Diagnostics

4 pages, 789 KB

Open AccessInteresting Images

Ocular Involvement in a Pediatric Patient with Geleophysic Dysplasia

by Bogumiła Wójcik-Niklewska, Zofia Oliwa, Paulina Sawuła and Adrian Smędowski

Diagnostics 2026, 16(2), 193; https://doi.org/10.3390/diagnostics16020193 - 7 Jan 2026

Geleophysic dysplasia (GD) is a rare genetic skeletal disorder belonging to the acromelic group, characterized by short stature, distinctive facial features, thickened skin, and progressive cardiac involvement. We report a case of a 3-year-old boy with GD caused by a heterozygous c.5198G>A variant [...] Read more.

Geleophysic dysplasia (GD) is a rare genetic skeletal disorder belonging to the acromelic group, characterized by short stature, distinctive facial features, thickened skin, and progressive cardiac involvement. We report a case of a 3-year-old boy with GD caused by a heterozygous c.5198G>A variant in the FBN1 gene, presenting with ocular abnormalities. The patient demonstrated coarse facial features, short hands and feet, and a history of mitral valve stenosis requiring mechanical valve replacement. He was referred to the ophthalmology department for evaluation of left eye strabismus and elevated intraocular pressure. Fundus examination revealed a pink optic disc with blurred margins, slightly elevated above the retinal plane, absent foveal reflex, and tortuous vessels, consistent with optic disc drusen on ocular ultrasonography. Photopic negative response (PhNR) testing showed markedly reduced amplitudes in both eyes, indicating retinal ganglion cell dysfunction. Pattern VEP revealed normal P100 latencies in both eyes, with a 30% reduction in amplitude in the left eye, likely related to poorer fixation. This case highlights optic disc drusen and retinal ganglion cell dysfunction as potential ocular manifestations of geleophysic dysplasia, emphasizing the need for comprehensive ophthalmologic evaluation in affected patients. Full article

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

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14 pages, 3240 KB

Open AccessReview

Ten Questions on Using Lung Ultrasonography to Diagnose and Manage Pneumonia in Hospital-at-Home Model: Part III—Synchronicity and Foresight

by Nin-Chieh Hsu, Yu-Feng Lin, Hung-Bin Tsai, Charles Liao and Chia-Hao Hsu

Diagnostics 2026, 16(2), 192; https://doi.org/10.3390/diagnostics16020192 - 7 Jan 2026

Abstract

The hospital-at-home (HaH) model delivers hospital-level care to patients in their homes, with point-of-care ultrasonography (PoCUS) serving as a cornerstone diagnostic tool for respiratory illnesses such as pneumonia. This review—the third in a series—addresses the prognostic, synchronous, and potential overdiagnostic concerns of lung [...] Read more.

The hospital-at-home (HaH) model delivers hospital-level care to patients in their homes, with point-of-care ultrasonography (PoCUS) serving as a cornerstone diagnostic tool for respiratory illnesses such as pneumonia. This review—the third in a series—addresses the prognostic, synchronous, and potential overdiagnostic concerns of lung ultrasound (LUS) in managing pneumonia within HaH settings. LUS offers advantages of safety and repeatability, allowing clinicians to identify “red flag” sonographic findings that signal complicated or severe disease, including pleural line abnormalities, fluid bronchograms, absent Doppler perfusion, or poor diaphragmatic motion. Serial LUS examinations correlate closely with clinical recovery, showing progressive resolution of consolidations, B-lines, and pleural effusions, and thus provide a non-invasive method for monitoring therapeutic response. Compared with chest radiography, LUS demonstrates superior sensitivity in detecting pneumonia, pleural effusion, and interstitial syndromes across pediatric and adult populations. However, specificity may decline in tuberculosis-endemic or obese populations due to technical limitations and overlapping imaging patterns. Overdiagnosis remains a concern, as highly sensitive ultrasonography may identify minor or clinically irrelevant lesions, potentially leading to overtreatment. To mitigate this, PoCUS should be applied in parallel with conventional diagnostics and integrated into comprehensive clinical assessment. Standardized training, multi-zone scanning protocols, and structured image acquisition are recommended to improve reproducibility and inter-operator consistency. Full article

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

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12 pages, 1137 KB

Open AccessPerspective

Reframing Cervical Insufficiency as a Dynamic Process in the Preterm Birth Continuum: From Fixed Disease to a Modifiable Condition

by Moon-Il Park

Diagnostics 2026, 16(2), 191; https://doi.org/10.3390/diagnostics16020191 - 7 Jan 2026

Abstract

For decades, cervical insufficiency (CI) has been framed predominantly as a mechanical failure of the cervix resulting in painless mid-trimester dilatation. This disease-centered paradigm, reinforced by clinical teaching and administrative coding, does not fully capture the dynamic and biologically integrated nature of cervical [...] Read more.

For decades, cervical insufficiency (CI) has been framed predominantly as a mechanical failure of the cervix resulting in painless mid-trimester dilatation. This disease-centered paradigm, reinforced by clinical teaching and administrative coding, does not fully capture the dynamic and biologically integrated nature of cervical remodeling. Accumulating evidence suggests that cervical change is governed by coordinated mechanical, inflammatory, and immunologic interactions rather than by a purely anatomic defect. To outline a process-oriented conceptual framework that situates CI within the broader preterm-birth continuum, this perspective aims to integrate biomechanical, inflammatory, and immunologic dimensions of cervical remodeling and to emphasize that infection- and inflammation-related changes represent dynamic, potentially modifiable elements that may inform more individualized, biology-guided clinical decision-making. This Perspective traces the evolution from a traditional “disease entity” interpretation of CI toward a more integrated view of cervical remodeling as a dynamic, biology-responsive process. Emerging data suggest that when intra-amniotic infection or inflammation is appropriately managed, cervical competence may be partially restored, and mechanical support can be applied more safely in selected patients. Clinical observations indicate that infection-controlled cerclage is associated with meaningful prolongation of gestation. Earlier reports describing double-level mechanical reinforcement techniques conceptually align with contemporary interpretations of infection-controlled emergent cerclage by linking surgical timing with the underlying biology of cervical change. Rather than proposing a prescriptive management pathway, this framework highlights how mechanical, inflammatory, and immunologic factors may interact across heterogeneous CI etiologies and how individualized intervention may be guided by biologic context. Understanding CI as a dynamic rather than a fixed condition provides a framework that integrates its mechanical, inflammatory, and immunologic dimensions within the preterm birth continuum. Such a perspective encourages individualized, biology-informed interpretation of cervical change and supports more context-specific use of established interventions such as cerclage. By emphasizing developmental processes rather than a static defect, this approach seeks to bridge classical clinical practice with contemporary insights into cervical remodeling. Full article

(This article belongs to the Special Issue Advancements in Maternal–Fetal Medicine: 2nd Edition)

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16 pages, 1837 KB

Open AccessArticle

Impaired LC-NE System—A Novel Molecular Mechanism Underlying Health Disparity and Increased Prevalence of Alzheimer’s Disease Among African Americans

by Yu-Shin Ding, Elizabeth Pirraglia, Jiacheng Wang, Artem Mikheev, Jingyun Chen, Henry Rusinek and James Babb

Diagnostics 2026, 16(2), 190; https://doi.org/10.3390/diagnostics16020190 - 7 Jan 2026

Abstract

Background: The current biomarker classification system does not fully explain the increased prevalence of both Alzheimer’s disease (AD) and vascular risk factors for AD—such as diabetes and hypertension--among African Americans (AAs) compared to White participants. Research on cognitive aging has traditionally focused on [...] Read more.

Background: The current biomarker classification system does not fully explain the increased prevalence of both Alzheimer’s disease (AD) and vascular risk factors for AD—such as diabetes and hypertension--among African Americans (AAs) compared to White participants. Research on cognitive aging has traditionally focused on how declines in cortical and hippocampal regions influence cognition. However, tau pathology emerges decades before amyloid pathology, initially appearing in the brainstem, particularly in the locus coeruleus (LC), the primary source of the brain’s norepinephrine (NE). Further, postmortem studies suggest that the loss of LC neurons is a better predictor of AD symptom severity than amyloid-beta/neurofibrillary tangle pathology in any other brain region. Methods: Our decade-long studies in humans using a norepinephrine transporter (NET)-selective radiotracer ([¹¹C]MRB) have demonstrated that LC is uniquely vulnerable to aging and stress. In this retrospective study, regression slopes with age (RSAs) for regional NET availability were compared across groups and tested for statistical significance. Results: In our primary analysis, higher NET availability was observed in AAs (N = 14; 7 males aged 23–49), particularly at younger ages, as compared to White (N = 16; 11 males aged 24–55) participants. Our preliminary data also suggest that the rate of decline in NET availability is faster in AAs, with a potential trend toward a more pronounced effect in AA males as compared to White males (e.g., in the left thalamus, RSA was −3.03%/year [95%CI: −5.80% to 1.19%] for AA males vs. RSA = −0.14 for White males [95%CI: −0.79% to 0.47%]. Additionally, in the right anterior cingulate cortex, RSA was −3.4%/year [95%CI: −4.6% to −1.4%] for AA males, compared to RSA = 0.3%/year [95%CI: 0.04% to 1.03%] for White males). Conclusions: This report reveals that NET availability (measured with [¹¹C]MRB) can serve as a biomarker to index the function of the LC-NE system and that the fast-decline rate of NET in AAs implicates a potential molecular mechanism underlying health disparities observed in the disproportionate AD prevalence. Full article

(This article belongs to the Special Issue Diagnostic, Predictive and Prognostic Biomarkers for Neurodegenerative Diseases)

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Graphical abstract

12 pages, 3492 KB

Open AccessCase Report

Hepatic Vascular Involvement in Adenosine Deaminase 2 Deficiency (DADA2): Case Reports and Literature Review

by Mihaela Sparchez, Laura Damian, Mihai Adrian Socaciu, Otilia Fufezan and Zeno Sparchez

Diagnostics 2026, 16(2), 189; https://doi.org/10.3390/diagnostics16020189 - 7 Jan 2026

Abstract

Background and Clinical Significance: Deficiency of Adenosine Deaminase 2 (DADA2) is a rare monogenic vasculopathy characterised by systemic inflammatory and immunodeficiency features. Although neurological and haematological manifestations are well-documented, hepatic vascular involvement remains underappreciated. This report aims to describe the clinical and [...] Read more.

Background and Clinical Significance: Deficiency of Adenosine Deaminase 2 (DADA2) is a rare monogenic vasculopathy characterised by systemic inflammatory and immunodeficiency features. Although neurological and haematological manifestations are well-documented, hepatic vascular involvement remains underappreciated. This report aims to describe the clinical and imaging characteristics of hepatic vascular involvement in a patient with DADA2 and to illustrate the evolution of hepatic lesions during long-term Etanercept therapy. In addition, we provide a synthesis of the available evidence on hepatic manifestations in DADA2, emphasising vascular pathology, clinical presentation, and therapeutic implications. Case Presentation: We describe a girl with early-onset DADA2 presenting with recurrent systemic inflammation, hypogammaglobulinaemia, vasculopathy, and two childhood strokes, followed by the development of multiple FNH-like hepatic nodules on CEUS and MRI with persistently elevated GGT. Genetic testing confirmed biallelic ADA2 mutations, and treatment with Etanercept led to sustained clinical stabilisation and marked regression of liver lesions over a nine-year follow-up period. Her older sister, carrying the same mutations, showed a milder phenotype without hepatic involvement but experienced a mesenteric vascular event. Conclusions: Large regenerative nodules with an FNH-like appearance on CEUS or MRI have not been previously reported in this setting. In our patient, Etanercept therapy produced a favourable hepatic response, reflected by a significant reduction in both the number and size of the lesions. Our case contributes to the understanding of liver disease in DADA2 and the influence of imaging and treatment on the hepatic manifestations of the condition. Full article

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

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4 pages, 2634 KB

Open AccessInteresting Images

Fusion Imaging of ¹⁸F-FDG PET and MRI Identified an Inflammatory Esophageal Diverticulum in a Patient with Radioiodine-Refractory Differentiated Thyroid Cancer

by Jiamiao Yang, Peng Zhong, Jiahuan Yang, Xusen Yang and Libo Chen

Diagnostics 2026, 16(2), 188; https://doi.org/10.3390/diagnostics16020188 - 7 Jan 2026

Abstract

A radioiodine-refractory differentiated thyroid cancer patient with rising serum thyroglobulin (Tg) levels underwent ¹⁸F-FDG PET/CT scan, which showed a hypermetabolic region in the proximal segment of esophagus, leading to ambiguity in diagnosis. MRI was immediately added, and PET/MRI fusion image localized an [...] Read more.

A radioiodine-refractory differentiated thyroid cancer patient with rising serum thyroglobulin (Tg) levels underwent ¹⁸F-FDG PET/CT scan, which showed a hypermetabolic region in the proximal segment of esophagus, leading to ambiguity in diagnosis. MRI was immediately added, and PET/MRI fusion image localized an air-containing lesion interlinked with esophagus with enhanced T2 hyperintense mucosal signal, indicating an inflammatory esophageal diverticulum, which was subsequently verified by endoscopy. This case highlights the added value of PET/MRI image fusion in cases with inconclusive ¹⁸F-FDG PET/CT findings, requiring no additional tests and utilizing existing software, thereby minimizing the need for invasive procedures. Full article

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

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15 pages, 632 KB

Open AccessArticle

Predictive Accuracy of Ultrasound Biometry and Maternal Factors in Identifying Large-for-Gestational-Age Neonates at 30–34 Weeks

by Vasileios Bais, Antigoni Tranidou, Antonios Siargkas, Sofoklis Stavros, Anastasios Potiris, Dimos Sioutis, Chryssi Christodoulaki, Apostolos Athanasiadis, Apostolos Mamopoulos, Ioannis Tsakiridis and Themistoklis Dagklis

Diagnostics 2026, 16(2), 187; https://doi.org/10.3390/diagnostics16020187 - 7 Jan 2026

Abstract

Background/Objectives: To construct and compare multivariable prediction models for the early prediction of large-for-gestational-age (LGA) neonates, using ultrasound biometry and maternal characteristics. Methods: This retrospective cohort study analyzed data from singleton pregnancies that underwent routine ultrasound examinations at 30⁺⁰–34⁺⁰ [...] Read more.

Background/Objectives: To construct and compare multivariable prediction models for the early prediction of large-for-gestational-age (LGA) neonates, using ultrasound biometry and maternal characteristics. Methods: This retrospective cohort study analyzed data from singleton pregnancies that underwent routine ultrasound examinations at 30⁺⁰–34⁺⁰ weeks of gestation. Ultrasound parameters included fetal abdominal circumference (AC), head circumference (HC), femur length (FL), HC-to-AC ratio, mean uterine artery pulsatility index (mUtA-PI), and presence of polyhydramnios. LGA neonates were defined as those having a birthweight > 90th percentile. Logistic regression was used to evaluate associations between ultrasound markers and LGA after adjusting for the following maternal and pregnancy-related covariates: maternal age, body mass index, parity, gestational diabetes mellitus (GDM), pre-existing diabetes, previous cesarean section (PCS), assisted reproductive technology (ART) use, smoking, hypothyroidism, and chronic hypertension. Associations were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Three prognostic models were developed utilizing the following predictors: (i) biometric ultrasound measurements including AC, HC-to-AC ratio, FL, UtA-PI, and polyhydramnios (Model 1), (ii) a combination of biometric ultrasound measurements and clinical–maternal data (Model 2), and (iii) only the estimated fetal weight (EFW) (Model 3). Results: In total, 3808 singleton pregnancies were included in the analyses. The multivariable analysis revealed that AC (aOR 1.07, 95% CI [1.06, 1.08]), HC to AC (aOR 1.01, 95% CI [1.006, 1.01]), FL (aOR 1.01, 95% CI [1.009, 1.01]), and the presence of polyhydramnios (aOR 4.97, 95% CI [0.7, 58.8]) were associated with an increased risk of LGA, while a higher mUtA-PI was associated with a reduced risk (aOR 0.98, 95% CI [0.98, 0.99]). Maternal parameters, such as GDM, pre-existing diabetes, elevated pre-pregnancy BMI, absence of uterine artery notching, mUtA-PI, and multiparity, were significantly higher in the LGA group. Both models 1 and 2 showed similar performance (AUCs: 84.7% and 85.3%, respectively) and outperformed model 3 (AUC: 77.5%). Bootstrap and temporal validation indicated minimal overfitting and stable model performance, while decision curve analysis supported potential clinical utility. Conclusions: Models using biometric and Doppler ultrasound at 30–34 weeks demonstrated good discriminative ability for predicting LGA neonates, with an AUC up to 84.7%. Adding maternal characteristics did not significantly improve performance, while the biometric model performed better than EFW alone. Sensitivity at conventional thresholds was low but increased substantially when lower probability cut-offs were applied, illustrating the model’s threshold-dependent flexibility for early risk stratification in different clinical screening needs. Although decision curve analysis was performed to explore potential clinical utility, external validation and prospective assessment in clinical settings are still needed to confirm generalizability and to determine optimal decision thresholds for clinical application. Full article

(This article belongs to the Special Issue Advances in Ultrasound Diagnosis in Maternal Fetal Medicine Practice)

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20 pages, 3202 KB

Open AccessArticle

Voxel Normalization in LDCT Imaging: Its Significance in Texture Feature Selection for Pulmonary Nodule Malignancy Classification: Insights from Two Centers

by Chen-Hao Peng, Jhu-Fong Wu, Chu-Jen Kuo and Da-Chuan Cheng

Diagnostics 2026, 16(2), 186; https://doi.org/10.3390/diagnostics16020186 - 7 Jan 2026

Abstract

Background: Lung cancer is the leading cause of cancer-related mortality globally. Early detection via low-dose computed tomography (LDCT) can reduce mortality, but its implementation is challenged by the absence of objective diagnostic criteria and the necessity for extensive manual interpretation. Public datasets like [...] Read more.

Background: Lung cancer is the leading cause of cancer-related mortality globally. Early detection via low-dose computed tomography (LDCT) can reduce mortality, but its implementation is challenged by the absence of objective diagnostic criteria and the necessity for extensive manual interpretation. Public datasets like the Lung Image Database Consortium often lack pathology-confirmed diagnoses, which can lead to inaccuracies in ground truth labels. Variability in voxel sizes across these datasets also complicates feature extraction, undermining model reliability. Many existing methods for integrating nodule boundary annotations use deep learning models such as generative adversarial networks, which often lack interpretability. Methods: This study assesses the effect of voxel normalization on pulmonary nodule classification and introduces a Fast Fourier Transform-based contour fusion method as a more interpretable alternative. Utilizing pathology-confirmed LDCT data from 415 patients across two medical centers, both machine learning and deep learning models were developed using voxel-normalized images and attention mechanisms, including transformers. Results: The results demonstrated that voxel normalization significantly improved the overlap of features between datasets from two different centers by 64%, resulting in enhanced selection stability. In the ROI-based radiomics analysis, the top-performing machine-learning model achieved an accuracy of 92.6%, whereas the patch-based deep-learning models reached 98.5%. Notably, the FFT-based method provided a clinically interpretable integration of expert annotations, effectively addressing a major limitation of generative adversarial networks. Conclusions: Voxel normalization enhances reliability in pulmonary nodule classification while the FFT-based method offers a viable path toward interpretability in deep learning applications. Future research should explore its implications further in multi-center contexts. Full article

(This article belongs to the Special Issue A New Era in Diagnosis: From Biomarkers to Artificial Intelligence)

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13 pages, 1160 KB

Open AccessReview

Prenatal Use of Exome Sequencing and Chromosomal Microarray Analysis: Indications, Interpretation, and Gene Selection Strategies

by Laia Rodriguez-Revenga, Victoria Ardiles-Ruesjas and Antoni Borrell

Diagnostics 2026, 16(2), 185; https://doi.org/10.3390/diagnostics16020185 - 7 Jan 2026

Abstract

As genomic technologies continue to evolve, understanding the scope and limitations of available prenatal testing methods is essential for accurate diagnosis and counseling. Chromosomal microarray analysis (CMA) and exome sequencing (ES) have emerged as key complementary tools in this setting. This review aims [...] Read more.

As genomic technologies continue to evolve, understanding the scope and limitations of available prenatal testing methods is essential for accurate diagnosis and counseling. Chromosomal microarray analysis (CMA) and exome sequencing (ES) have emerged as key complementary tools in this setting. This review aims to outline the technical principles underlying CMA and ES and to compare their diagnostic capabilities and limitations in the prenatal context. This narrative review includes a literature search, with additional relevant articles identified through manual screening of reference lists from key publications and review articles. Due to the narrative nature of this review, no formal inclusion or exclusion criteria or quantitative synthesis were applied. Special focus was placed on clinical indications, variant interpretation challenges—particularly uncertain and incidental findings—gene selection strategies, and implications for prenatal counseling. Indications for both tests have increased over time but differ substantially. CMA is becoming the standard prenatal genetic test, particularly in the evaluation of fetal structural anomalies, whereas ES remains restricted to selected fetal structural anomalies. Interpretation of molecular results remains a major challenge, especially for variants of uncertain significance and incidental findings with unclear or unexpected implications for pregnancy management. For ES, agnostic gene selection strategies showed superior diagnostic yield compared with phenotype-driven approaches, likely reflecting the limited characterization of prenatal phenotypes. Continuous refinement of clinical indications, bioinformatic pipelines, variant classification criteria, and gene curation strategies is critical to ensure that prenatal results are accurate and clinically meaningful. Together, ongoing improvements in technology, interpretation, and clinical integration have the potential to transform prenatal genomics into a more precise, informed, and ethically responsible field. Full article

(This article belongs to the Special Issue Game-Changing Concepts in Reproductive Health)

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21 pages, 2156 KB

Open AccessReview

Unmasking the Apex: Multimodality Imaging for the Evaluation of Left Ventricular Apical Obliteration

by Ilaria Dentamaro, Marco Maria Dicorato, Paolo Basile, Maria Cristina Carella, Francesco Mangini, Rita Musci, Roberta Ruggieri, Eduardo Urgesi, Laura Piscitelli, Sergio Dentamaro, Gianluca Pontone, Cinzia Forleo, Marco Matteo Ciccone and Andrea Igoren Guaricci

Diagnostics 2026, 16(2), 184; https://doi.org/10.3390/diagnostics16020184 - 7 Jan 2026

Abstract

Left ventricular (LV) apical obliteration represents a convergent imaging phenotype arising from diverse cardiac conditions, including thrombotic, hypertrophic, infiltrative, congenital, and neoplastic diseases. These conditions, despite sharing overlapping morphological features, require profoundly different management strategies. In this context, an accurate characterization of the [...] Read more.

Left ventricular (LV) apical obliteration represents a convergent imaging phenotype arising from diverse cardiac conditions, including thrombotic, hypertrophic, infiltrative, congenital, and neoplastic diseases. These conditions, despite sharing overlapping morphological features, require profoundly different management strategies. In this context, an accurate characterization of the LV apex is a cornerstone point, and can be performed through various techniques. Advances in multimodality imaging have substantially improved diagnostic precision, allowing clinicians to differentiate true obliteration from mimicking conditions such as hypertrabeculation, apical hypertrophy, or subendocardial fibrosis. This review provides a comprehensive overview of the anatomical variability of the LV apex and its implications for imaging interpretation. We appraise the role of echocardiography, including contrast-enhanced and speckle-tracking studies—alongside cardiac magnetic resonance (CMR), computed tomography (CT), and selective nuclear imaging in the evaluation of apical pathology. For each principal cause of apical obliteration—LV thrombus, apical hypertrophic cardiomyopathy, left ventricular non-compaction, endomyocardial fibrosis, cardiac amyloidosis, and intracardiac tumors—we outline key diagnostic clues, imaging red flags, and distinguishing tissue characteristics. Special emphasis is given to the incremental value of CMR for tissue characterization, thrombus detection, and fibrosis mapping, as well as to the interpretative challenges posed by apical foreshortening, near-field artefacts, and suboptimal acoustic windows. A practical, stepwise imaging framework is proposed to guide clinicians through the differential diagnosis of apical obliteration using an integrated multimodality approach. Future directions include the incorporation of 4D flow, advanced mapping techniques, and artificial intelligence-powered analysis to refine apical phenotyping and identify early disease signatures. Recognizing the full spectrum of apical pathology and its imaging manifestations is essential to prevent misdiagnosis, enable timely therapeutic decisions, and improve risk stratification. Full article

(This article belongs to the Special Issue Advances in Non-Invasive Diagnostic Technologies for Heart Diseases)

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11 pages, 1516 KB

Open AccessCase Report

First Case of Cutaneous Coinfection with Aspergillus flavus and Klebsiella pneumoniae: Case Report and Literature Review

by Simona Maria Borta, Zsolt Gyori, Cosmin Catalin Bacean, Romana Olivia Popetiu, Cristina Petrine, Melani Zarici, Lavinia Palaghian and Adrian Silviu Crisan

Diagnostics 2026, 16(2), 183; https://doi.org/10.3390/diagnostics16020183 - 7 Jan 2026

Abstract

Background and Clinical Significance: Cutaneous aspergillosis caused by Aspergillus flavus is rare and coinfection with Klebsiella pneumoniae was reported only in pulmonary disease. Case Presentation: We describe a 57-year-old woman with no prior comorbidities who developed septic shock requiring intensive care, broad-spectrum antibiotics, [...] Read more.

Background and Clinical Significance: Cutaneous aspergillosis caused by Aspergillus flavus is rare and coinfection with Klebsiella pneumoniae was reported only in pulmonary disease. Case Presentation: We describe a 57-year-old woman with no prior comorbidities who developed septic shock requiring intensive care, broad-spectrum antibiotics, corticosteroids, and renal replacement therapy. Six days after discharge, she was readmitted with fever, leukopenia, thrombocytopenia, cavitary lung lesions, and multiple erythematous nodules on the limbs and mammary regions. Bronchial aspirate cultures detected K. pneumoniae, while progressive cutaneous lesions required surgical debridement. Histopathology revealed angioinvasive septate hyphae, and MALDI-TOF identified A. flavus. The K. pneumoniae strain was extensively drug resistant; A. flavus was susceptible only to azoles. Despite targeted therapy, lesions progressed requiring bilateral mastectomy. Conclusions: This case illustrates a previously unreported scenario in which secondary immunosuppression after severe sepsis led to concurrent cutaneous A. flavus infection and extensively drug-resistant (XDR) K. pneumoniae. Early recognition of mixed fungal–bacterial infections is essential for appropriate management. Full article

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

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22 pages, 30494 KB

Open AccessArticle

On Construction of Tibial Plateau Fracture Detection in Different Radiographic Views Using YOLO Models

by Shun-Ping Wang, Han-Ting Shih, Yu-Xiang Liao, Chih-Han Wei, Jung-Chun Liu, Endah Kristiani and Chao-Tung Yang

Diagnostics 2026, 16(2), 182; https://doi.org/10.3390/diagnostics16020182 - 6 Jan 2026

Abstract

Background/Objectives: Tibial plateau fractures are difficult to detect using X-ray imaging due to limited three-dimensional visibility. This study evaluated the performance of four You Only Look Once (YOLO) deep learning models trained on different radiographic views for fracture detection. Methods: A total of [...] Read more.

Background/Objectives: Tibial plateau fractures are difficult to detect using X-ray imaging due to limited three-dimensional visibility. This study evaluated the performance of four You Only Look Once (YOLO) deep learning models trained on different radiographic views for fracture detection. Methods: A total of 1489 knee X-rays were collected from a tertiary referral hospital, comprising 727 fracture images and 762 non-fracture images. YOLOv4, YOLOv5, YOLOv8, and YOLOv9 were each trained using anteroposterior (AP), lateral, and combined views. Results: YOLO models trained on AP views consistently outperformed those trained on other views. YOLOv9 trained on AP images achieved the highest accuracy, specificity, precision, F1-score, and area under the curve (AUC) of 0.99, with both sensitivity and negative predictive value (NPV) at 1.00. YOLOv8 trained on AP views reached 0.97 across all metrics with an AUC of 0.98. YOLOv5 trained on AP images achieved an accuracy and F1-score of 0.98, a sensitivity and NPV of 0.97, and an AUC of 1.00. YOLOv4 trained on AP views showed slightly lower performance, with an accuracy and F1-score of 0.96 and an AUC of 1.00. External validation confirmed the strong generalizability of AP-trained models, particularly YOLOv9, which reached an accuracy of 0.87, a sensitivity of 1.00, a specificity of 0.75, a precision of 0.80, an NPV of 1.00, an F1-score of 0.88, and an AUC of 0.93. Artificial intelligence-assisted YOLO models showed strong potential in detecting tibial plateau fractures. Conclusions: Models trained on AP views consistently achieved better diagnostic accuracy than those using other views. Among all, YOLOv9 delivered the best results, highlighting the benefits of newer deep learning architectures. Full article

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

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8 pages, 282 KB

Open AccessOpinion

Unifying Serum Creatinine and Urine Output in a Single On-Time AKI Severity Criterion: Is It All About the Rate of Creatinine Being Excreted by the Kidneys?

by Alexandre Toledo Maciel

Diagnostics 2026, 16(2), 181; https://doi.org/10.3390/diagnostics16020181 - 6 Jan 2026

Abstract

Serum creatinine (sCr) and urine output (UO) have long been considered the cornerstones of acute kidney injury (AKI) severity criteria. Many articles were previously published discussing the prognostic relevance of fulfilling either one or both AKI criteria. However, sCr and UO must not [...] Read more.

Serum creatinine (sCr) and urine output (UO) have long been considered the cornerstones of acute kidney injury (AKI) severity criteria. Many articles were previously published discussing the prognostic relevance of fulfilling either one or both AKI criteria. However, sCr and UO must not be considered independent variables because they are physiologically linked despite having distinct chronologies as AKI markers. An increase in sCr is a late manifestation of decreased renal function and body creatinine accumulation and not an on-time surrogate for a decreasing glomerular filtration rate. On the other hand, oliguria is not a single entity, and its interpretation relies on urine’s biochemical composition as well as its threshold pathological output value, which is somewhat controversial. In the present article, the current practice of evaluating sCr and UO separately is questioned and the idea that they can eventually be considered different expressions of the same variable of interest (the urine creatinine excretion) is highlighted. Full article

(This article belongs to the Special Issue Diagnostics in the Emergency and Critical Care Medicine)

28 pages, 2173 KB

Open AccessArticle

The Relationship Between Bone Health Status of Post-Menopausal Women with Non-Functional Adrenal Tumours/Mild Autonomous Cortisol Secretion and Their Baseline Morning Adrenocorticotropic Level

by Alexandra-Ioana Trandafir, Oana-Claudia Sima, Nina Ionovici, Dana Manda, Mihai Costachescu and Mara Carsote

Diagnostics 2026, 16(2), 180; https://doi.org/10.3390/diagnostics16020180 - 6 Jan 2026

Abstract

Background. Glucocorticoid-induced osteoporosis represents a well-known type of secondary osteoporosis (SOp). While the most prevalent sub-category includes corticotherapy, another important contributor is represented by Cushing’s syndrome. In this traditional landscape, adrenal incidentalomas do not involve a standard cause of SOp, since most [...] Read more.

Background. Glucocorticoid-induced osteoporosis represents a well-known type of secondary osteoporosis (SOp). While the most prevalent sub-category includes corticotherapy, another important contributor is represented by Cushing’s syndrome. In this traditional landscape, adrenal incidentalomas do not involve a standard cause of SOp, since most of them are non-functioning adrenal tumours (NFATs). Yet, 30–40% of them are not entirely “non-functioning”, due to mild autonomous cortisol secretion (MACS). Despite not being a guideline-based diagnosis, a lower ACTH might point to various NFATs/MACS complications. Objective. This study aimed to determine the relationship between the bone health status of post-menopausal women with NFATs/MACS and their baseline morning ACTH level. The bone health indicators were DXA, FRAX, and bone remodelling markers. Methods. This was a retrospective, real-life, transversal study in adult females who were hospitalized in a single tertiary centre of endocrinology. They were all anti-osteoporotic drug-naïve. The subjects underwent CT and DXA scanning and a 1 mg dexamethasone suppression test (DST). Results. The cohort (sample size of N = 84 patients, 61.49 ± 7.86 years) had a type 2 diabetes rate of 18%, arterial hypertension rate of 75%, and a dyslipidemia rate of 78%. Median ACTH was 11.89 pg/mL. The prevalence of MACS was 30.95%. The mean largest tumour diameter (LTD) was 2.25 ± 0.99 cm. ACTH correlated with second-day cortisol after the 1 mg DST (r = −0.301, p = 0.024), and LTD (r = −0.434, p < 0.001). ROC analysis for the bone resorption marker CrossLaps showed an AUC of 0.647 (p = 0.05), with the highest Youden index for the cut-off at 0.32 ng/mL (sensitivity 87.50%, specificity 39.50%). Bone impairment (osteoporosis + osteopenia) was found in 65% of patients, with an osteoporotic fracture prevalence of 4.76%. The lowest mean T-score (−1.12 ± 1.00) showed osteopenia, and the median trabecular bone score pointed a partially degraded microarchitecture [median (interquartile interval): 1.320 (1.230, 1.392)]. FRAX and FRAXplus estimations correlated with bone mineral density (BMD) at all three central DXA sites, regardless of the ACTH cut-off. Patients with a low ACTH (<10 pg/mL) displayed similar bone/adrenal features when compared to those with normal ACTH, except forbut they had a higher MACS rate (45.45% versus 21.57%, p = 0.021) and a larger LTD (2.67 ± 0.98 versus 1.98 ± 0.92 cm, p = 0.003). Fracture estimation showed that only in patients with a low ACTH, the 10-year fracture risk for major osteoporotic fractures (MOF) adjusted for lumbar BMD was lower than the risk for MOF adjusted for diabetes (p = 0.036), and the 10-year hip fracture risk was lower when adjusted for lumbar BMD (p = 0.007). ACTH correlated with lumbar BMD (r = 0.591, p = 0.002) only in the group with an ACTH < 10 pg/mL, suggesting its potential usefulness as a bone biomarker in these cases. On the other hand, MACS-negative subjects with a low ACTH versus those with a normal ACTH showed higher CrossLaps (0.60 ± 0.27 versus 0.42 ± 0.21 ng/mL, p = 0.022), indicating an elevated bone resorption even in patients with tumours that are regarded as true non-secretors. Conclusions. A subgroup of patients diagnosed with NFATs/MACS might be prone to skeletal damage, and biomarkers such as ACTH (specifically, suppressed ACTH) might serve as a surrogate pointer to help refine this higher risk in daily practice. Further research to address other ACTH cut-offs will place ACTH assays in the overall bone status evaluation in these patients, most probably not as a single biomarker, but in addition to other assays. Full article

(This article belongs to the Special Issue Current Diagnosis and Management of Metabolic Bone Disease)

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21 pages, 4339 KB

Open AccessArticle

Efficient Ensemble Learning with Curriculum-Based Masked Autoencoders for Retinal OCT Classification

by Taeyoung Yoon and Daesung Kang

Diagnostics 2026, 16(2), 179; https://doi.org/10.3390/diagnostics16020179 - 6 Jan 2026

Abstract

Background/Objectives: Retinal optical coherence tomography (OCT) is essential for diagnosing ocular diseases, yet developing high-performing multiclass classifiers remains challenging due to limited labeled data and the computational cost of self-supervised pretraining. This study aims to address these limitations by introducing a curriculum-based [...] Read more.

Background/Objectives: Retinal optical coherence tomography (OCT) is essential for diagnosing ocular diseases, yet developing high-performing multiclass classifiers remains challenging due to limited labeled data and the computational cost of self-supervised pretraining. This study aims to address these limitations by introducing a curriculum-based self-supervised framework to improve representation learning and reduce computational burden for OCT classification. Methods: Two ensemble strategies were developed using progressive masked autoencoder (MAE) pretraining. We refer to this curriculum-based MAE framework as CurriMAE (curriculum-based masked autoencoder). CurriMAE-Soup merges multiple curriculum-aware pretrained checkpoints using weight averaging, producing a single model for fine-tuning and inference. CurriMAE-Greedy selects top-performing fine-tuned models from different pretraining stages and ensembles their predictions. Both approaches rely on one curriculum-guided MAE pretraining run, avoiding repeated training with fixed masking ratios. Experiments were conducted on two publicly available retinal OCT datasets, the Kermany dataset for self-supervised pretraining and the OCTDL dataset for downstream evaluation. The OCTDL dataset comprises seven clinically relevant retinal classes, including normal retina, age-related macular degeneration (AMD), diabetic macular edema (DME), epiretinal membrane (ERM), retinal vein occlusion (RVO), retinal artery occlusion (RAO), and vitreomacular interface disease (VID) and the proposed methods were compared against standard MAE variants and supervised baselines including ResNet-34 and ViT-S. Results: Both CurriMAE methods outperformed standard MAE models and supervised baselines. CurriMAE-Greedy achieved the highest performance with an area under the receiver operating characteristic curve (AUC) of 0.995 and accuracy of 93.32%, while CurriMAE-Soup provided competitive accuracy with substantially lower inference complexity. Compared with MAE models trained at fixed masking ratios, the proposed methods improved accuracy while requiring fewer pretraining runs and reduced model storage for inference. Conclusions: The proposed curriculum-based self-supervised ensemble framework offers an effective and resource-efficient solution for multiclass retinal OCT classification. By integrating progressive masking with snapshot-based model fusion, CurriMAE methods provide high performance with reduced computational cost, supporting their potential for real-world ophthalmic imaging applications where labeled data and computational resources are limited. Full article

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

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13 pages, 251 KB

Open AccessReview

Ultrasound Assessment Before Complex or Difficult Cesarean Section

by Kwok-yin Leung

Diagnostics 2026, 16(2), 178; https://doi.org/10.3390/diagnostics16020178 - 6 Jan 2026

Abstract

Complex or difficult cesareans are associated with significant short- and long-term complications. The complication rate increases with the increasing number of cesareans, and the incidence of cesarean section is increasing. To accurately identify women at high risk of surgical difficulty during a cesarean, [...] Read more.

Complex or difficult cesareans are associated with significant short- and long-term complications. The complication rate increases with the increasing number of cesareans, and the incidence of cesarean section is increasing. To accurately identify women at high risk of surgical difficulty during a cesarean, ultrasound, in addition to clinical assessment, can be used to evaluate many risk factors, including placenta previa, placenta accreta spectrum (PAS) disorders, fibroids, severe pelvic adhesions, and membranous fetal vessels. The role of preoperative ultrasound is to identify ultrasonographic signs of anatomic changes that may affect the risk of intraoperative complications in subsequent cesarean sections. It is important to look for maternal problems as well as fetal problems. Ultrasound is a well-established practice in obstetrical care as it is easily available, accessible, easy to perform, and well accepted by women. However, there are few studies on the role of preoperative ultrasound in the management of complex or difficult cesareans beyond the risk assessment of PAS. Currently, preoperative ultrasound is mostly performed in selected cases only, with the exception in some settings. The aim of this review article is to discuss the benefits and the use of ultrasound assessment before different types of complex or difficult cesareans. Whether ultrasound assessment should be performed before all cesarean sections will also be discussed. Full article

(This article belongs to the Special Issue Advances in Ultrasound Diagnosis in Maternal Fetal Medicine Practice)

21 pages, 1339 KB

Open AccessArticle

Understanding the Drivers of Hypothyroidism in Patients Undergoing Chronic Hemodialysis

by Ioana Adela Ratiu, Elena Emilia Babeș, Laura Monica Georgescu, Ozana Hocopan, Danut Dejeu, Corina Moisa, Daria Nicoleta Gavra and Cristian Adrian Ratiu

Diagnostics 2026, 16(2), 177; https://doi.org/10.3390/diagnostics16020177 - 6 Jan 2026

Abstract

Background/Objectives: Hypothyroidism is highly prevalent among HD patients, due to cumulative disturbances in thyroid hormone synthesis, metabolism, and clearance. Subclinical hypothyroidism—defined by elevated TSH with normal fT₄—is common in HD, along with a distinct entity, the low-T₃ syndrome. This [...] Read more.

Background/Objectives: Hypothyroidism is highly prevalent among HD patients, due to cumulative disturbances in thyroid hormone synthesis, metabolism, and clearance. Subclinical hypothyroidism—defined by elevated TSH with normal fT₄—is common in HD, along with a distinct entity, the low-T₃ syndrome. This study aims to examine the predictors of hypothyroidism in HD and its impact on cardiovascular morbidity and mortality. Methods: We conducted a retrospective cohort study including 282 hemodialysis (HD) patients, with evaluated thyroid function and monitored from January 2022 to June 2025. A total of 66 (23.4%) patients with hypothyroidism were identified, 15 (5.31%) of whom had autoimmune thyroiditis. Subclinical hypothyroidism was documented in 31.81% of the hypothyroid patients. Results: Hypothyroidism occurred predominantly in females (63.63% vs. 41.2%, p ≤ 0.001) and was associated with higher BMI (27.856 ± 6.216 vs. 25.759 ± 6.080, p = 0.017), hypoalbuminemia (3.534 ± 0.547 vs. 3.725 ± 0.471, p = 0.006), elevated LDL-cholesterol and triglyceride levels, as well as with amiodarone use. Hypothyroidism was further associated with atrial fibrillation (33.33 vs. 19.9%, p = 0.022), coronary artery revascularization procedures (18.18% vs. 9.72%, p = 0.047), neoplastic disease (25.75% vs. 12.03%, p = 0.008), and cancer-related mortality (10.6% vs. 1.85%, p = 0.001). Multivariable regression analysis revealed the following predictors of hypothyroidism: female sex (OR 3.848, 95%CI 1.704–8.693, p = 0.001), BMI (OR 1.072, 95%CI 1.007–1.146, p = 0.031), hypoalbuminemia (OR 0.412, 95%CI 0.177–0.962, p = 0.040), hypertriglyceridemia (OR 1.088, 95% CI 1.001–1.016, p = 0.022) and amiodarone use (OR 6.698, 95%CI 1.744–25.722, p = 0.006). Patients with autoimmune thyroiditis did not exhibit clinical or biochemical differences compared with other hypothyroid patients. Subclinical hypothyroidism was associated with longer HD duration (10.476 ± 7.910 vs. 6.567 ± 5.541, p = 0.003), dyslipidemia, hypertension, atrial fibrillation and amiodarone use. Cardiovascular conditions—particularly atrial fibrillation and ischemic coronary disease requiring revascularization—are more common in HD patients with clinical or subclinical hypothyroidism. However, in our cohort, the Kaplan–Meier survival curves at 12, 24, and 36 months for patients with both subclinical and clinical hypothyroidism do not show significant differences in cardiac or overall mortality. Conclusions: The increased incidence of hypothyroidism in HD patients, together with its impact on cardiovascular pathology, underscores the need for multidisciplinary management and supports annual routine assessment of thyroid hormones—particularly in overweight or dyslipidemic patients and in those receiving amiodarone. Full article

(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment of Kidney Diseases: 2nd Edition)

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14 pages, 2415 KB

Open AccessArticle

Improved Quantification of ICG Perfusion Through Motion Compensation in Fluorescence-Guided Surgery

by Sermed Ellebæk Nicolae, Thomas Baastrup Piper, Nikolaj Albeck Nerup, Michael Patrick Achiam and Morten Bo Søndergaard Svendsen

Diagnostics 2026, 16(2), 176; https://doi.org/10.3390/diagnostics16020176 - 6 Jan 2026

Abstract

Background/Objectives: Motion artifacts significantly distort fluorescence measurements during surgical perfusion assessment, potentially leading to incorrect clinical decisions. This study evaluates the efficacy of automated motion compensation (MC) in quantitative indocyanine green (q-ICG) imaging to improve the accuracy of perfusion assessment. Methods: [...] Read more.

Background/Objectives: Motion artifacts significantly distort fluorescence measurements during surgical perfusion assessment, potentially leading to incorrect clinical decisions. This study evaluates the efficacy of automated motion compensation (MC) in quantitative indocyanine green (q-ICG) imaging to improve the accuracy of perfusion assessment. Methods: Frames from ICG perfusion assessment during 17 pancreaticoduodenectomies were analyzed. Regions of interest (ROIs) were systematically placed on each frame series, and automated MC was applied to track tissue movement. Performance was evaluated by comparing MC with surgeon-adjusted placement using multiple image quality metrics and analyzing perfusion metrics on time–intensity curves. Principal Component Analysis (PCA) was applied to explore whether image patterns could distinguish between successful and unsuccessful motion compensation. Results: Automated motion compensation successfully corrected motion artifacts in 67.5% of frame sequences, achieving comparable performance to surgeon-guided adjustments. PCA demonstrated clear separation between sufficient and insufficient corrections (AUC = 0.80). At the population level, MC did not significantly change perfusion slope (t(59) = 1.60, p = 0.11) or time-to-peak (Tmax; t(58) = 0.81, p = 0.42). Bland–Altman analysis showed a mean bias of −0.54 (SD = 3.32) for slope and 24.95 (SD = 238.40) for Tmax. At the individual level, 86.7% of slope and 79.7% of Tmax values differed by ≥10% after MC, with mean absolute percentage changes of 108.5% (median 37.8%) and 431.5% (median 65.9%), respectively. Conclusions: MC effectively reduces motion artifacts in fluorescence-guided perfusion assessment. By improving the precision of ICG-derived parameters, this technology enhances measurement reliability and represents an enabler for accurate intraoperative perfusion quantification. Full article

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

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19 pages, 1054 KB

Open AccessArticle

Evaluation of Functional T-Cell Assays That Predict Causal Allergens in Eosinophilic Esophagitis

by Julianna Dilollo, Cleandre M. Guerrier, Ignacio De La Torre Saenz Rico, Elizabeth Martin, Susan Lee, Michael Pratt, Pavithra Vinnakota, Walter Faig, Michele E. Paessler, Jonathan M. Spergel and David A. Hill

Diagnostics 2026, 16(2), 175; https://doi.org/10.3390/diagnostics16020175 - 6 Jan 2026

Abstract

Background: Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven disease of the esophagus that causes considerable morbidity. Elimination of allergenic foods from a patient’s diet is a highly effective treatment. However, existing allergen testing modalities are not effective at identifying EoE-causal foods. [...] Read more.

Background: Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven disease of the esophagus that causes considerable morbidity. Elimination of allergenic foods from a patient’s diet is a highly effective treatment. However, existing allergen testing modalities are not effective at identifying EoE-causal foods. We sought to determine the extent to which positive results for two functional T-cell assays, the EoE Milk Test and EoE Soy Test, associated with the clinical outcomes of EoE milk allergy and EoE soy allergy, respectively. Methods: Subjects were enrolled into one of two study designs: a prospective observational study or a retrospective case/control study. Additional control samples were obtained from an institutional core. The EoE Milk and Soy Tests were performed on peripheral blood samples, and the association between positive tests and clinical outcomes was determined using Receiver Operating Characteristic curves and other performance measures. Results: The EoE Milk Test maintained reliability regardless of disease activity or recent milk consumption and had 87% sensitivity and 83% specificity for EoE milk allergy in all study subjects (control and EoE). The EoE Soy Test had 90% sensitivity and 93% specificity in all subjects. Conclusions: Our evaluation of the EoE Milk and Soy Tests demonstrates that these functional T-cell assays hold promise as a predictive tool for identifying causal allergens in eosinophilic esophagitis patients. Full article

(This article belongs to the Special Issue Eosinophilic Gastrointestinal Disorders: Advances in Diagnosis and Management)

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10 pages, 472 KB

Open AccessArticle

Clinical Validation of DNA Methylation Detection in Cervical Exfoliated Cells for Endometrial Cancer in Women with Suspected Lesions

by Yi Yu, Tingting Su, Hongwei Zhang, Qing Li, Qing Cong, Long Sui and Limei Chen

Diagnostics 2026, 16(2), 174; https://doi.org/10.3390/diagnostics16020174 - 6 Jan 2026

Abstract

Background/Objectives: Currently, no non-invasive detection method for endometrial cancer (EC) is recommended in clinical practice worldwide. This study aimed to evaluate the clinical value of detecting DNA methylation of CDO1 and CELF4 (CDO1m/CELF4m) in exfoliated cervical cells for the detection of EC [...] Read more.

Background/Objectives: Currently, no non-invasive detection method for endometrial cancer (EC) is recommended in clinical practice worldwide. This study aimed to evaluate the clinical value of detecting DNA methylation of CDO1 and CELF4 (CDO1m/CELF4m) in exfoliated cervical cells for the detection of EC in women with suspected endometrial lesions. Methods: A total of 2164 patients scheduled for hysteroscopic surgery due to suspected endometrial lesions at the Obstetrics and Gynecology Hospital of Fudan University between July 2023 and May 2024 were prospectively enrolled. Preoperative exfoliated cervical cells were collected for dual-gene methylation testing. Clinical data and endometrial thickness measured by transvaginal sonography (TVS) were recorded. Hysteroscopic histopathological diagnosis served as the gold standard to evaluate the performance of methylation testing alone and in combination with TVS. Results: This study included 2164 patients, comprising 33 EC cases, 31 cases of endometrial intraepithelial neoplasia (EIN), and 2100 cases of non-endometrial lesions, with mean ages of 51.7 ± 6.4, 49.5 ± 8.9, and 44.7 ± 9.8 years, respectively (p < 0.001). For EC detection, CDO1m/CELF4m positivity showed a sensitivity of 93.94% (95% CI: 79.77–99.26%), specificity of 96.7% (95% CI: 95.92–97.47%), positive predictive value (PPV) of 31.0% (95% CI: 25.96–36.53%), and negative predictive value (NPV) of 99.90% (95% CI: 99.63–99.98%). For EIN detection, the sensitivity was 83.87%, specificity 97.95%, PPV 37.68%, and NPV 99.76%. Combining TVS with DNA methylation detection further improved the sensitivity and NPV for both EC and EIN detection. Conclusions: DNA methylation detection in exfoliated cervical cells demonstrates high sensitivity and specificity for EC detection. The combination with TVS further enhances sensitivity and NPV, offering a simple and non-invasive triage strategy for patients with suspected endometrial lesions. This study was registered in China Clinical Trial Registry (ChiCTR2200055991) on 30 January 2023. Full article

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

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Diagnostics, Volume 16, Issue 2 (January-2 2026) – 20 articles

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