Diagnostics

16 pages, 5298 KB

Open AccessArticle

CT-Based Reference Values for Splenic Artery and Vein Diameters in Individuals Aged 1–80 Years

by Iklil Eryılmaz, Fırat Aslan, Serhat Binici, Uğur Yanç, Bülent Sönmez, Veysel Tahiroğlu, Burhan Beger, Muzaffer Onder Oner, Berke Bulut Yüktaşır, Barış Ten, Murat Gölpınar, Turan Koç and Orhan Beger

Diagnostics 2026, 16(14), 2267; https://doi.org/10.3390/diagnostics16142267 - 20 Jul 2026

Abstract

Objectives: Demographic features of subjects, such as body mass index, height, weight, age, or sex, may affect diameters of vessels such as the splenic artery (SA) and splenic vein (SV). Some studies use alternative anatomical indicators, including the body of the first lumbar [...] Read more.

Objectives: Demographic features of subjects, such as body mass index, height, weight, age, or sex, may affect diameters of vessels such as the splenic artery (SA) and splenic vein (SV). Some studies use alternative anatomical indicators, including the body of the first lumbar vertebra (L1), to improve standardization in the assessment of vascular pathologies. This study aimed to evaluate the relationship between splenic vessel diameters (SA and SV) and L1 using abdominopelvic computed tomography images obtained from individuals aged 1–80 years. Methods: Radiologic images of 800 subjects were included in the examination. Proximal (SA1 and SV1), middle (SA2 and SV2) and distal (SA3 and SV3) calibers of SA and SV were measured. Ratios of vessel calibers to the transverse diameter of the body of L1 (L1TD) were calculated. Results: Age had a clear influence on the diameters of SA and SV. SV1 showed a steady increase until the early fifties, followed by a decline beginning in the seventies. Both SV2 and SV3 enlarged until the early twenties, after which no significant variation was observed. SA1, SA2, and SA3 gradually increased from 1 year of age through the early fifties, but demonstrated a statistically significant reduction at older ages. The ratios of SA and SV diameters to L1TD were highest during the first decade of life and dropped markedly in the second decade. Following this period, these ratios generally tended to rise initially and then decline with further aging. Conclusions: This study provides age-specific CT-based reference values for SA and SV diameters and their ratios to the L1 vertebral body. Since L1 is readily identifiable on routine computed tomography, these ratios may provide a practical complementary anatomical reference. Further studies are warranted to validate their clinical applicability. Full article

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

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24 pages, 948 KB

Open AccessReview

Why Radiomics Rarely Reaches the Clinic: Reproducibility, Validation, and Evidence Gap—A Critical Narrative Review

by Jacopo Pozzi, Jacopo D’Argenzio, Serena Carriero, Maurizio Cè, Dario D’Arrigo, Pierpaolo Biondetti, Carolina Lanza, Salvatore Alessio Angileri, Matilde Pavan, Rossella Catona and Gianpaolo Carrafiello

Diagnostics 2026, 16(14), 2266; https://doi.org/10.3390/diagnostics16142266 - 20 Jul 2026

Abstract

Radiomics has produced tens of thousands of publications yet almost no handcrafted radiomic signatures in routine clinical use, and the reasons are increasingly understood to be problems of reproducibility and clinical translation rather than of algorithms. This critical narrative review argues that the [...] Read more.

Radiomics has produced tens of thousands of publications yet almost no handcrafted radiomic signatures in routine clinical use, and the reasons are increasingly understood to be problems of reproducibility and clinical translation rather than of algorithms. This critical narrative review argues that the field systematically generates paper-grade evidence—findings sufficient to publish—far faster than decision-grade evidence—findings sufficient to change clinical practice. Drawing on meta-scientific research, we describe seven fragility mechanisms (publication bias, analytical flexibility, underpowering, HARKing [hypothesizing after the results are known], citation distortion, cognitive bias, and misaligned incentives) and show why radiomics is structurally exposed to all of them simultaneously: high-dimensional feature spaces, acquisition-dependent measurement instability, segmentation variability, retrospective single-centre data, small samples, and leakage-prone validation. We then summarise empirical evidence on the radiomics literature, which remains pervaded by suboptimal methodological quality, near-absent negative results, limited external validation, sparse calibration and clinical-utility assessment, low data and code sharing, and a measurable retraction signal. We interpret these patterns as the output of a self-reinforcing system rather than isolated errors, and argue that better algorithms alone cannot resolve them. Finally, we argue that closing this gap requires not better models but evidentiary discipline: the consistent, enforceable application of standards the field already has, and the calibration of published claims to the strength of the underlying evidence. Full article

(This article belongs to the Special Issue Recent Advances in Diagnostic and Interventional Radiology)

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14 pages, 1100 KB

Open AccessArticle

Head Trauma Mechanisms and Neuroimaging Findings in Psychiatric Inpatients Referred for Neurosurgical Consultation

by Ilhan Aydin, Efecan Cekic, Berkay Kef, Asya Gokceli, Egemen Gok, Orhun Mete Cevik, Ahmet Oz, Melih Ucer, Ozden Erhan Sofuoglu, Ceyhan Oflezer, Erhan Emel, Murad Asilturk and Sahin Hanalioglu

Diagnostics 2026, 16(14), 2265; https://doi.org/10.3390/diagnostics16142265 - 20 Jul 2026

Abstract

Background: Psychiatric inpatients may be vulnerable to head trauma; however, associations among psychiatric diagnosis, trauma mechanisms, and acute trauma-related neuroimaging findings among patients requiring neurosurgical consultation remain unclear. Methods: This retrospective observational study included psychiatric inpatients referred for neurosurgical consultation after [...] Read more.

Background: Psychiatric inpatients may be vulnerable to head trauma; however, associations among psychiatric diagnosis, trauma mechanisms, and acute trauma-related neuroimaging findings among patients requiring neurosurgical consultation remain unclear. Methods: This retrospective observational study included psychiatric inpatients referred for neurosurgical consultation after head trauma at a tertiary neuropsychiatric specialty hospital between July 2022 and December 2025. Psychiatric diagnoses were grouped into psychotic, mood, substance use, organic/symptomatic, and other disorders. Trauma mechanisms were classified as falls, self-harm, assault/fight-related injuries, and other trauma types. Radiological findings were classified as trauma-related abnormalities or secondary incidental findings, including age-related changes. Associations were evaluated using chi-square tests, with false discovery rate correction applied to global and binary comparisons. Exploratory multivariable regression models were used as sensitivity analyses. Results: The cohort comprised 461 psychiatric inpatients who sustained head trauma, underwent radiological imaging, and were referred for neurosurgical consultation. Trauma mechanisms differed significantly across psychiatric diagnostic groups (χ² = 30.89, p = 0.002). Falls were the most common mechanism (189/461, 41.0%). Assault/fight-related trauma showed the clearest diagnosis-associated pattern (χ² = 19.72, p < 0.001, Cramér’s V = 0.207) and remained the only significant binary outcome after false discovery rate correction. Acute trauma-related imaging findings were observed in 35 patients (7.6%) and were not associated with psychiatric diagnosis (χ² = 6.16, p = 0.187). Calcifications were the most frequent imaging finding (191/461, 41.4%). Conclusions: In psychiatric inpatients, while head trauma patterns and neuroimaging findings have the potential to be explained by psychiatric diagnoses, they may also reflect unmeasured behavioral and clinical factors. Full article

(This article belongs to the Special Issue Traumatic Brain Injury and Associated Neurological and Neuropsychiatric Disorders: Diagnosis/Prognosis and Therapeutics)

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15 pages, 685 KB

Open AccessArticle

Prognostic Performance of the Lactate-to-Ionized Calcium Ratio for In-Hospital Mortality in Adult Major Trauma: A Retrospective Emergency Department Cohort Study

by Halil İbrahim Çimen, Mustafa Burak Sayhan, Eray Çeliktürk and Esin Seçgin Sayhan

Diagnostics 2026, 16(14), 2264; https://doi.org/10.3390/diagnostics16142264 - 20 Jul 2026

Abstract

Background/Objectives: Early identification of adult major trauma patients at high risk of death remains challenging in the emergency department. Lactate reflects tissue hypoperfusion, whereas ionized calcium contributes to coagulation and cardiovascular function. This study evaluated the prognostic performance of the lactate-to-ionized calcium [...] Read more.

Background/Objectives: Early identification of adult major trauma patients at high risk of death remains challenging in the emergency department. Lactate reflects tissue hypoperfusion, whereas ionized calcium contributes to coagulation and cardiovascular function. This study evaluated the prognostic performance of the lactate-to-ionized calcium ratio (LiCa) for in-hospital mortality and compared it with established trauma scores. Methods: This single-center retrospective cohort study included adults with major trauma, defined as an Injury Severity Score (ISS) ≥ 16, who presented to a tertiary emergency department between May 2021 and April 2023. Demographic, clinical, laboratory, and outcome data were obtained from electronic records. LiCa was calculated as lactate divided by ionized calcium using the initial arterial blood gas sample obtained within 30 min of emergency department arrival. Factors associated with mortality were examined using multivariable logistic regression. Discrimination was assessed using receiver operating characteristic analysis and compared across LiCa, ISS, and Trauma and Injury Severity Score (TRISS) models. Results: A total of 236 patients were analyzed. In-hospital mortality occurred in 49 patients (20.8%). LiCa remained associated with in-hospital mortality after adjustment (adjusted odds ratio, 1.42; 95% confidence interval, 1.23–1.62; p < 0.001). LiCa showed good discrimination in this cohort, with an area under the curve of 0.93 (95% confidence interval, 0.88–0.97), compared with 0.94 for both TRISS 1995 and TRISS 2010 and 0.85 for ISS. At an exploratory threshold of ≥12.59, LiCa yielded 82% sensitivity, 94% specificity, a positive likelihood ratio of 12.72, and a negative likelihood ratio of 0.20. Conclusions: LiCa was independently associated with in-hospital mortality and showed good discrimination within this single-center retrospective cohort. As a rapidly available blood gas-derived measure, LiCa may provide exploratory adjunctive prognostic information at presentation, but it should not be interpreted as a replacement for validated trauma scoring systems. Prospective multicenter validation is needed before routine clinical use. Full article

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

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12 pages, 734 KB

Open AccessArticle

A Multi-Provincial Clinical Evaluation of the PANBIO™ COVID-19 Antigen Rapid Test Device in South Africa

by Vidya Keshav, Lesley Scott, Anura David, Carey Pike, Linda-Gail Bekker and Wendy Stevens

Diagnostics 2026, 16(14), 2263; https://doi.org/10.3390/diagnostics16142263 - 20 Jul 2026

Abstract

Background: Rapid antigen tests were widely utilised during the COVID-19 pandemic to expand diagnostic access in resource-limited settings. However, prospective evaluations under intended-use conditions remained essential to define their role in decentralised testing strategies. Methods: We conducted a prospective multi-provincial clinical [...] Read more.

Background: Rapid antigen tests were widely utilised during the COVID-19 pandemic to expand diagnostic access in resource-limited settings. However, prospective evaluations under intended-use conditions remained essential to define their role in decentralised testing strategies. Methods: We conducted a prospective multi-provincial clinical evaluation of the Panbio™ COVID-19 Antigen Rapid Test Device in South Africa between July 2021 and January 2022. Paired nasal and nasopharyngeal swabs were collected from 609 participants across three geographically diverse South African provinces. Antigen test results were compared with standard-of-care TaqPath RT-PCR, with BD MAX™ RT-PCR included as a secondary molecular comparator. Performance was assessed by viral load, symptom status, and variant predominance periods. Results: Standard-of-care RT-PCR identified 136 positive cases (22.3% prevalence). The Panbio™ test demonstrated overall sensitivity of 80.1% (95% CI: 72–87) and specificity of 98.5% (95% CI: 97–99). Sensitivity reached 90.1% in specimens with Ct values ≤25 and 85.2% among symptomatic participants tested within seven days of onset but declined at Ct values ≥30 and in asymptomatic individuals. Performance remained consistent during Delta- and Omicron-predominant periods. Discussion: The Panbio™ RDT demonstrates high diagnostic accuracy for detecting SARS-CoV-2 in individuals with high viral load, supporting its use for rapid identification of infectious cases during transmission surges. Molecular testing remains necessary for low viral load infections and asymptomatic screening. Full article

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

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17 pages, 8883 KB

Open AccessArticle

Landmark Regression with Attention U-Net for Assessing Breast Positioning Quality in MLO Mammography View

by Nurper Denizoglu, Toygar Tanyel, Enes Can Erkan, Mustafa Ege Seker, Emine Meltem, Esma Aktufan Cerekci, Deniz Alis, Ilkay Oksuz, Ercan Karaarslan and Erkin Aribal

Diagnostics 2026, 16(14), 2262; https://doi.org/10.3390/diagnostics16142262 - 20 Jul 2026

Abstract

Background/Objectives: This study developed and evaluated a novel Attention U-Net regression model to assess MLO mammography positioning quality, comparing it against a plain U-Net regression baseline (architectural ablation) and a ResNeXt50 classification baseline. Methods: We curated 1000 patient mammograms (2000 MLO images) from [...] Read more.

Background/Objectives: This study developed and evaluated a novel Attention U-Net regression model to assess MLO mammography positioning quality, comparing it against a plain U-Net regression baseline (architectural ablation) and a ResNeXt50 classification baseline. Methods: We curated 1000 patient mammograms (2000 MLO images) from the public VinDr-Mammo dataset, with pectoral muscle line and nipple positions annotated by an expert breast radiologist. Three deep learning models were compared under a 10-fold stratified cross-validation protocol. Statistical significance was assessed with paired Wilcoxon signed-rank tests, McNemar’s test, Cochran’s Q, Wilson score confidence intervals, bootstrap confidence intervals, Holm–Bonferroni correction, and paired Cohen’s d effect sizes. Results: Against the automated PNL reference, the Attention U-Net achieved 85.5% accuracy (Wilson 95% CI [83.9%, 87.0%]), 80.2% sensitivity, and 88.7% specificity, outperforming both the plain U-Net (71.8% accuracy) and ResNeXt50 (73.7% accuracy). (Cochran’s Q p < 0.001; pairwise McNemar p < 0.001). For landmark localization, the Attention U-Net produced significantly lower errors across all five evaluated landmark and geometric measures (nipple 3.44 mm vs. 7.02 mm; perpendicular intersection 5.93 mm vs. 9.81 mm; all comparisons remained significant after Holm–Bonferroni correction). Conclusions: In this single-dataset, single-view study, an Attention U-Net landmark-regression model provided explicit landmark and PNL outputs for quantitative MLO mammography positioning assessment. The model showed improved accuracy and sensitivity compared with a plain U-Net regression baseline and a ResNeXt50 classification baseline. Full article

(This article belongs to the Special Issue Advances in Breast Imaging: Improving Detection and Diagnosis)

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19 pages, 25216 KB

Open AccessArticle

Radiomics-Based Prediction of Treatment Response in Non-Small Cell Lung Cancer Using Pre-Treatment CT Imaging Features

by Lama Almudaimeegh, Noman Nazeer, Zuhal Y. Hamd, Mohamed Alharbi, Amna Mohamed Ahmed and Muhammad Zulfiqah Sadikan

Diagnostics 2026, 16(14), 2261; https://doi.org/10.3390/diagnostics16142261 - 20 Jul 2026

Abstract

Background/Objectives: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing nearly 85% of cases worldwide. Predicting patient response before treatment, however, remains a major clinical challenge. Radiomics enables non-invasive extraction of quantitative imaging data that reflects tumor characteristics [...] Read more.

Background/Objectives: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing nearly 85% of cases worldwide. Predicting patient response before treatment, however, remains a major clinical challenge. Radiomics enables non-invasive extraction of quantitative imaging data that reflects tumor characteristics and heterogeneity. In this study, we developed and externally validated a CT-derived radiomic signature for predicting outcomes in advanced NSCLC patients treated with first-line platinum-based chemotherapy. Methods: NSCLC across three tertiary care centers were included. Tumor lesions from baseline contrast-enhanced CT scans were semi-automatically outlined using 3D Slicer software (version 5.12.2), followed by the extraction of 851 quantitative imaging biomarkers through PyRadiomics version 3.0. The extracted parameters comprised histogram-based features, morphological measurements, texture-related variables, and wavelet-derived attributes. Reliability of feature extraction was evaluated using intraclass correlation coefficient analysis, whereas LASSO regression together with stability selection was applied to identify the most relevant predictors. Predictive capability was assessed across five machine learning techniques, including logistic regression, random forest, support vector machine, gradient boosting, and multilayer perceptron models. The resulting radiomics-based composite score was then tested in an independent external validation cohort. Response to treatment was determined according to RECIST 1.1 guidelines. Results: After feature reproducibility assessment and stability screening, 421 radiomic parameters were retained for further analysis and 14 feasible parameters were selected by LASSO. There was good predictive power of the integrated model that included both radiomic and clinical features, with AUC values of 0.876, 0.849, and 0.831 in the training set, internal validation set and external validation set, respectively. The radiomic signature successfully differentiated patients according to their probability of therapeutic response. Furthermore, by using decision-curve analysis, the combined radiomics nomogram was more clinically useful than models based on clinical characteristics within clinically relevant decision-threshold ranges with greater net benefit. Conclusions: This pre-treatment CT-based radiomics signature demonstrates potential as a decision-support tool for chemotherapy-response prediction in NSCLC. However, prospective and multi-ethnic validation is required before clinical application. Based on this data, larger multi-ethnic cohorts should be considered for prospective validation. Full article

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

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14 pages, 473 KB

Open AccessArticle

Increased Risk of Thyroid Cancer in Patients with Graves’ Disease and Thyroid Nodules: A Retrospective Analysis

by Mihaela Andreea Precup, Flaviu Ionut Faur, Marco Marian, Paul Pasca, Draga-Maria Mandi, Dan Brebu, Andrei Korodi, Cosmin Mihai Burta, Amadeus Dobrescu and Ciprian Duta

Diagnostics 2026, 16(14), 2260; https://doi.org/10.3390/diagnostics16142260 - 20 Jul 2026

Abstract

Background: Graves’ disease (GD) is an autoimmune disorder frequently associated with thyroid nodules, raising concerns regarding malignancy risk. However, reported cancer prevalence varies widely, and data from Eastern European populations remain limited. This study aimed to evaluate the risk of thyroid cancer in [...] Read more.

Background: Graves’ disease (GD) is an autoimmune disorder frequently associated with thyroid nodules, raising concerns regarding malignancy risk. However, reported cancer prevalence varies widely, and data from Eastern European populations remain limited. This study aimed to evaluate the risk of thyroid cancer in GD patients and to identify clinical predictors of malignancy. Methods: We conducted a retrospective cohort study including 168 patients diagnosed with GD between 2018 and 2022 at a tertiary referral center. Clinical, ultrasonographic, and histopathological data were analyzed. Associations between thyroid nodules and malignancy were assessed using chi-square tests and logistic regression analysis. Results: Thyroid nodules were identified in a substantial proportion of GD patients, and among patients with thyroid nodules who underwent thyroidectomy, thyroid carcinoma was confirmed by histopathological examination in 11 of 42 cases (26.2%). The presence of nodules was significantly associated with malignancy (OR = 4.337, 95% CI: 1.528–7.146, p < 0.001). Increasing age was independently associated with higher cancer risk (r = 0.221, p = 0.004). Papillary thyroid carcinoma (PTC) was the predominant histological subtype, most commonly presenting as early-stage disease (pT1aNxR0). Conclusions: Thyroid nodules were significantly associated with thyroid malignancy in patients with Graves’ disease. In this tertiary referral cohort, papillary thyroid carcinoma was the predominant histological subtype, supporting careful ultrasound evaluation and appropriate cytological assessment of thyroid nodules. Full article

(This article belongs to the Special Issue State of the Art in the Diagnosis and Management of Endocrine Tumors)

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20 pages, 9200 KB

Open AccessArticle

A Multilevel Deep Learning Model for Automated Brain Tumor Segmentation Using Magnetic Resonance Images

by Aneesh S. Perumprath, Kulandairaj Martin Sagayam, Syed Immamul Ansarullah, Shafat Khan, Sami Alshmrany, Farhan Amin, Isabel de la Torre Díez, Mirtha Silvana Garat de Marin and Eduardo Silva Alvarado

Diagnostics 2026, 16(14), 2259; https://doi.org/10.3390/diagnostics16142259 - 20 Jul 2026

Abstract

Background/Objectives: Brain tumor segmentation from magnetic resonance imaging (MRI) plays an important role in clinical assessment and treatment planning. However, accurate segmentation remains challenging because of the complex anatomical structure of the brain, variations in tumor size and shape, and the imbalance between [...] Read more.

Background/Objectives: Brain tumor segmentation from magnetic resonance imaging (MRI) plays an important role in clinical assessment and treatment planning. However, accurate segmentation remains challenging because of the complex anatomical structure of the brain, variations in tumor size and shape, and the imbalance between tumor and non-tumor regions in MRI datasets. These challenges highlight the need for reliable automated segmentation methods. Methods: This study proposes a multilevel deep learning model for automated brain tumor segmentation using MRI images. The BraTS dataset was used for model development and evaluation. To address class imbalance, a modified Synthetic Minority Oversampling Technique (SMOTE) was incorporated during preprocessing. A Multilevel Architecture-Based Modified U-Net was then employed to learn multiscale spatial features and generate pixel-wise tumor segmentation. The proposed framework was evaluated using the Dice coefficient, Jaccard coefficient, Matthews Correlation Coefficient (MCC), and accuracy. Results: The experimental results demonstrate that the proposed model consistently outperformed the Berkeley Wavelet Transform (BWT)-based method and the conventional U-Net across different tumor grades. Higher Dice, Jaccard, and MCC values indicate improved agreement between the predicted segmentation and the expert-annotated ground truth masks, demonstrating more accurate and consistent tumor delineation. Conclusions: The proposed multilevel deep learning model provides an effective framework for automated brain tumor segmentation from MRI images. By combining imbalance-aware preprocessing with a lightweight Modified U-Net architecture, the proposed method improves segmentation performance while maintaining a relatively simple network design. Future work will focus on validating the proposed framework using external clinical datasets and comparing it with recent state-of-the-art segmentation models. Full article

(This article belongs to the Special Issue 3rd Edition: AI/ML-Based Medical Image Processing and Analysis)

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13 pages, 1644 KB

Open AccessArticle

Risk Factors for Acute Respiratory Distress Syndrome in Sepsis Caused by Peptic Ulcer Perforation: A Retrospective Study

by Yavuz Selim Kahraman, Veysel Garani Soylu, Öztürk Taşkın and Ufuk Demir

Diagnostics 2026, 16(14), 2258; https://doi.org/10.3390/diagnostics16142258 - 20 Jul 2026

Abstract

Background/Objectives: Our study aimed to identify risk factors for the development of ARDS (acute respiratory distress syndrome) in patients with sepsis resulting from peptic ulcer perforation. Methods: Between January 2018 and December 2025, patients aged 18 years and older who underwent open surgery [...] Read more.

Background/Objectives: Our study aimed to identify risk factors for the development of ARDS (acute respiratory distress syndrome) in patients with sepsis resulting from peptic ulcer perforation. Methods: Between January 2018 and December 2025, patients aged 18 years and older who underwent open surgery for peptic ulcer perforation and were diagnosed with sepsis due to intra-abdominal infection related to peptic ulcer perforation during postoperative follow-up or hospitalization were included in the study. Daily ARDS screening was performed within 7 days of sepsis diagnosis. Patients were divided into groups with and without ARDS. Laboratory values were recorded within the first 24 h after sepsis diagnosis, and APACHE II score, SOFA score, NEWS, and SAPS II were calculated based on these values and the patient’s clinical condition. Results: The SOFA score showed the highest discriminative ability, with an AUC of 0.710 (95% CI: 0.619–0.794) at a cutoff of 9.0, representing 54.2% sensitivity and 83.1% specificity. Albumin level showed an AUC of 0.654 (95% CI: 0.560–0.748) at a cutoff of 2.40 g/dL; its specificity was high (85.1%), but its sensitivity was relatively low (41.7%). CAR showed moderate predictive performance with an AUC of 0.627 (95% CI: 0.522–0.730) at a cutoff of 61.11, representing 60.4% sensitivity and 72.1% specificity. The combined model demonstrated the best predictive performance with an AUC of 0.727 (95% CI: 0.635–0.820), 70.8% sensitivity, and 72.7% specificity. Conclusions: SOFA score demonstrated the best overall clinical applicability for early ARDS risk stratification, while both SOFA score and APACHE II score showed independent associations with ARDS in separate multivariable models. Full article

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

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13 pages, 1158 KB

Open AccessArticle

Decoding the Ektacytometric Landscape of Hereditary Spherocytosis: Insights from 204 Cases

by Anna Zaninoni, Elisa Fermo, Cristina Vercellati, Anna Paola Marcello, Dario Consonni, Nayssen Naouara, Bruno Fattizzo, Wilma Barcellini and Paola Bianchi

Diagnostics 2026, 16(14), 2257; https://doi.org/10.3390/diagnostics16142257 - 20 Jul 2026

Abstract

Background: Hereditary Spherocytosis (HS), the most common congenital hemolytic anemia, is characterized by highly heterogeneous clinical manifestations with variable hemolytic anemia, jaundice, reticulocytosis, splenomegaly, and gallstones. The ektacytometric analysis is considered a gold standard tool for HS diagnosis. Two distinct profiles may [...] Read more.

Background: Hereditary Spherocytosis (HS), the most common congenital hemolytic anemia, is characterized by highly heterogeneous clinical manifestations with variable hemolytic anemia, jaundice, reticulocytosis, splenomegaly, and gallstones. The ektacytometric analysis is considered a gold standard tool for HS diagnosis. Two distinct profiles may be observed: the typical bell-shaped profile (HS1) and a right-shifted curve (HS2); nonetheless, the clinical and biochemical significance of these differences, and their correlation with the clinical phenotype of HS remain poorly understood. Methods: We analyzed a large cohort of non-splenectomised HS patients, focusing on their ektacytometric curves and their hematologic and biochemical features. Results: We found that HS2 patients were significantly younger and showed a more severe anemia compared to HS1; in particular, HS2 patients had lower Hb levels and MCHC values, and higher RDW. Interestingly, only in the HS1 group, we observed a negative correlation between MCHC and all osmoscan parameters related to osmolality (Omin, Ohyper, and Omax). Conclusions: All the results indicate that HS may be characterized by two typical shapes of the ektacytometric curve, where HS2 profiles are associated with more severe and young patients, and that in the more HS severe cases red cells show a lower density. Full article

(This article belongs to the Special Issue Advances in Hematology Laboratory—2nd Edition)

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13 pages, 293 KB

Open AccessArticle

Reliability, Validity, and Clinical Interrelationships of Lower-Extremity Screening Measures in College Athletes

by Aylin Ardalı, Deren Kalfaoğlu, Melih Köksal and Ezgi Tuna Erdoğan

Diagnostics 2026, 16(14), 2256; https://doi.org/10.3390/diagnostics16142256 - 19 Jul 2026

Abstract

Background/Objectives: Modifiable intrinsic factors such as foot posture, hallux mobility, dynamic balance, and body mass index (BMI) are widely assessed in athletic screening, but their reliability and interrelationships remain unclear. The aim of the study was to evaluate the reliability of foot posture, [...] Read more.

Background/Objectives: Modifiable intrinsic factors such as foot posture, hallux mobility, dynamic balance, and body mass index (BMI) are widely assessed in athletic screening, but their reliability and interrelationships remain unclear. The aim of the study was to evaluate the reliability of foot posture, hallux mobility, dynamic balance, Q-angle, and navicular drop measures in collegiate athletes and to examine the relationships among these measures and BMI. The concurrent, discriminant, and predictive validity of the Foot Posture Index (FPI6) relative to the navicular drop test (NDT) was also assessed. Methods: Fifty-nine athletes participated: 10 in a reliability subsample and 49 in a separate validity subsample. Assessments included BMI, FPI-6, hallux valgus angle, hallux dorsiflexion, Y Balance Test (YBT), Q-angle, and NDT. Reliability was assessed using intraclass correlation coefficients (ICCs). Associations among measures and FPI6-NDT concurrent validity were examined using Spearman correlations and non-parametric group comparisons. Classification performance indices relative to NDT were calculated for FPI-6. Results: All measures demonstrated good to excellent reliability (ICC = 0.81–0.99). FPI-6 showed a strong concurrent association with NDT (rho = 0.735). More pronated foot posture was moderately associated with lower YBT performance and reduced hallux dorsiflexion (rho = −0.301 to −0.635). Higher BMI was associated with greater navicular drop and lower dynamic balance (rho = 0.301 to −0.433). FPI-6 showed high classification agreement with NDT-defined foot posture groups (specificity 96.9%; overall agreement 91.8%). Conclusions: Lower extremity alignment, hallux mobility, dynamic balance, and BMI showed modest interrelationships. FPI-6 demonstrated strong concurrent validity and high classification agreement relative to NDT, supporting practical screening use. Given the correlational nature of the findings, interpretations should remain cautious, and larger multimodal studies are warranted. Full article

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

39 pages, 1211 KB

Open AccessReview

Three-Dimensional Left Atrial Geometry in Atrial Fibrillation: Imaging Biomarkers, Substrate Phenotyping, and Ablation Outcome Prediction

by Paschalis Karakasis, Panagiotis Theofilis, Panagiotis Stachteas, Konstantinos Grigoriou, Panagiotis Iliakis, Athina Nasoufidou, Panayotis K. Vlachakis, Nikolaos Ktenopoulos, Anastasios Apostolos, Theodoros Karamitsos, Antonios P. Antoniadis and Nikolaos Fragakis

Diagnostics 2026, 16(14), 2255; https://doi.org/10.3390/diagnostics16142255 - 19 Jul 2026

Abstract

Assessment of left atrial remodeling in atrial fibrillation (AF) has traditionally relied on anteroposterior diameter, left atrial volume (LAV), and indexed left atrial volume (LAVI). Although these measures remain clinically useful, they reduce a complex, asymmetric, and anatomically constrained chamber to scalar descriptors [...] Read more.

Assessment of left atrial remodeling in atrial fibrillation (AF) has traditionally relied on anteroposterior diameter, left atrial volume (LAV), and indexed left atrial volume (LAVI). Although these measures remain clinically useful, they reduce a complex, asymmetric, and anatomically constrained chamber to scalar descriptors and therefore cannot fully capture the spatial substrate that underlies AF persistence, thromboembolic risk, or arrhythmia recurrence after catheter ablation. Three-dimensional left atrial reconstruction provides a more refined framework by preserving chamber shape, regional deformation, pulmonary vein (PV) orientation, left atrial appendage (LAA) geometry, posterior wall and roof configuration, left lateral ridge anatomy, wall-thickness heterogeneity, and computational surface features. In this review, we examine how three-dimensional left atrial geometry can extend conventional remodeling assessment from measurement of atrial size toward imaging-based substrate characterization. We discuss the relative strengths and limitations of computed tomography (CT), cardiovascular magnetic resonance (CMR), three-dimensional echocardiography, and electroanatomic mapping (EAM), and summarize key geometry-derived metrics, including LAV, LAVI, left atrial sphericity, asymmetry index, atrial eccentricity index, PV anatomy, LAA morphology, posterior wall geometry, wall thickness, radiomics, and artificial intelligence (AI)-derived shape descriptors. We further synthesize evidence linking geometric remodeling with atrial cardiomyopathy, mechanical dysfunction, fibrosis, low-voltage substrate, and catheter ablation outcomes. The clinical relevance of three-dimensional left atrial geometry may be further redefined by pulsed field ablation (PFA), whose non-thermal lesion biology and tissue selectivity may modify predictors of recurrence established in radiofrequency and cryoballoon cohorts. Finally, we outline the need for standardized segmentation, harmonized metric definitions, prospective multicenter validation, and integration with AI, digital twin modeling, biomarkers, EAM data, and wearable-derived AF burden. Three-dimensional left atrial geometry is not yet a standalone determinant of ablation strategy, but it may become a central component of individualized atrial phenotyping and rhythm-control decision-making. Full article

(This article belongs to the Special Issue Interdisciplinary Approaches to Improve Cardiovascular Outcomes)

13 pages, 529 KB

Open AccessArticle

Predictive Accuracy of Serum N-Terminal Pro-B-Type Natriuretic Peptide Alone and in Combination with Respiratory Function Tests to Identify Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH)

by Zoe Brown, Dylan Hansen, Laura Ross, Wendy Stevens, Kathleen Morrisroe, Alannah Quinlivan, Maryam Tabesh, Gene-Siew Ngian, Diane Apostolopoulos, Joanne Sahhar, Jennifer G. Walker, Lauren Host, Susanna Proudman and Mandana Nikpour

Diagnostics 2026, 16(14), 2254; https://doi.org/10.3390/diagnostics16142254 - 19 Jul 2026

Abstract

Background/Objectives: Pulmonary arterial hypertension (PAH) occurs in >12% of systemic sclerosis (SSc) patients and has a high mortality. Annual screening for all SSc patients is the standard of care and can include spirometry (RFT), serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and echocardiography [...] Read more.

Background/Objectives: Pulmonary arterial hypertension (PAH) occurs in >12% of systemic sclerosis (SSc) patients and has a high mortality. Annual screening for all SSc patients is the standard of care and can include spirometry (RFT), serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and echocardiography (TTE). We sought to evaluate the accuracy of NT-proBNP alone to screen for SSc-PAH. Methods: We defined groups as low, intermediate and high risk of PAH according to RFT, TTE and RHC (right heart catheter) parameters. NT-proBNP thresholds predictive of risk group were defined, and ROC curves were used to evaluate the predictive accuracy of the calculated cut-points to diagnose SSc-PAH within the following 12 months. Results: A total of 820 SSc patients had NT-proBNP recorded 12 months prior to RHC, or if no RHC had been performed, within 12 months of the most recently recorded annual visit. The majority (335, 40.85%) were assigned to low risk of PAH, 189 (23.05%) to intermediate risk and 176 (21.46%) to high risk. NT-proBNP level < 122.9 ng/L defined the low-risk group, 122.9–186.6 ng/L defined the intermediate risk and >186.6 ng/L defined the high risk. NT-proBNP ≥210 ng/L with RFT (the ‘ASIG algorithm’) had the highest predictive accuracy, with sensitivity of 86.75% (77.52–93.19%), specificity of 60.71% (58.52–62.87%), PPV of 8.47% (6.69–10.55%), NPV of 99.09% (98.38–99.55%) and AUC of 0.74 (0.70–0.78). NT-proBNP ≥ 210 ng/L alone had sensitivity of 67.05% (56.21–76.70), specificity of 71.91% (70.03–73.72), PPV of 8.25% (6.34–10.52), NPV of 98.30% (97.57–98.86) and AUC of 0.69 (0.64–0.74). NT-proBNP thresholds associated with the three defined risk groups performed similarly overall. Conclusions: NT-proBNP alone, compared to the ASIG algorithm, had a slight reduction in NPV and AUC to predict PAH within 12 months. When NT-proBNP is ≥210 ng/L, the NPV remains high (98.0%). Full article

(This article belongs to the Special Issue Advanced Diagnostic Approaches in Cardiovascular Diseases: From Imaging to Biomarkers)

15 pages, 3970 KB

Open AccessArticle

Association of Fetal Intrahepatic Umbilical–Portal Anastomosis Type with Late-Onset Fetal Growth Restriction and Neonatal Outcomes

by Kubilay Çanga, Recep Taha Ağaoğlu, Özgür Volkan Akbulut, Mustafa Bağcı, Emel Özalp, Muhammed Alp Özdemir, Yüksel Oğuz and Kadriye Yakut Yücel

Diagnostics 2026, 16(14), 2253; https://doi.org/10.3390/diagnostics16142253 - 19 Jul 2026

Abstract

Objective: To evaluate whether fetal intrahepatic umbilical–portal anastomosis type is associated with late-onset fetal growth restriction (FGR) and adverse neonatal outcomes. Methods: This prospective, single-center case–control study included 160 singleton pregnancies in the third trimester: 80 with late-onset FGR defined according to Delphi [...] Read more.

Objective: To evaluate whether fetal intrahepatic umbilical–portal anastomosis type is associated with late-onset fetal growth restriction (FGR) and adverse neonatal outcomes. Methods: This prospective, single-center case–control study included 160 singleton pregnancies in the third trimester: 80 with late-onset FGR defined according to Delphi consensus criteria and 80 appropriate-for-gestational-age (AGA) controls. Umbilical–portal anastomosis was assessed by ultrasound and classified as T-shaped, X-shaped, or H-shaped. Maternal, sonographic, obstetric, and neonatal data were recorded. Multivariable logistic regression evaluated associations with FGR, and Firth’s penalized regression assessed composite adverse perinatal outcome (CAPO) within the FGR group. Results: X-shaped anastomosis predominated in FGR (55.0%; T-shaped, 26.3%; H-shaped, 18.8%), whereas T-shaped was most common in controls (61.3%; X-shaped, 23.8%; H-shaped, 15.0%). FGR cases showed higher umbilical artery pulsatility index, lower middle cerebral artery pulsatility index and cerebroplacental ratio, earlier delivery, lower birth weight, and higher rates of NICU (neonatal intensive care unit) admission, transient tachypnea of the newborn, and CAPO (35% vs. 15%). Both X-shaped and H-shaped types were independently associated with FGR, with a stronger effect for X-shaped (adjusted odds ratio [aOR], 5.27 vs. 2.85). Predicted probabilities increased stepwise from T-shaped to H-shaped to X-shaped (30.3%, 55.3%, and 69.6%). Within the FGR group, only X-shaped anastomosis was independently associated with CAPO, whereas Doppler indices were not discriminatory. Conclusions: X-shaped fetal intrahepatic umbilical–portal anastomosis was independently associated with both late-onset FGR and adverse neonatal outcome. Intrahepatic vascular configuration may provide additional value beyond conventional fetal biometry and arterial Doppler in risk stratification. Full article

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

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15 pages, 676 KB

Open AccessArticle

Multiplex-PCR Identification of Positive Blood Cultures: Pathogen Epidemiology, Resistance Determinants, and the Economic and Interpretive Cost of Qualitative Rapid Diagnosis

by Laura Lupo, Ilaria Serafini, Daniela Chirizzi, Angela Spedicato, Gabriele Bianco, Daniele Pisanò, Maria Rita Orsi, Giovanni Moschettini, Marcella Marullo, Angelo Sorge, Rosanna Bruno, Camilla Panico, Silvana Arnesano, Antonella Simone, Luciana Corciulo, Antonella Pico, Claudia Pagano, Letizia Fulceri, Giulia Apruzzi, Anna De Filippis, Massimiliano Galdiero and Francesco Broccolo Show full author list Hide full author list

Diagnostics 2026, 16(14), 2252; https://doi.org/10.3390/diagnostics16142252 - 18 Jul 2026

Abstract

Background/Objectives: Bloodstream infections (BSIs) carry high mortality, and any delay in initiating optimal antimicrobial therapy worsens outcomes. Syndromic multiplex-PCR panels applied to signal-positive blood cultures markedly shorten time-to-identification but are expensive and report results in a strictly qualitative format. We describe twenty-two months [...] Read more.

Background/Objectives: Bloodstream infections (BSIs) carry high mortality, and any delay in initiating optimal antimicrobial therapy worsens outcomes. Syndromic multiplex-PCR panels applied to signal-positive blood cultures markedly shorten time-to-identification but are expensive and report results in a strictly qualitative format. We describe twenty-two months of real-world BioFire FilmArray Blood Culture Identification 2 (BCID2) testing in a southern Italian hospital, focusing on pathogen epidemiology, resistance-gene detection, and the economic and interpretive trade-offs of the assay. Methods: We retrospectively reviewed all BCID2 runs performed on signal-positive blood-culture bottles at P.O. “Vito Fazzi” (ASL Lecce) from July 2024 to April 2026. Each run was classified as single-pathogen-positive, polymicrobial (co-infection)-positive, or negative (no on-panel target). Resistance determinants were tabulated by year and by presumptive carrier. A direct-cost analysis was performed at a reagent cost of €250 per test. Results: Of 498 runs, 401 (80.5%) yielded at least one on-panel target (330 single-pathogen, 71 polymicrobial), whereas 97 (19.5%) were negative. Among 526 organism detections, Gram-positive (48.9%) and Gram-negative (45.8%) bacteria predominated; Staphylococcus spp., Escherichia coli and the Klebsiella pneumoniae group were most frequent. Resistance determinants (n = 244) were dominated by mecA/C, CTX-M and KPC. Co-infections (17.7% of positives) frequently prevented unambiguous attribution of a resistance gene to a specific co-detected organism. Total reagent expenditure was €124,500, of which €24,250 (19.5%) was spent on negative results. Conclusions: BCID2 delivered rapid, broad pathogen and resistance-gene detection in a high-resistance setting. Its qualitative-only output, the difficulty of attributing a resistance gene to a specific organism in polymicrobial samples, and the cost of negative results nonetheless argue for diagnostic-stewardship gating, semiquantitative reporting, and local validation of complementary and lower-cost assays. Full article

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

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3 pages, 1600 KB

Open AccessInteresting Images

Upregulation of Somatostatin Receptor Expression in Lactating Breast Shown in ^99mTc-HYNIC-TOC Scintigraphy

by Mengyao Jia, Jie Feng and Yaping Luo

Diagnostics 2026, 16(14), 2251; https://doi.org/10.3390/diagnostics16142251 - 18 Jul 2026

Abstract

A 31-year-old female patient with a 4-year history of multiple endocrine neoplasia type 1 (MEN1) presented with abdominal pain and weight loss that she had been experiencing over the past 6 months. Somatostatin receptor (SSTR) scintigraphy using 99mTc-HYNIC-TOC revealed increased uptake in the [...] Read more.

A 31-year-old female patient with a 4-year history of multiple endocrine neoplasia type 1 (MEN1) presented with abdominal pain and weight loss that she had been experiencing over the past 6 months. Somatostatin receptor (SSTR) scintigraphy using 99mTc-HYNIC-TOC revealed increased uptake in the known pancreatic neuroendocrine tumor as well as diffuse increased uptake in bilateral lactating breasts. This case highlights physiological upregulation of somatostatin receptor expression in a lactating breast. Full article

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

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19 pages, 9933 KB

Open AccessArticle

Integrated Bioinformatics and Experimental Validation Reveal the Diagnostic and Prognostic Value of SMDT1 in Thyroid Carcinoma

by Tenghong Liu, Hongyi Wu, Zhijun Chen and Wenxin Zhao

Diagnostics 2026, 16(14), 2250; https://doi.org/10.3390/diagnostics16142250 - 18 Jul 2026

Abstract

Background: Thyroid carcinoma (THCA), especially papillary thyroid carcinoma (PTC), remains clinically challenging because recurrence and metastasis occur in a subset of patients. SMDT1 is an essential regulator of the mitochondrial calcium uniporter complex that may influence tumor progression, but its role in [...] Read more.

Background: Thyroid carcinoma (THCA), especially papillary thyroid carcinoma (PTC), remains clinically challenging because recurrence and metastasis occur in a subset of patients. SMDT1 is an essential regulator of the mitochondrial calcium uniporter complex that may influence tumor progression, but its role in thyroid carcinoma is unclear. This study investigated the expression, clinical significance, and biological functions of SMDT1 in thyroid carcinoma. Methods: Public databases were used to analyze SMDT1 expression, diagnostic value, prognostic relevance, co-expression networks, functional enrichment, protein interactions, and immune infiltration. SMDT1 expression was validated in 50 paired PTC and adjacent non-tumorous tissues. In vitro SMDT1 overexpression was performed in PTC cell lines, followed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB), CCK-8, colony formation, wound healing, and transwell assays. Results:SMDT1 was significantly downregulated in thyroid carcinoma tissues, PTC tissues, and PTC cell lines. Low SMDT1 expression was associated with lymph node metastasis and shorter disease-free survival. Functional analyses linked SMDT1 with mitochondrial calcium transport, oxidative phosphorylation, apoptosis, cellular senescence, and immune infiltration, including CD8⁺ T cells and activated NK cells. SMDT1 overexpression significantly suppressed PTC cell proliferation, colony formation, migration, and invasion. Conclusions:SMDT1 may function as a tumor suppressor in thyroid carcinoma and has potential diagnostic and prognostic value. Its effects may involve mitochondrial calcium homeostasis, metabolic regulation, and immune microenvironment remodeling. Full article

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

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13 pages, 1871 KB

Open AccessArticle

Malignancy Risk Within Hyperfunctioning Thyroid Nodules: Clinicopathologic Features and Diagnostic Implications

by Pang-Jui Huang, Shun-Yu Chi, Shun-Chen Huang, Yen-Hsiang Chang and Chen-Kai Chou

Diagnostics 2026, 16(14), 2249; https://doi.org/10.3390/diagnostics16142249 - 18 Jul 2026

Abstract

Background/Objectives: Hyperfunctioning thyroid nodules are generally considered to have a low malignancy risk, but data on genuine hyperfunctioning thyroid neoplasms remain limited. This study aimed to characterize the clinicopathologic features and diagnostic implications of true hyperfunctioning thyroid neoplasms through lesion-level imaging-pathologic correlation [...] Read more.

Background/Objectives: Hyperfunctioning thyroid nodules are generally considered to have a low malignancy risk, but data on genuine hyperfunctioning thyroid neoplasms remain limited. This study aimed to characterize the clinicopathologic features and diagnostic implications of true hyperfunctioning thyroid neoplasms through lesion-level imaging-pathologic correlation and to estimate their observed frequency within a surgically treated cohort. Methods: We retrospectively reviewed 82 hyperthyroid patients at our institution with thyroid scintigraphy suggestive of solitary or multiple toxic nodules between 2014 and 2024; 25 underwent thyroidectomy. True hyperfunctioning thyroid neoplasms were defined by lesion-level imaging-pathologic correlation. Results: Among the 25 surgically treated patients, seven had confirmed hyperfunctioning carcinoma or tumors of uncertain malignant potential (UMP) (28.0%; 95% CI, 14.1–47.8%). When referenced against the full scintigraphic cohort of 82 patients, of whom only 30.5% underwent surgery, the observed rate was 8.5% (95% CI, 4.2–16.6%); however, this figure should be interpreted with caution given the inherent surgical selection bias. Four patients had overt carcinomas. The remaining three patients had UMPs. In nodule-based analysis, hyperfunctioning neoplasms were significantly larger than coexisting tumors (5.0 ± 2.8 vs. 0.8 ± 0.7 cm, p = 0.007) and more often follicular-patterned (85.7% vs. 27.3%; RR, 3.14; 95% CI, 1.14 to 8.64; p = 0.0498). Conclusions: These findings indicate that hyperfunctioning status does not definitively exclude malignancy, while also emphasizing that the absolute malignancy frequency in unselected hyperthyroid populations remains uncertain. Full article

(This article belongs to the Special Issue Thyroid Cancer Diagnosis and Management: Current Status, Challenges, and Future Directions)

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