Diagnostics

15 pages, 233 KB

Open AccessArticle

Clinical Utility of a Targeted Next-Generation Sequencing Panel for Inherited Platelet Disorders in Children

by Dilek Kaçar, Mustafa Altan, Turan Bayhan, Said Furkan Yıldırım, Fatma Burçin Kurtipek, Özlem Arman Bilir, Namık Yaşar Özbek and Neşe Yaralı

Diagnostics 2025, 15(17), 2210; https://doi.org/10.3390/diagnostics15172210 (registering DOI) - 30 Aug 2025

Abstract

Background/Objectives: Inherited platelet disorders (IPDs) are diverse conditions characterized by abnormalities in platelet count and function. Next-Generation Sequencing (NGS) shows promise as a diagnostic tool in the diagnosis of IPDs. This study aims to assess the clinical value and limitations of using [...] Read more.

Background/Objectives: Inherited platelet disorders (IPDs) are diverse conditions characterized by abnormalities in platelet count and function. Next-Generation Sequencing (NGS) shows promise as a diagnostic tool in the diagnosis of IPDs. This study aims to assess the clinical value and limitations of using a targeted NGS panel in diagnosing children with suspected IPDs. Methods: We conducted a retrospective study of 93 children evaluated for suspected IPDs. A targeted NGS panel of 14 IPD-associated genes (RUNX1, WAS, ADAMTS13, ANKRD26, CYCS, GATA1, GP1BA, GB1BB, GP9, ITGA2B, ITGB3, MASTL, MPL, MYH9) was performed. Results: Genetic variants were identified in 30 patients (32.3% of the cohort). A total of 37 variants, of which 15 (40.5%) were novel, were found across 11 of the 14 genes on the panel (all except MPL, CYCS, and RUNX1). Variants were most frequently found in ITGB3 (18.9% of variants), GP1BA (16.2%), and ADAMTS13 (16.2%) genes. The majority of variants (64.9%) were classified as variants of uncertain significance (VUS), followed by likely pathogenic (LP) (27%) and pathogenic (8.1%) variants. Most variants were in a heterozygous state (73%). Specific cases highlighted complex genetic scenarios, such as co-occurring variants, and the identification of pathogenic and LP variants in patients initially presenting with immune thrombocytopenia. Conclusions: NGS helps to identify genetic causes, assess risk, manage, and provide genetic counseling in the management of IPDs. However, the prevalence of VUS underscores the need for a multidisciplinary approach to evaluate NGS results accurately. Full article

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

22 pages, 1382 KB

Open AccessArticle

Decoding Diagnostic Delay in COPD: An Integrative Analysis of Missed Opportunities, Clinical Risk Profiles, and Targeted Detection Strategies in Primary Care

by Juan Luis Rodríguez Hermosa, Soha Esmaili, Iman Esmaili, Myriam Calle Rubio and Carla García Novoa

Diagnostics 2025, 15(17), 2209; https://doi.org/10.3390/diagnostics15172209 (registering DOI) - 30 Aug 2025

Abstract

Background: Delayed diagnosis of Chronic Obstructive Pulmonary Disease (COPD) in primary care is common and contributes to preventable morbidity. A deeper understanding of pre-diagnostic patterns is needed to develop targeted detection strategies. We aimed to characterize diagnostic delay and missed diagnostic opportunities [...] Read more.

Background: Delayed diagnosis of Chronic Obstructive Pulmonary Disease (COPD) in primary care is common and contributes to preventable morbidity. A deeper understanding of pre-diagnostic patterns is needed to develop targeted detection strategies. We aimed to characterize diagnostic delay and missed diagnostic opportunities (MDOs) and identify high-risk clinical profiles. Methods: We conducted a retrospective cohort study of 167 patients newly diagnosed with COPD in primary care centers in Madrid, Spain. Healthcare utilization in the 12 months preceding diagnosis was analyzed. Multivariable logistic regression was used to identify predictors of MDOs, and K-means clustering was used to identify patient phenotypes. Results: Diagnostic delay (>30 days) was present in 45.5% of patients, and MDOs in 47.3%. MDO-positive patients had significantly worse lung function (mean FEV₁: 1577 vs. 1898 mL, p = 0.008), greater symptom burden (CAT score ≥ 10: 79.7% vs. 59.1%, p = 0.003), and more frequent pre-diagnostic exacerbations (mean: 1.24 vs. 0.71, p = 0.032). After multivariable adjustment, diagnostic delay remained a powerful independent predictor of MDOs (OR 10.25, 95% CI 4.39–24.88; p < 0.001). Cluster analysis identified three distinct clinical phenotypes: ‘Paucisymptomatic–Preserved’, ‘Frequent Attenders/High-Risk’, and ‘Silent Decliners’. Conclusions: The pre-diagnostic period in COPD is a dynamic window of detectable, and potentially preventable, clinical deterioration driven by diagnostic inertia. The identification of distinct patient phenotypes suggests that a proactive, stratified, and personalized approach, rather than a one-size-fits-all strategy, is required to improve early diagnosis in primary care. Full article

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

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13 pages, 3117 KB

Open AccessArticle

Functioning and Safety of the Non-Invasive Corneal Esthesiometer Brill: A Multicenter Study

by Concepción Renedo Laguna, Carmen Gómez Martín, Javier Lozano-Sanroma, José Manuel Benítez del Castillo, Jesús Montero Iruzubieta, Salvador García Delpech and Jesús Merayo-Lloves

Diagnostics 2025, 15(17), 2208; https://doi.org/10.3390/diagnostics15172208 (registering DOI) - 30 Aug 2025

Abstract

Background/Objectives: Corneal sensitivity can be decreased by several ocular conditions, including dry eye and refractive surgery, which can lead to ocular epithelial lesions. This decrease can be detected by esthesiometry. The main objective of this study was to evaluate the performance, safety, [...] Read more.

Background/Objectives: Corneal sensitivity can be decreased by several ocular conditions, including dry eye and refractive surgery, which can lead to ocular epithelial lesions. This decrease can be detected by esthesiometry. The main objective of this study was to evaluate the performance, safety, and efficacy of the Corneal Esthesiometer Brill in healthy subjects without ocular pathologies. Methods: A controlled, randomized, prospective, multicenter pilot clinical study was conducted in adult patients with healthy eyes. Corneal sensitivity measurements were made three times for one eye randomly selected to obtain the corneal sensitivity reference ranges. Additionally, one more measurement was taken after the application of a topical anesthetic. An intra- and inter-observer analysis was performed to assess user dependence, and the last measurement was taken after ocular topical anesthesia to evaluate the device’s sensitivity in detecting corneal sensitivity loss. Results: Ninety-one volunteers were included with a mean age of 25 (SD 3.46, range 18–30), and fifty-eight (63.7%) were female. Corneal sensitivity reference levels ranged from level 2 (3–4 mbar) to level 3 (4–5 mbar). Intra- and inter-observer measurement differences on the same subject without anesthesia were not statistically significant. Corneal pressure before and after local ocular anesthesia had statistically significant differences (p < 0.0001). Conclusions: The Corneal Esthesiometer Brill yielded consistent and reproducible measurements in young volunteers with healthy eyes, enabling objective, observer-independent use and facilitating the detection of significant loss of sensitivity. Full article

(This article belongs to the Special Issue Advances in Diagnostics of the Cornea, Cataract and Refractive Surgery)

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17 pages, 629 KB

Open AccessArticle

In Vivo Confocal Microscopy of the Cornea in Diagnosing Small Fibre Neuropathy: A Cross-Sectional Observational Study

by David Petrovič, Ajla Mujnović, Adela Hammami, Tjaša Krašovec, Mojca Kirbiš and Spela Stunf Pukl

Diagnostics 2025, 15(17), 2207; https://doi.org/10.3390/diagnostics15172207 (registering DOI) - 30 Aug 2025

Abstract

Objectives: The aim of this study was to assess the accuracy of corneal in vivo confocal microscopy (IVCM) in the diagnostic process of small fibre neuropathy (SFN) compared to skin biopsy. Methods: This cross-sectional observational study was performed at the Eye Hospital and [...] Read more.

Objectives: The aim of this study was to assess the accuracy of corneal in vivo confocal microscopy (IVCM) in the diagnostic process of small fibre neuropathy (SFN) compared to skin biopsy. Methods: This cross-sectional observational study was performed at the Eye Hospital and Institute of Neurophysiology, University Medical Centre Ljubljana, and included 35 patients with a clinical picture of SFN. All patients underwent a neurological exam that included an SFN questionnaire, standard skin biopsy, and ophthalmological assessment, including corneal IVCM. Results: Skin biopsy confirmed SFN in 14/35 patients (40%). These patients had a significantly shorter corneal nerve fibre length (CNFL) compared to those with negative biopsy (13.67 ± 2.99 mm/mm² vs. 16.27 ± 3.54 mm/mm², p = 0.030), as well as reduced corneal nerve branch density (CNBD) (36.68 ± 14.68 branches/mm² vs. 48.81 ± 17.83 branches/mm², p = 0.042). CNFL reduction below the 5th percentile was proven in 13/35 patients, yielding 64.3% sensitivity (95% CI: 35.1–87.2%) and 80.9% specificity (95% CI: 58.1–94.6%) compared to skin biopsy. In idiopathic SFN, negative IVCM results aligned with negative biopsies in 90% (95% CI: 55.5–99.8%) of cases. Meanwhile, in secondary SFN, positive IVCM results detected evidence of peripheral neurodegeneration in an additional 27.3% (95% CI: 6–61%) with negative skin biopsy. Conclusion: CNFL reduction in corneal IVCM demonstrated significant diagnostic value for SFN. Since skin biopsy findings do not always correspond with IVCM findings, corneal IVCM could be applied as a complementary tool to standard skin biopsy rather than as a replacement. It might be additionally useful for detecting patchy pattern presentations of SFN, excluding neuropathy in idiopathic SFN, and detecting neuropathy in biopsy-negative secondary SFN. In patients with positive IVCM, it could also be used as a primary tool for follow-up monitoring. Full article

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

14 pages, 1694 KB

Open AccessArticle

The Impacts of Enlarged Subarachnoid Space on Brain Growth and Cortex Maturation in Very Preterm Infants

by Liangbing Wang, Yubo Zhuo, Fang Lin, Xueqing Wan, Guohui Yang and Jianlong He

Diagnostics 2025, 15(17), 2206; https://doi.org/10.3390/diagnostics15172206 (registering DOI) - 30 Aug 2025

Abstract

Objectives: The aim of this study is to investigate the changes in quantitative indices of brain volume and cortex development in preterm infants with enlarged subarachnoid space (ESS). Methods: A single-center retrospective cohort study was performed in Hong Kong University–Shenzhen Hospital from November [...] Read more.

Objectives: The aim of this study is to investigate the changes in quantitative indices of brain volume and cortex development in preterm infants with enlarged subarachnoid space (ESS). Methods: A single-center retrospective cohort study was performed in Hong Kong University–Shenzhen Hospital from November 2014 to November 2023, involving 200 preterm infants whose brain MRI images were available. Parameters including the volume of cerebrospinal fluid (CSF), brain tissues, total intracranial cavity (ICC), and key indices of cortex maturation (surface area, cortical thickness, cortical volume, mean curvature) were compared between the groups with ESS and without ESS. The retrospective nature of this study may introduce selection bias in the process of enrolling preterm infants with ESS. Results: The groups with severe and mild ESS had a significantly greater ICC volume than the group without ESS (severe: 384.66 ± 30.33 [p < 0.001]; mild: 374.25 ± 26.45 [p < 0.001] vs. no ESS: 356.78 ± 26.03), and the difference was mostly due to the gap in extra-CSF volume among the three groups (severe: 74.20 ± 5.1 and mild: 55.36 ± 3.8 vs. no ESS: 40.54 ± 4.3, p ≤ 0.001). Only the volume of parenchyma of the severe-ESS group was significantly different (severe: 302.35 ± 26.43 vs. no ESS: 312.27 ± 20.75, p = 0.003). Regarding indices of cortex maturation, only the mean curvature showed a significant difference between the three groups, and most of the significant clusters were located around the parietal and temporal lobes. Conclusions: ESS may be associated with impaired early brain maturation in preterm infants after birth. A further neurodevelopmental follow-up study is needed. Full article

(This article belongs to the Special Issue Insights into Perinatal Medicine and Fetal Medicine—2nd Edition)

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18 pages, 2338 KB

Open AccessArticle

Patients’ Experiences of Diagnostic and Therapeutic High-Resolution Endoscopy in Treating Anal Squamous Intraepithelial Lesions: A Qualitative Study

by Peter Borch-Johnsen, Hanna Dubois, Peter T. Schmidt, Jonas Nygren and Gail Dunberger

Diagnostics 2025, 15(17), 2205; https://doi.org/10.3390/diagnostics15172205 (registering DOI) - 30 Aug 2025

Abstract

Background: Anal squamous cell carcinoma is a rare disease strongly associated with the human papillomavirus (HPV) and preceded by the premalignant anal squamous intraepithelial lesion (ASIL). High-resolution anoscopy (HRA) using a colposcope is considered the gold standard for detecting and managing ASIL. Despite [...] Read more.

Background: Anal squamous cell carcinoma is a rare disease strongly associated with the human papillomavirus (HPV) and preceded by the premalignant anal squamous intraepithelial lesion (ASIL). High-resolution anoscopy (HRA) using a colposcope is considered the gold standard for detecting and managing ASIL. Despite being recommended in current guidelines for anal cancer screening, HRA availability remains limited. Although generally well tolerated, concerns about follow-up adherence persist. We have developed an endoscopic technique using high-resolution flexible endoscopes for detection, resection, and screening of ASIL. Our previous research suggests that this method is effective and gentle, but patients’ experiences of this approach remain underexplored. The aim of this study was to explore patients’ experiences of endoscopic detection, treatment, and screening of anal squamous intraepithelial lesions. Method: A qualitative approach was used involving semi-structured interviews and abductive qualitative content analysis. The 32-item COREQ checklist guided the reporting of the study. All participants followed a standardized protocol for treatment and follow-up. Results: Analysis of 16 interviews (female n = 7, male n = 9, age 19–72 years) yielded four categories: a comforting encounter in an exposed situation (with four subcategories); impact on intimate relationships (with one subcategory); living with uncertainty (with four subcategories); and physical discomfort (with two subcategories). Conclusions: High-resolution endoscopy is a well-tolerated and effective diagnostic and therapeutic modality for ASIL. However, the psychological impact of HPV-related conditions highlights the need for appropriate psychosocial support. These findings underscore the importance of integrating patient-centered care principles into the implementation of novel diagnostic and therapeutic technologies. Full article

(This article belongs to the Special Issue New Insights into Gastrointestinal Endoscopy)

14 pages, 539 KB

Open AccessArticle

Enhancing Clinician Trust in AI Diagnostics: A Dynamic Framework for Confidence Calibration and Transparency

by Yunguo Yu, Cesar A. Gomez-Cabello, Syed Ali Haider, Ariana Genovese, Srinivasagam Prabha, Maissa Trabilsy, Bernardo G. Collaco, Nadia G. Wood, Sanjay Bagaria, Cui Tao and Antonio J. Forte

Diagnostics 2025, 15(17), 2204; https://doi.org/10.3390/diagnostics15172204 (registering DOI) - 30 Aug 2025

Abstract

Background: Artificial Intelligence (AI)-driven Decision Support Systems (DSSs) promise improvements in diagnostic accuracy and clinical workflow efficiency, but their adoption is hindered by inadequate confidence calibration, limited transparency, and poor alignment with real-world decision processes, which limit clinician trust and lead to high [...] Read more.

Background: Artificial Intelligence (AI)-driven Decision Support Systems (DSSs) promise improvements in diagnostic accuracy and clinical workflow efficiency, but their adoption is hindered by inadequate confidence calibration, limited transparency, and poor alignment with real-world decision processes, which limit clinician trust and lead to high override rates. Methods: We developed and validated a dynamic scoring framework to enhance trust in AI-generated diagnoses by integrating AI confidence scores, semantic similarity measures, and transparency weighting into the override decision process using 6689 cardiovascular cases from the MIMIC-III dataset. Override thresholds were calibrated and validated across varying transparency and confidence levels, with override rate as the primary acceptance measure. Results: The implementation of this framework reduced the override rate to 33.29%, with high-confidence predictions (90–99%) overridden at a rate of only 1.7%, and low-confidence predictions (70–79%) at a rate of 99.3%. Minimal transparency diagnoses had a 73.9% override rate compared to 49.3% for moderate transparency. Statistical analyses confirmed significant associations between confidence, transparency, and override rates (p < 0.001). Conclusions: These findings suggest that enhanced transparency and confidence calibration can substantially reduce override rates and promote clinician acceptance of AI diagnostics. Future work should focus on clinical validation to optimize patient safety, diagnostic accuracy, and efficiency. Full article

(This article belongs to the Special Issue The Future of Diagnostics: Exploring the Role of Artificial Intelligence in Medicine)

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18 pages, 865 KB

Open AccessSystematic Review

Diagnostic Imaging and Clinical Implications of Heterotopic Ossification After Total Ankle Arthroplasty: A Systematic Review for Surgical Strategy

by Simone Ottavio Zielli, Francesca Veronesi, Giulia Sacchi, Antonio Mazzotti, Cesare Faldini and Gianluca Giavaresi

Diagnostics 2025, 15(17), 2203; https://doi.org/10.3390/diagnostics15172203 - 29 Aug 2025

Abstract

Background: Heterotopic ossification (HO) is a frequent radiographic finding after total ankle arthroplasty (TAA), but its clinical relevance, diagnostic criteria, and prognostic implications remain uncertain. This systematic review summarizes current evidence on HO incidence, distribution, severity, risk factors, clinical impact, and diagnostic/prognostic [...] Read more.

Background: Heterotopic ossification (HO) is a frequent radiographic finding after total ankle arthroplasty (TAA), but its clinical relevance, diagnostic criteria, and prognostic implications remain uncertain. This systematic review summarizes current evidence on HO incidence, distribution, severity, risk factors, clinical impact, and diagnostic/prognostic value to inform surgical decision-making regarding approach, implant design, and revision strategies. Methods: A systematic review was conducted according to PRISMA guidelines using PubMed, Web of Science, and Scopus databases and the following search string “heterotopic ossification” AND “ankle” (February 2015–February 2025). Twenty-two studies were included, most of which were retrospective and varied in methodological quality. Data were extracted on HO incidence, severity, clinical relevance, and factors associated with diagnosis and management. Results: HO incidence varied widely across studies. No significant associations were found between HO and surgical variables such as approach (all studies used the anterior approach) or coronal alignment. HO presence did not consistently correlate with reduced postoperative range of motion and radiographic follow-up duration. Implant design appeared to influence anatomical distribution in some comparative studies, though without statistical significance. Reoperations specifically for HO excision were rare and mainly performed for mechanical complications (impingement or osteolysis) rather than HO severity itself. Conclusions: Although HO is a frequent finding after TAA, its clinical impact appears limited and largely unpredictable. Diagnostic tools are currently limited to conventional radiography, and no reliable prognostic markers exist. Further high-quality studies are needed to define standardized diagnostic criteria and clarify the prognostic role of HO in long-term outcomes. Full article

(This article belongs to the Special Issue Novel Technologies in Orthopedic Surgery: Diagnosis and Management)

12 pages, 559 KB

Open AccessArticle

Real-Time Predictors of Return of Spontaneous Circulation in an Emergency Setting: A Five-Year Retrospective Study

by Burcu Bayramoglu, Ismail Kaftanci, Ismail Tayfur, Ramazan Guven, Sinem Guzel Ozturk, Betul Kaplan Zamanov and Berna Atli Dasdelen

Diagnostics 2025, 15(17), 2202; https://doi.org/10.3390/diagnostics15172202 - 29 Aug 2025

Abstract

Background: Cardiopulmonary resuscitation (CPR) is a highly effort-intensive intervention and, in cases of cardiac arrest, the ability to predict a return of spontaneous circulation (ROSC) is of great importance for the efficient use of resources. This real-time assessment approach offers a practical advantage [...] Read more.

Background: Cardiopulmonary resuscitation (CPR) is a highly effort-intensive intervention and, in cases of cardiac arrest, the ability to predict a return of spontaneous circulation (ROSC) is of great importance for the efficient use of resources. This real-time assessment approach offers a practical advantage by increasing the applicability of prognostic models during acute resuscitation in an emergency department. Method: In this study, the data of patients who underwent CPR in the emergency department of a tertiary care hospital between 1 June 2019 and 1 June 2024 and underwent cardiopulmonary resuscitation were retrospectively analyzed. The patients’ demographics, comorbidities, CPR characteristics, and laboratory findings were evaluated using logistic regression and ROC curve analysis to identify the predictors of ROSC. Result: Our study revealed that cases with shockable rhythms and a shorter CPR duration were more likely to achieve ROSC. Elevated levels of albumin, creatine kinase, glucose, hemoglobin, and white blood cells were significantly associated with ROSC, while higher levels of creatinine, base excess, and eosinophils were more common in non-survivors. Atrial fibrillation and neurodegenerative disease were associated with lower ROSC rates. Conclusions: Although the criteria for the termination of cardiac arrest resuscitation are not definitive, certain patient characteristics and laboratory findings may guide the prediction of ROSC or the identification of cases requiring prolonged CPR. The integration of these real-time predictors into clinical algorithms may support decision making in crowded emergency departments. Full article

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

13 pages, 806 KB

Open AccessArticle

Is Mandibular Cortical Bone and Trabecular Microarchitecture Altered by Masseter Botox Treatment? A Quantitative Perspective

by Ibrahim Burak Yuksel, Fatma Altiparmak, Serkan Bahrilli, Fatma Ucan Yarkac, Dilek Ozkan Sen and Kaan Orhan

Diagnostics 2025, 15(17), 2201; https://doi.org/10.3390/diagnostics15172201 - 29 Aug 2025

Abstract

Background/Objectives: Bruxism is a prevalent parafunctional activity that induces masticatory muscle hypertrophy and physiological mandibular bone alterations. While botulinum toxin type A (BTX-A) injections effectively reduce muscle hyperactivity, objective radiological assessment of their skeletal effects remains limited. This study aimed to quantitatively evaluate [...] Read more.

Background/Objectives: Bruxism is a prevalent parafunctional activity that induces masticatory muscle hypertrophy and physiological mandibular bone alterations. While botulinum toxin type A (BTX-A) injections effectively reduce muscle hyperactivity, objective radiological assessment of their skeletal effects remains limited. This study aimed to quantitatively evaluate the impact of BTX-A on mandibular trabecular bone structure by assessing potential reductions in fractal dimension (FD) in bruxism patients compared to controls. Methods: This retrospective matched-pair study included 42 bruxism patients (39 females, 3 males) receiving 50 U of BTX-A in masseter muscles and 32 age-matched non-bruxism controls (30 females, 2 males). Pre- and 6-month post-treatment panoramic radiographs were analyzed. FD values were calculated from bilateral condylar neck, ramus, and angulus regions. Results: Statistically significant reductions in FD values were observed in the angulus regions post-treatment (Right: 1.3856 to 1.2995; Left: 1.3718 to 1.2529, p < 0.001). Postoperative FD values in the BTX-A group showed no significant differences when compared to the control group (p > 0.05). Conclusions: BTX-A administration leads to measurable, region-specific reductions in mandibular trabecular bone fractal dimension, particularly in the angulus. The postoperative similarity to the control group suggests a potential normalization of bone structure following treatment. These findings highlight the clinical utility of fractal analysis for monitoring osseous adaptations in neuromuscular interventions. Full article

(This article belongs to the Special Issue Advances in Oral and Maxillofacial Imaging)

17 pages, 1316 KB

Open AccessArticle

Clinical and Virological Profiles Associated with CINTEC^® PLUS Positivity: A Data-Driven Clustering and Modeling Study

by Iulian-Valentin Munteanu, Demetra Socolov, Razvan Socolov, Ana-Maria Adam, Gigi Adam, Ingrid-Andrada Vasilache, Petronela Vicoveanu, Valeriu Harabor, Anamaria Harabor and Alina-Mihaela Calin

Diagnostics 2025, 15(17), 2200; https://doi.org/10.3390/diagnostics15172200 - 29 Aug 2025

Abstract

Background/Objectives: The diagnostic performance of CINtec^® PLUS can be influenced by numerous patient characteristics and risk factors. The aim of this retrospective study was to evaluate and model the risk factors associated with CINtec^® PLUS test positivity in patients undergoing [...] Read more.

Background/Objectives: The diagnostic performance of CINtec^® PLUS can be influenced by numerous patient characteristics and risk factors. The aim of this retrospective study was to evaluate and model the risk factors associated with CINtec^® PLUS test positivity in patients undergoing cervical cancer screening and to assess their predictive performance for the prediction of cervical intraepithelial neoplasia (CIN) 2/3 using an unsupervised machine learning-based model. Methods: Medical data of 134 patients with human papillomavirus (HPV) infection who underwent CINtec^® PLUS testing were used to model the impact of risk factors on dual-stain cytology positivity and to evaluate the predictive performance for CIN2/3. Results: The gradient boosting classifier for the prediction of CINtec^® PLUS positivity using clinical risk factors had a precision of 75%, an overall accuracy of 0.62, and an area under the curve (AUC) value of 0.77. Body mass index and age were the most important variables in this model. HSIL, ASC-US, and other high-risk HPV strains increased the likelihood of a positive outcome. Overall AUC values for a positive test alone were 0.74 and 0.69 for CIN2 and CIN3 prediction, respectively. For CIN2 prediction, the XGBoost model performed well, with 71% sensitivity, 85% specificity, and an AUC value of 0.90. However, the model had 96% sensitivity, 25% specificity, and 0.58 AUC for CIN3 prediction. Conclusions: Patient characteristics and risk factors can influence CINtec^® PLUS positivity rates and they need to be carefully considered before choosing a specific management. Full article

(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers: Third Edition)

13 pages, 1389 KB

Open AccessArticle

Sella Turcica and Cranial Base Symmetry in Anterior Synostotic Plagiocephaly Patients: A Retrospective Case–Control Study

by Edoardo Staderini, Davide Guerrieri, Michele Tepedino, Gianmarco Saponaro, Alessandro Moro, Giulio Gasparini, Patrizia Gallenzi and Massimo Cordaro

Diagnostics 2025, 15(17), 2199; https://doi.org/10.3390/diagnostics15172199 - 29 Aug 2025

Abstract

Background/Objectives: The present case–control study aims to compare the symmetry of the sella turcica and cranial base of nine patients with anterior unicoronal synostotic plagiocephaly (ASP) and nine healthy patients referred to the maxillofacial unit of the Fondazione Policlinico Universitario Agostino Gemelli. [...] Read more.

Background/Objectives: The present case–control study aims to compare the symmetry of the sella turcica and cranial base of nine patients with anterior unicoronal synostotic plagiocephaly (ASP) and nine healthy patients referred to the maxillofacial unit of the Fondazione Policlinico Universitario Agostino Gemelli. The primary aim of this study is to assess changes in the morphology of the sella turcica and skull base in comparison with a healthy control population using both a 2D and 3D analysis of the sella turcica and skull base. Methods: Computed tomography (CT) scans of nine ASP patients from the Fondazione Policlinico Universitario Agostino Gemelli in Rome were retrieved. A quantitative evaluation of the skull base and the sella turcica was performed through the asymmetry index (A.I.), obtained from the comparison of the point-to-point distances ipsilateral and contralateral to the synostosis. A qualitative three-dimensional (3D) evaluation of the asymmetry of the sella turcica was performed by comparing each sella model with its mirrored counterpart; then, the root mean square (RMS) displacement between the original and mirrored 3D models was calculated. Results: The results showed higher A.I. values in the study group, particularly the length of the anterior cranial fossa, with A.I. values of 7.96 (study) vs. 0.02 (control). Conclusions: The higher values of the asymmetry index observed in the study group supported the presence of statistically significant asymmetries in the sella and cranial fossa measurements compared to the control group. Full article

(This article belongs to the Special Issue Advancements in Craniofacial Practices: Imaging, AI, Surgery, and Patient Care)

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11 pages, 2820 KB

Open AccessCase Report

An Enhanced Method for Left Bundle Branch Area Pacing Lead Extraction Using Continuous Femoral Pigtail Countertraction

by Andrei Mihnea Rosu, Theodor Georgian Badea, Florentina Luminita Tomescu, Emanuel Stefan Radu, Maria-Daniela Tanasescu, Eduard George Cismas and Oana Andreea Popa

Diagnostics 2025, 15(17), 2198; https://doi.org/10.3390/diagnostics15172198 - 29 Aug 2025

Abstract

Background: Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative to conventional pacing, offering improved ventricular synchrony and clinical outcomes. However, extraction of deeply implanted LBBAP leads remains challenging, particularly in the context of device-related infections. Case Summary: We [...] Read more.

Background: Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative to conventional pacing, offering improved ventricular synchrony and clinical outcomes. However, extraction of deeply implanted LBBAP leads remains challenging, particularly in the context of device-related infections. Case Summary: We report two cases of successful extraction of chronically implanted LBBAP leads using a novel technique based on femoral countertraction with pigtail catheters. In the first case, a deep septal implanted 3830 lead was extracted in a patient with persistent bacteremia and suspected device-related endocarditis. Continuous traction was applied to the mid-portion of the lead using a pigtail catheter introduced via femoral access, facilitating safe removal without the use of powered sheaths proximal to the distal tip of the lead. In the second case, three leads (RA, RV, LBBAP) from a cardiac resynchronization therapy with deffibrilation support (CRT-D) system were completely removed in a patient with device extrusion and pocket erosion, using a dual pigtail approach anchored to the atrial and septal leads. Results: In both cases, the technique enabled successful extraction without complications. Procedural times were approximately 70 and 65 min, respectively. In vitro testing suggested that the pigtail catheter applied a sustained moderate traction force (~0.06 kgf), translating to an estimated pressure of 0.85–1.91 kgf/cm² at the septal lead interface. Conclusions: This case series demonstrates that LBBAP lead extraction is feasible using a novel femoral countertraction technique with pigtail catheters. Steady, moderate traction over time may provide a safer alternative to forceful subclavicular extraction, especially in chronically implanted deep septal leads. Further studies are warranted to evaluate the reproducibility, safety, and clinical applicability of this approach. Full article

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

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33 pages, 473 KB

Open AccessReview

Transforming Breast Imaging: A Narrative Review of Systematic Evidence on Artificial Intelligence in Mammographic Practice

by Andrea Lastrucci, Nicola Iosca, Yannick Wandael, Angelo Barra, Renzo Ricci, Jacopo Nori Cucchiari, Nevio Forini, Graziano Lepri and Daniele Giansanti

Diagnostics 2025, 15(17), 2197; https://doi.org/10.3390/diagnostics15172197 - 29 Aug 2025

Abstract

Background: Breast cancer is still the most common type of cancer worldwide. Advances and the global use of artificial intelligence (AI) have opened up new opportunities to improve diagnostic accuracy and optimize breast cancer screening. This review summarizes the findings from systematic [...] Read more.

Background: Breast cancer is still the most common type of cancer worldwide. Advances and the global use of artificial intelligence (AI) have opened up new opportunities to improve diagnostic accuracy and optimize breast cancer screening. This review summarizes the findings from systematic reviews to assess the current situation of AI integration in mammography. Methods: A total of 28 systematic reviews were included and analyzed using a standardized narrative checklist to assess the impact of AI on mammography imaging. Bibliometric analysis and thematic synthesis were used to assess trends, evaluate the performance of AI in different modalities and identify challenges and opportunities for clinical implementation. Results and Discussion: AI technologies show an overall performance comparable to radiologists in terms of sensitivity and specificity, especially when integrated with human interpretation to detect breast cancer in mammography. However, most studies are retrospective, which raises concerns about their generalizability to real-world clinical settings. Key limitations include potential dataset bias—often stemming from the over-representation of specific imaging equipment or clinical environments—limited ethnic and demographic diversity, the lack of model explainability that hinders clinical trust, and an unclear or evolving legal and regulatory framework that complicates integration into standard practice. Conclusions: AI has the potential to transform mammography screening, but its integration into the real world requires prospective validation, ethical safeguards and robust regulatory oversight. Coordinated international efforts are essential to ensure that AI is used safely, fairly and effectively in breast cancer diagnostics. Full article

(This article belongs to the Special Issue Artificial Intelligence for Health and Medicine)

18 pages, 2661 KB

Open AccessReview

Current Trends and Future Directions of Digital Pathology and Artificial Intelligence in Dermatopathology: A Scientometric-Based Review

by Iuliu Gabriel Cocuz, Raluca Niculescu, Maria-Cătălina Popelea, Maria Elena Cocuz, Adrian-Horațiu Sabău, Andreea-Cătălina Tinca, Andreea Raluca Cozac-Szoke, Diana Maria Chiorean, Corina Eugenia Budin and Ovidiu Simion Cotoi

Diagnostics 2025, 15(17), 2196; https://doi.org/10.3390/diagnostics15172196 - 29 Aug 2025

Abstract

Background: Digital Pathology (DP) and Artificial Intelligence (AI) have strongly developed in recent years, especially in pathology, with a high interest in dermatopathology. Accelerated by the COVID-19 pandemic, DP and AI are now integrated in pathology, research and education, bringing value to histopathological [...] Read more.

Background: Digital Pathology (DP) and Artificial Intelligence (AI) have strongly developed in recent years, especially in pathology, with a high interest in dermatopathology. Accelerated by the COVID-19 pandemic, DP and AI are now integrated in pathology, research and education, bringing value to histopathological diagnoses, telepathology and personalized medicine. This narrative review presents a comprehensive literature review by defining three research directions, using scientometric analysis, of the current state of DP and AI in pathology and dermatopathology. Methods: The research was conducted through the Pubmed and Web of Science databases, within the research period of January 2019–July 2025: a two-phase methodology. Four independent pathologists selected the articles in accordance with the inclusion and exclusion criteria, and the synthesis of the articles was based on three research directions. Results: The research shows that CNN (Convolutional Neural Network), AI powered diagnostic platforms and telepathology strongly contribute to increasing the speed and accuracy of diagnostics, especially on cutaneous malignant skin tumors. There are still several challenges and limitations in terms of validation, interoperability, initial high implementation costs, ethics and transparency in AI and equity in healthcare. Conclusions: DP and AI are essential pillars of modern dermatopathology, with a high necessity of standardization, regulation and a multidisciplinary approach. Full article

(This article belongs to the Special Issue Latest News in Digital Pathology)

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7 pages, 682 KB

Open AccessInteresting Images

Palatal Abscess of Endodontic Origin with Extensive Radiolucency in Maxillary CBCT Imaging

by Diana Marian, George Dumitru Constantin, Ademir Horia Stana, Ioana Elena Lile, Tareq Hajaj and Otilia Lavinia Gag (Stana)

Diagnostics 2025, 15(17), 2195; https://doi.org/10.3390/diagnostics15172195 - 29 Aug 2025

Abstract

Palatal abscesses of endodontic origin are rarer than buccal ones due to maxillary anatomy. Their clinical appearance may resemble that of other palatal illnesses, complicating diagnosis and treatment. Prevention of problems requires early detection and endodontic treatment. A 26-year-old female patient presented with [...] Read more.

Palatal abscesses of endodontic origin are rarer than buccal ones due to maxillary anatomy. Their clinical appearance may resemble that of other palatal illnesses, complicating diagnosis and treatment. Prevention of problems requires early detection and endodontic treatment. A 26-year-old female patient presented with a 2 cm diameter palatal abscess, significant pulsatile discomfort, fever, and enlargement of the anterior hard palate. Clinical examination showed grade 1 mobility of the central and lateral incisors, percussion discomfort, and negative pulp vitality in the case of the lateral incisor. Cone-beam computed tomography (CBCT) showed two radiolucent lesions: a posterior cystic lesion near the first molar and an anterior lesion near the upper left lateral incisor. Palatal cortical bone puncture and soft tissue extension indicated the abscess origin. According to the clinical and imaging evaluation, the upper left lateral incisor had a persistent periapical lesion of endodontic origin that a palatal abscess with cortical bone perforation had exacerbated. Full article

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

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15 pages, 1052 KB

Open AccessSystematic Review

Continuous Wearable-Sensor Monitoring After Colorectal Surgery: A Systematic Review of Clinical Outcomes and Predictive Analytics

by Calin Muntean, Vasile Gaborean, Alaviana Monique Faur, Ionut Flaviu Faur, Cătălin Prodan-Bărbulescu and Catalin Vladut Ionut Feier

Diagnostics 2025, 15(17), 2194; https://doi.org/10.3390/diagnostics15172194 - 29 Aug 2025

Abstract

Background and Objectives: Early ambulation and timely detection of postoperative complications are cornerstones of colorectal Enhanced Recovery After Surgery (ERAS) programmes, yet the traditional bedside checks performed every 4–8 h may miss clinically relevant deterioration. The consumer wearables boom has spawned a new [...] Read more.

Background and Objectives: Early ambulation and timely detection of postoperative complications are cornerstones of colorectal Enhanced Recovery After Surgery (ERAS) programmes, yet the traditional bedside checks performed every 4–8 h may miss clinically relevant deterioration. The consumer wearables boom has spawned a new generation of wrist- or waistband-mounted sensors that stream step count, heart-rate and temperature data continuously, creating an opportunity for data-driven early-warning strategies. No previous systematic review has focused exclusively on colorectal surgery. Methods: Three databases (PubMed, Embase, and Scopus) were searched (inception—1 May 2025) for prospective or retrospective studies that used a consumer-grade or medical-grade wearable to collect objective physical-activity or vital-sign data during the peri-operative period of elective colorectal resection. Primary outcomes were postoperative complication rates, length-of-stay (LOS) and 30-day readmission. Two reviewers screened records, extracted data and performed risk-of-bias appraisals with ROBINS-I or RoB 2. Narrative synthesis was adopted because of the heterogeneity in devices, recording windows and outcome definitions. Results: Nine studies (n = 778 patients) met eligibility: one randomised controlled trial (RCT), seven prospective cohort studies and one retrospective analysis. Five studies relied on step-count metrics alone; four combined step-count with heart-rate or skin-temperature streams. Median wear time was 6 d (range 2–30). Higher day-1 step count (≥1000 steps) was associated with shorter LOS (odds ratio 0.63; 95% CI 0.45–0.84). Smart-band–augmented ERAS pathways shortened protocol-defined LOS by 1.1 d. Pre-operative inactivity (<5000 steps·day⁻¹) and low “return-to-baseline” activity on the day before discharge independently predicted any complication (OR 0.39) and 30-day readmission (OR 0.60 per 10% increment). A prospective 101-patient study that paired pedometer-recorded ambulation with daily lung-ultrasound scores found fewer pulmonary complications when patients walked further (Spearman r = –0.36, p < 0.05). Conclusions: Continuous, patient-worn sensors are feasible and yield clinically meaningful data after colorectal surgery. Early postoperative step-count trajectories and activity-derived recovery indices correlate with LOS, complications and readmission, supporting their incorporation into digital ERAS dashboards. Standardised outcome definitions, open algorithms for signal processing and multicentre validation are now required. Full article

(This article belongs to the Special Issue Diagnosis and Management of Colorectal Diseases)

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14 pages, 1591 KB

Open AccessReview

The Diagnosis, Management, and Outcomes of Gradenigo Syndrome in Children: A Scoping Review of the Literature

by Charles Schmit, Felix Keller, Timo Gottfried, Roland Hartl, Lea Stecher, Andrea Tröger, Matthias Santer, Veronika Innerhofer, Avneet Radhawa, Joachim Schmutzhard, Benedikt Hofauer and Annette Runge

Diagnostics 2025, 15(17), 2193; https://doi.org/10.3390/diagnostics15172193 - 29 Aug 2025

Abstract

Purpose: Gradenigo syndrome is a rare complication of acute otitis media (AOM) in children, characterized by suppurative otitis media, unilateral facial pain, and ipsilateral abducens nerve palsy. This review summarizes pediatric data on the presentation, diagnostics, treatment, and outcomes. Methods: A [...] Read more.

Purpose: Gradenigo syndrome is a rare complication of acute otitis media (AOM) in children, characterized by suppurative otitis media, unilateral facial pain, and ipsilateral abducens nerve palsy. This review summarizes pediatric data on the presentation, diagnostics, treatment, and outcomes. Methods: A literature research was conducted using the terms “Gradenigo syndrome,” “petrous apicitis,” and “complications otitis media.” Pediatric cases were analyzed for demographics, symptoms, diagnostic findings, therapeutic strategies, and clinical outcomes. Results: Sixty-three articles described 65 patients (mean age: 8.0 years). The classic triad occurred in 22% of cases; 74% showed incomplete presentations. Imaging revealed petrous apex inflammation (84%) and petrous bone tip obliteration (49%). Antibiotics were administered in 88% of cases, most commonly third-generation cephalosporins. Surgery was performed in 72%, mainly myringotomy, tympanostomy tube insertion, and mastoidectomy; no direct petrous apex approaches were reported. Pathogens were identified in 41% of cases, most commonly Fusobacterium necrophorum. Clinical improvement occurred in 98%, with 75% achieving a complete resolution; complications were reported in 29%, including one fatality (2%). Conclusions: Given its variable presentation, comprehensive diagnostic imaging is essential for the diagnosis of Gradenigo syndrome. Early broad-spectrum antibiotic therapy is essential. Surgical intervention is required in severe cases. Long-term targeted antibiotic therapy may help prevent recurrence. Full article

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

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26 pages, 1617 KB

Open AccessSystematic Review

Uterine Artery Pulsatility Index in Singleton Pregnancies Conceived via Assisted Reproductive Technology Versus Spontaneous Conception: A Systematic Review and Meta-Analysis

by Antonios Siargkas, Ioannis Tsakiridis, Areti Faka, Dimitra Kappou, Ioannis Papastefanou and Themistoklis Dagklis

Diagnostics 2025, 15(17), 2192; https://doi.org/10.3390/diagnostics15172192 - 29 Aug 2025

Abstract

Background/Objectives: Uterine artery pulsatility index (UtA-PI) is a key biomarker of placental function, but its clinical interpretation in assisted reproductive technology (ART) pregnancies is uncertain. This meta-analysis aimed to assess trimester- and method-specific UtA-PI differences between ART and spontaneous conceptions (SC) and to [...] Read more.

Background/Objectives: Uterine artery pulsatility index (UtA-PI) is a key biomarker of placental function, but its clinical interpretation in assisted reproductive technology (ART) pregnancies is uncertain. This meta-analysis aimed to assess trimester- and method-specific UtA-PI differences between ART and spontaneous conceptions (SC) and to examine associated risks for preeclampsia (PE) and small-for-gestational-age (SGA) neonates to contextualize its findings. Methods: A systematic search of MEDLINE, Scopus, and the Cochrane Library was conducted through 25 June 2025. We included observational studies comparing UtA-PI and perinatal outcomes in singleton ART versus SC pregnancies. The primary outcome was the standardized mean difference (SMD) in first (until the 13⁺⁶ gestational week) and second trimester (14⁺⁰–23⁺⁶ gestational weeks) UtA-PI measurements; secondary outcomes were PE and SGA rates. Analyses were stratified by ART modalities. Random-effects models were used, and study quality was evaluated using the Newcastle–Ottawa Scale and risk of bias with QUIPS tool (INPLASY registration: INPLASY202560104). Results: Thirteen cohort studies were included. Overall, ART pregnancies had significantly lower UtA-PI values than SC in both the first (SMD = −0.28; 95% CI: −0.53 to −0.03) and second trimesters (SMD = −0.20; 95% CI: −0.36 to −0.04). These reductions were driven by oocyte donation (first-trimester SMD = −0.70; 95% CI: −1.21 to −0.18; second-trimester SMD = −0.46; 95% CI: −0.65 to −0.26) and artificial cycle frozen embryo transfers (ET) (first-trimester SMD = −0.69; 95% CI: −1.00 to −0.39). These lower UtA-PI values typically suggest better placental perfusion and a lower risk of placental related complications. However, ART pregnancies had an elevated overall risk for PE (risk ratio [RR] = 2.32; 95% CI: 1.72 to 3.12), with the highest risk in oocyte donation (RR = 6.11; 95% CI: 3.35 to 11.17) and artificial cycle frozen ET (RR = 3.45; 95% CI: 1.51 to 7.90). Conclusions: ART pregnancies, particularly from oocyte donation and artificial cycle frozen ET, show lower UtA-PI values despite a significantly elevated risk for PE. This finding suggests that mechanisms other than placental perfusion contribute to PE development. Clinically, the ART method is an independent risk factor for PE, and UtA-PI interpretation should be adjusted accordingly. Further research is crucial to elucidate the underlying pathophysiology. Full article

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

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