compared between patients with and without cerebrovascular events. Results: Of 471 patients with DCM, 45 (9.6%) had concomitant stroke: pure ischemic in 32 (71.1%), 7 (15.6%) showed ischemic with hemorrhagic transformation, and primary hemorrhagic in 6 (13.3%). The parietal lobe was most frequently affected. AF was present in 26 patients (57.8%) and was significantly associated with ischemic stroke (p = 0.004), though embolic strokes also occurred in sinus rhythm. Patients with stroke had significantly lower left ventricular ejection fraction (28.0 ± 13.7% vs. 34.0 ± 11.2%, p = 0.007) and larger atrial dimensions. Histopathological findings confirmed acute and chronic ischemic injury patterns, including “red neurons,” white matter vacuolization, and gliotic scarring. Conclusions: Stroke is a frequent and often underdiagnosed complication in DCM, predominantly ischemic and embolic in nature. Importantly, embolic events were observed even in patients without AF, suggesting that atrial remodeling in DCM may independently predispose to cerebrovascular risk. These results underscore the need for refined preventive strategies, including careful atrial assessment and exploration of whether anticoagulation may benefit selected high-risk DCM patients without AF, a question that requires confirmation in prospective trials. Potential embolic sources in DCM include atrial cardiopathy and left ventricular thrombus in the setting of severe systolic dysfunction; therefore, careful ventricular as well as atrial assessment is warranted in high-risk DCM. Full article
(This article belongs to the Special Issue Updates on Stroke: Diagnosis and Management)
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20 pages, 7066 KB  
Review
miRNA-Orchestrated Fibroinflammatory Responses in Heart Failure with Preserved Ejection Fraction: Translational Opportunities for Precision Medicine
by Maria Andreea Micu, Dan Alexandru Cozac and Alina Scridon
Diagnostics 2025, 15(18), 2286; https://doi.org/10.3390/diagnostics15182286 - 9 Sep 2025
Abstract
Heart failure with a preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases. It continues to impose a significant global cardiovascular burden due to its rising prevalence, complex pathophysiology, and limited treatment options. The absence of effective disease-modifying therapies [...] Read more.
Heart failure with a preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases. It continues to impose a significant global cardiovascular burden due to its rising prevalence, complex pathophysiology, and limited treatment options. The absence of effective disease-modifying therapies is primarily attributable to the complex and heterogeneous pathophysiology underlying HFpEF. The hallmark of HFpEF is systemic inflammation, mostly originating from extracardiac comorbidities, which initiates and sustains the process of myocardial fibrosis, resulting in diastolic dysfunction. Recent evidence has identified specific micro ribonucleic acids (miRNAs) as key regulatory molecules in this inflammation–fibrosis cascade. Particularly, miR-21 and miR-29 play a central role in modulating these pathological processes by regulating the post-transcriptional expression of genes involved in inflammation, cardiac fibrosis, and remodeling. The inflammation-fibrosis axis in HFpEF offers multiple therapeutic opportunities ranging from direct anti-fibrotic strategies to the modulation of inflammation and fibrosis-related miRNA signatures. Such targeted approaches, especially miRNA modulation, hold potential to disrupt fundamental molecular mechanisms driving disease progression, moving beyond conventional HFpEF management. This narrative review explores the roles of miRNAs in modulating inflammation and fibrosis in HFpEF, critically assesses their potential as diagnostic and prognostic biomarkers, and evaluates their therapeutic application. Given the urgent clinical need for efficient HFpEF treatment strategies, understanding miRNA-mediated regulation of the inflammation–fibrosis axis is essential for developing personalized, mechanism-based therapies for HFpEF that could fundamentally change the HFpEF management paradigm. Full article
(This article belongs to the Special Issue Biomarker-Guided Advances in Diagnostic Medicine)
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14 pages, 304 KB  
Review
The Evolving Landscape of microRNAs in Cholangiocarcinoma and Pancreatic Cancer
by Andrada Ozana Schneider, Sabrina Birsan, Paula Anderco, Cristian Ichim, Samuel Bogdan Todor, Horatiu Dura, Radu Fleacă and Adrian Boicean
Diagnostics 2025, 15(18), 2285; https://doi.org/10.3390/diagnostics15182285 - 9 Sep 2025
Abstract
Cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies with limited therapeutic options and poor prognoses. In recent years, microRNAs (miRNAs) have gained attention as key molecular regulators involved in tumor progression, chemoresistance, and metastasis. This review explores the diagnostic, prognostic, and [...] Read more.
Cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies with limited therapeutic options and poor prognoses. In recent years, microRNAs (miRNAs) have gained attention as key molecular regulators involved in tumor progression, chemoresistance, and metastasis. This review explores the diagnostic, prognostic, and therapeutic potential of miRNAs in CCA and PDAC, emphasizing their shared and distinct molecular pathways and their utility in the context of precision oncology. Several dysregulated miRNAs, most notably miR-21 and miR-155, are overexpressed in both cancers and contribute to activation of oncogenic pathways such as PI3K/AKT signaling, epithelial–mesenchymal transition, and inflammatory cascades. miR-21, in particular, is associated with resistance to gemcitabine and cisplatin. In contrast, tumor-suppressive miRNAs such as miR-34a and miR-145 are often downregulated, and their restoration using synthetic mimics has demonstrated promising antitumor effects in preclinical studies. Moreover, circulating miRNAs show potential as non-invasive biomarkers for early detection and disease monitoring. Advanced delivery platforms, including nanoparticles and exosome-based systems, are being developed to improve the stability and tumor specificity of miRNA-based therapeutics. miRNAs represent a promising class of molecules in the diagnosis, stratification, and treatment of CCA and PDAC. Their dual role as biomarkers and therapeutic agents positions them at the intersection of molecular pathology and personalized medicine. Further multicenter clinical trials and mechanistic studies are needed to validate their clinical applicability and to refine delivery strategies for targeted miRNA modulation. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
13 pages, 807 KB  
Article
Low Preoperative Cachexia Index Is Associated with Severe Postoperative Morbidity in Patients Undergoing Gastrectomy for Gastric Cancer
by Melih Can Gül, Muhammet Kadri Çolakoğlu, Volkan Öter, Neslihan Karaca, Sadettin Emre Eroğlu, Rıza Sarper Ökten and Erdal Birol Bostancı
Diagnostics 2025, 15(18), 2284; https://doi.org/10.3390/diagnostics15182284 - 9 Sep 2025
Abstract
Background/Objective: Cancer cachexia is a multifactorial syndrome that contributes to adverse surgical outcomes in gastric cancer (GC), yet weight-based criteria often fail to detect subclinical cases. This study aimed to assess the prognostic utility of the Cancer Cachexia Index (CXI) in predicting [...] Read more.
Background/Objective: Cancer cachexia is a multifactorial syndrome that contributes to adverse surgical outcomes in gastric cancer (GC), yet weight-based criteria often fail to detect subclinical cases. This study aimed to assess the prognostic utility of the Cancer Cachexia Index (CXI) in predicting severe postoperative complications after curative gastrectomy. Methods: We retrospectively analyzed 301 patients with GC who underwent curative surgery between January 2020 and October 2023. CXI was calculated as L3 skeletal muscle index × serum albumin/neutrophil-to-lymphocyte ratio (NLR), and patients were stratified into low- and high-CXI groups based on sex-specific medians. Postoperative complications were classified using Clavien–Dindo, with grade ≥ III considered major morbidity. Group comparisons included rates of major complications and hospital stay. Results: The low-CXI group had significantly lower muscle mass and albumin levels, higher inflammatory markers, and more T4 tumors. Major complications occurred more frequently in this group (p < 0.001). In multivariate logistic regression, low CXI independently predicted severe complications (OR: 2.89; 95% CI: 1.42–5.85; p = 0.003), alongside older age and smoking. Receiver operating characteristic (ROC) analysis showed a CXI cut-off of 34.75 yielded high specificity (94.86%) for predicting major morbidity. Conclusions: Preoperative CXI is an effective predictor of severe postoperative morbidity in GC patients, outperforming traditional nutritional and inflammatory markers. Incorporation of CXI into routine preoperative assessment may enhance surgical risk stratification and guide perioperative optimization. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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