Diagnostics

32 pages, 1961 KB

Open AccessReview

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

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

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

Abstract

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

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

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

12 pages, 1079 KB

Open AccessArticle

Enhanced Prediction of Cardiovascular Disease Through Integrated Machine Learning Models Combining Clinical and Demographic Characteristics

by Zhe Zhang, Dengao Li, Jumin Zhao, Huiting Ma, Fei Wang and Qinglian Hao

Diagnostics 2026, 16(10), 1572; https://doi.org/10.3390/diagnostics16101572 - 21 May 2026

Abstract

Background/Objectives: Heart failure (HF) remains a major cause of global mortality and morbidity; it is, therefore, of paramount importance that diagnosis and prognostication are made timely in order to better improve outcomes and reduce healthcare expenditure. This research presents a novel predictive model [...] Read more.

Background/Objectives: Heart failure (HF) remains a major cause of global mortality and morbidity; it is, therefore, of paramount importance that diagnosis and prognostication are made timely in order to better improve outcomes and reduce healthcare expenditure. This research presents a novel predictive model of heart failure that combines clinical criteria with demographic factors in order to maximize predictive performance and act as a reliable tool for individualized healthcare intervention. Methods: Complex machine learning techniques, including decision trees, random forest, and deep learning, are applied in analyzing a large dataset of subjects with heart failure. We collected a diverse dataset comprising clinical indicators such as echocardiographic data, biomarkers, electrocardiogram (ECG) features, and demographic information. Data preprocessing techniques, such as feature normalization and handling of missing values, were applied to ensure the integrity and reliability of the dataset. Results: The results indicate that integrating both clinical indicators and demographic characteristics significantly improves the predictive power of the model, compared to models based on clinical indicators alone. Specifically, the hybrid model demonstrated a superior ability to predict short- and long-term outcomes in heart failure patients, offering enhanced accuracy in risk stratification and prognosis prediction. Conclusions: This research highlights the potential of artificial intelligence (AI) and machine learning in revolutionizing heart failure care by providing healthcare professionals with more accurate, data-driven decision support tools. The proposed model not only holds promise for clinical applications but also offers insights for future research into personalized medicine. Full article

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

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22 pages, 575 KB

Open AccessReview

Ultrasound and Shear Wave Elastography of Lower-Limb Muscles and Aponeurotic Structures in Human Cadavers—A Scoping Review

by Filippo Tilli, Giorgio Tamborrini and Felix Margenfeld

Diagnostics 2026, 16(10), 1571; https://doi.org/10.3390/diagnostics16101571 - 21 May 2026

Abstract

Background: Human cadaveric models provide a controlled experimental setting to investigate the anatomical basis and mechanical behaviour underlying musculoskeletal ultrasound findings. In recent years, both B-mode ultrasound and shear wave elastography have been applied in cadaveric studies to explore muscle architecture, aponeurotic [...] Read more.

Background: Human cadaveric models provide a controlled experimental setting to investigate the anatomical basis and mechanical behaviour underlying musculoskeletal ultrasound findings. In recent years, both B-mode ultrasound and shear wave elastography have been applied in cadaveric studies to explore muscle architecture, aponeurotic structures, and passive mechanical properties under standardized conditions. Objective: The aim of this scoping review was to map and synthesize cadaveric studies using ultrasound and shear wave elastography to investigate lower-limb muscles and their aponeurotic structures, with emphasis on methodological applications, anatomical insights, and limitations relevant to clinical interpretation. Material and Methods: A scoping review was conducted according to PRISMA-ScR principles. Studies were included if ultrasound imaging (B-mode and/or shear wave elastography) was applied directly to human cadaveric lower-limb muscles or aponeurotic structures. Data were extracted and synthesized descriptively by anatomical region and ultrasound technique. Results: A total of 11 studies met the inclusion criteria and were included in the final qualitative synthesis, all of which applied ultrasound imaging, with or without shear wave elastography, directly to human cadaveric muscle tissue Among these, seven studies specifically investigated lower-limb skeletal muscles and their aponeurotic structures using ultrasound-based techniques to describe muscle architecture, internal connective tissue anatomy, or passive mechanical behaviour. These studies focused on the quadriceps femoris, hamstrings, adductor longus, and the gastrocnemius–soleus complex. The remaining four studies were considered relevant and therefore included in the scoping review because, although they did not focus on a specific lower-limb muscle group, they addressed key methodological factors influencing ultrasound and elastography-derived measurements in cadaveric muscle tissue. These investigations examined the effects of tissue layering, specimen-related characteristics, and measurement conditions, thereby providing essential methodological context for the interpretation of ultrasound-based outcomes across different anatomical regions. Conclusions: Cadaveric ultrasound studies provide essential anatomical context for interpreting musculoskeletal ultrasound, while cadaveric shear wave elastography supports controlled exploration of passive muscle mechanics. At the same time, these studies highlight important methodological sensitivities that should be acknowledged before translating elastography findings to clinical decision-making. Full article

(This article belongs to the Special Issue Advances in Elastography for Applications in Rehabilitation, Physiotherapy, and Sports Sciences)

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20 pages, 2190 KB

Open AccessArticle

Comparative Evaluation of Feature Extractors, Aggregation Strategies, and Classification Hierarchies for Ovarian Cancer Subtype Classification in Whole Slide Images

by Ho Jung Song, You Sang Cho and Yong Suk Kim

Diagnostics 2026, 16(10), 1570; https://doi.org/10.3390/diagnostics16101570 - 21 May 2026

Abstract

Background/Objectives: Multiple instance learning (MIL) is widely used for automated classification of epithelial ovarian cancer subtypes from whole slide images (WSIs), but the relative contributions of feature extractor, aggregation strategy, and classification framework (flat vs. hierarchical) choices remain unclear under severe class [...] Read more.

Background/Objectives: Multiple instance learning (MIL) is widely used for automated classification of epithelial ovarian cancer subtypes from whole slide images (WSIs), but the relative contributions of feature extractor, aggregation strategy, and classification framework (flat vs. hierarchical) choices remain unclear under severe class imbalance. Methods: We evaluated 36 configurations on 510 WSIs from the UBC-OCEAN dataset using stratified five-fold cross-validation, comparing three pathology foundation models (Phikon-v2, CTransPath, UNI), six aggregators (mean/max pooling, ABMIL, CLAM-SB, DSMIL, DTP-TransMIL), and two classification strategies. Pathologist-annotated WSIs assessed attention map interpretability. Results: Feature extractor selection contributed substantially more variance than aggregator choice. Cascade balanced accuracy ranged from 0.538 (Phikon-v2) to 0.925 (UNI); CTransPath (~32 K pretraining WSIs) reached 0.870, exceeding Phikon-v2 (~58 K WSIs) and approaching UNI (~100 K+ WSIs), indicating that pretraining objective and architecture contribute as substantially as scale. The hierarchical cascade consistently improved high-grade serous carcinoma (HGSC) recall across all six evaluated configurations (+0.073 to +0.530), detecting 206 of 217 cases (0.949) with UNI max pooling. Quantitative spatial alignment analysis confirmed that both stronger feature extractors—CTransPath and UNI—generated significantly more spatially structured attention distributions than Phikon-v2 (paired Wilcoxon, p = 0.008 and p = 0.032, respectively). Conclusions: Feature extractor choice contributed more variance than aggregator selection, with the largest gap between Phikon-v2 and stronger extractors. Hierarchical cascades consistently improved HGSC recall across all configurations. Full article

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

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16 pages, 2011 KB

Open AccessArticle

Gravitational 3D Magnetic Resonance Elastography for Differentiating Focal Nodular Hyperplasia and Hepatic Adenoma

by Leon David Gruenewald, Shayan Mansouri, Christian Booz, Jennifer Gotta, Philipp Reschke, Tommaso D’Angelo, Mohamed Alrahmoun, Scherwin Mahmoudi, Simon S. Martin, Katrin Eichler, Tatjana Gruber-Rouh, Stefan Zeuzem, Esra Görgülü, Melis Onay, Eva Herrmann, Maria Johanna Gobertina Tetuanui Vehreschild, Katharina Schregel, Sandra Ciesek, Sebastian Haberkorn, Thomas Joseph Vogl, Ralph Sinkus and Vitali Koch Show full author list Hide full author list

Diagnostics 2026, 16(10), 1569; https://doi.org/10.3390/diagnostics16101569 - 21 May 2026

Abstract

Background/Objectives: Differentiating focal nodular hyperplasia (FNH) from hepatic adenoma (HA) remains challenging, as FNH is benign whereas HA carries risks of hemorrhage and malignant transformation. This prospective single-center pilot study evaluated the diagnostic performance of three-dimensional magnetic resonance elastography (3D-MRE) using a gravitational [...] Read more.

Background/Objectives: Differentiating focal nodular hyperplasia (FNH) from hepatic adenoma (HA) remains challenging, as FNH is benign whereas HA carries risks of hemorrhage and malignant transformation. This prospective single-center pilot study evaluated the diagnostic performance of three-dimensional magnetic resonance elastography (3D-MRE) using a gravitational transducer for non-invasive differentiation of FNH and HA. Methods: Thirty-three participants (23 FNH, 10 HA) underwent 3D-MRE using the gravitational transducer. Viscoelastic parameters—stiffness, shear wave speed (Cs), wave attenuation, and phase angle—were quantified for lesions and background parenchyma.

Δ

-values were calculated by subtracting background liver measurements from lesion values. Results: FNH demonstrated significantly higher stiffness than HA (median 3.16 vs. 2.58 kPa; p = 0.02) and higher Cs (median 1.81 vs. 1.64 m/s; p = 0.001). Normalized stiffness differences (

Δ

stiffness) were significantly greater in FNH than HA (median 0.83 vs. 0.10 kPa; p = 0.001). Generalized additive models revealed divergent volume-dependent stiffening behaviors. In ROC analysis,

Δ

stiffness and

Δ

Cs each achieved an AUC of 0.87, indicating that single background-normalized viscoelastic parameters carry the principal diagnostic signal. An exploratory multivariable combination of

Δ

stiffness with patient age produced an apparent AUC of 0.93 with wide odds-ratio confidence intervals, and is presented as hypothesis-generating rather than as a clinical prediction model. Conclusions: In this pilot cohort, 3D-MRE using the gravitational transducer showed encouraging parameter-level separation between FNH and HA, with background normalization enhancing discrimination. Wave attenuation and phase angle did not differ significantly between lesion types. Given the small sample size (particularly the HA subgroup of ten patients), the mixed reference standard (histological confirmation in only 14 of 33 lesions; definitive hepatobiliary-phase MRI criteria in 19 of 33), the single-slice ROI used for lesion measurement, and the incomplete characterization of background liver parenchyma, these findings should be regarded as hypothesis-generating and require external validation in larger, multicenter cohorts before any clinical application. Full article

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

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20 pages, 4148 KB

Open AccessArticle

Intraoperative Multimodal Bowel Perfusion Quantification Combining Hyperspectral Imaging and Indocyanine Green

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

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

Abstract

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

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

(This article belongs to the Section Biomedical Optics)

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13 pages, 896 KB

Open AccessArticle

Accuracy and Agreement of a 45 mg Versus a 75 mg ¹³C-Urea Breath Test for the Diagnosis of Helicobacter pylori Infection in Adults: A Randomized Crossover Trial

by Jun Huang, Yaohong Xie, Jian Huang, Bingyun Lu and Ye Chen

Diagnostics 2026, 16(10), 1567; https://doi.org/10.3390/diagnostics16101567 - 21 May 2026

Abstract

Background: The optimal ¹³C-urea breath test (UBT) dosage for diagnosing Helicobacter pylori remains debated. We compared the accuracy and agreement of a low-dose 45 mg tablet (without citric acid) versus the standard 75 mg granule (with citric acid) protocol. Methods: In this [...] Read more.

Background: The optimal ¹³C-urea breath test (UBT) dosage for diagnosing Helicobacter pylori remains debated. We compared the accuracy and agreement of a low-dose 45 mg tablet (without citric acid) versus the standard 75 mg granule (with citric acid) protocol. Methods: In this prospective, randomized crossover trial, adults underwent both a 45 mg and a 75 mg ¹³C-UBT on the same day. Breath samples were collected at 15 and 30 min. The primary outcome was diagnostic agreement at 30 min. Secondary outcomes included diagnostic performance against a composite reference standard, wherein concordant 45 mg and 75 mg UBT results were presumed to represent true H. pylori status, while discordant cases underwent endoscopic reference testing (rapid urease test and histology, with immunohistochemistry where required), stratified by age and BMI. Results: For the 431 participants included, the 45 mg and 75 mg tests showed substantial agreement at 30 min (90.3%; κ = 0.766). The 30 min sampling time yielded significantly better accuracy than 15 min for both doses. The 45 mg protocol achieved excellent accuracy (AUC 0.953), statistically non-inferior to the 75 mg protocol (AUC 0.966; p = 0.50). Notably, in participants aged <40 years or with BMI < 25.0 kg/m², the 45 mg protocol demonstrated robust performance (AUC 0.977 and 0.966, respectively), comparable to the 75 mg standard (p > 0.05). No adverse events occurred. Conclusions: The low-dose 45 mg ¹³C-UBT provides high diagnostic agreement and comparable clinical performance to the standard 75 mg protocol without requiring citric acid acidification. Its robust performance in younger, lower-BMI individuals shows clinical promise. However, because diagnostic accuracy analyses partly relied on a composite reference assumption, further externally validated studies are required before broad screening-policy claims can be made. Full article

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

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5 pages, 4103 KB

Open AccessInteresting Images

Acute Esophageal Mucosal Lesion Mimicking Severe Reflux Esophagitis in Diabetic Ketoacidosis: A Diagnostic Pitfall

by Yohei Midori, Koji Hayashi, Maho Hayashi and Hidetaka Matsuda

Diagnostics 2026, 16(10), 1566; https://doi.org/10.3390/diagnostics16101566 - 21 May 2026

Abstract

A 65-year-old man with type 2 diabetes presented with abdominal pain. Although he had no typical reflux symptoms such as heartburn or acid regurgitation, esophagogastroduodenoscopy (EGD) showed findings suggestive of reflux esophagitis, and proton pump inhibitor therapy was initiated. Two months later, he [...] Read more.

A 65-year-old man with type 2 diabetes presented with abdominal pain. Although he had no typical reflux symptoms such as heartburn or acid regurgitation, esophagogastroduodenoscopy (EGD) showed findings suggestive of reflux esophagitis, and proton pump inhibitor therapy was initiated. Two months later, he was admitted with intractable vomiting. EGD demonstrated diffuse circumferential mucosal injury without black discoloration, predominantly in the distal esophagus. These findings were interpreted as severe reflux esophagitis (Los Angeles grade D; RE-D). Symptoms improved with supportive care, glycemic control, and continued PPI therapy; follow-up EGD showed marked improvement. Six months later, he re-presented with identical symptoms and endoscopic findings. Laboratory testing confirmed diabetic ketoacidosis (DKA), with ketonuria, elevated total ketone bodies (2469 µmol/L), and high-anion gap metabolic acidosis (anion gap 17.2 mEq/L). The diagnosis was revised to DKA-associated acute esophageal mucosal lesion (AEML). He improved with fluid resuscitation and insulin therapy, and medication adherence was reinforced. Follow-up EGD showed complete healing without recurrence. AEML has been proposed as a spectrum that includes acute esophageal necrosis (AEN; “black esophagus”) and esophagitis without black-appearing mucosa. This case highlights a diagnostic pitfall in which DKA-associated AEML without black discoloration may be misattributed to severe reflux esophagitis. When the clinical presentation or endoscopic appearance is severe or atypical, clinicians should consider AEML and evaluate for underlying systemic precipitants. Full article

(This article belongs to the Special Issue Advances in Endoscopy—A New Era in Gastrointestinal Diagnostics)

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9 pages, 3147 KB

Open AccessCase Report

Molecular Detection of Tannerella forsythia in the Synovial Fluid of a Patient with Knee Osteoarthritis: A Case Report Suggesting Oral–Joint Translocation

by Ivana Milić, Mihovil Plečko, Domagoj Vražić, Domagoj Delimar and Ivan Puhar

Diagnostics 2026, 16(10), 1565; https://doi.org/10.3390/diagnostics16101565 - 21 May 2026

Abstract

Background and Clinical Significance: Tannerella forsythia is a Gram-negative, anaerobic bacterium primarily associated with severe periodontal disease. Extraoral infections are extremely rare, and the presence of Tannerella forsythia in synovial fluid has not been reported previously. Case Presentation: We report a case [...] Read more.

Background and Clinical Significance: Tannerella forsythia is a Gram-negative, anaerobic bacterium primarily associated with severe periodontal disease. Extraoral infections are extremely rare, and the presence of Tannerella forsythia in synovial fluid has not been reported previously. Case Presentation: We report a case of a 60-year-old female with grade IV primary osteoarthritis referred for dental evaluation. Clinical and radiographic examination revealed stage IV generalized periodontitis. Subgingival plaque samples were collected after non-surgical periodontal therapy and analyzed using a semi-quantitative real-time PCR targeting the 16S rRNA gene. During planned knee surgery, synovial fluid was obtained and processed using the same molecular protocol. PCR analysis of samples from the deepest periodontal pockets and synovial fluid confirmed the presence of Tannerella forsythia, demonstrating its potential dissemination from oral to joint tissues. The postoperative course was uneventful, with no signs of joint infection. Conclusions: To the best of our knowledge, this is the first reported detection of Tannerella forsythia in the synovial fluid of a patient with osteoarthritis, supporting the possibility of oral–joint microbial translocation. This finding should be interpreted with caution, as the detection of bacterial DNA does not indicate viability or causative involvement. More research is necessary to clarify the mechanisms underlying this association. Full article

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

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15 pages, 894 KB

Open AccessArticle

Translation, Cultural Adaptation, and Psychometric Validation of the Premenstrual Symptoms Screening Tool (PSST) in Serbian

by Dejan Mihajlovic, Momir Dunjic, Nenad Sulovic, Leonida Vitkovic, Kristina Brajovic Car, Radomir Anicic, Jovana Kocic, Nikolia Milijevic, Marija Milic and Jelena Dotlic

Diagnostics 2026, 16(10), 1564; https://doi.org/10.3390/diagnostics16101564 - 21 May 2026

Abstract

Background/Objectives: The signs and symptoms of premenstrual syndrome (PMS) can be similar to those of various other illnesses and conditions. To facilitate the detection and categorization of PMS symptoms, specific questionnaires have been developed. The aim of this study was to translate and [...] Read more.

Background/Objectives: The signs and symptoms of premenstrual syndrome (PMS) can be similar to those of various other illnesses and conditions. To facilitate the detection and categorization of PMS symptoms, specific questionnaires have been developed. The aim of this study was to translate and culturally adapt the Premenstrual Symptoms Screening Tool (PSST) for the Serbian-speaking population and assess its validity and reliability. Material and Methods: Our convenience sample included 350 Serbian-speaking female health sciences students from one of the Serbian universities who had PMS symptoms at least once during the past 12 months. They completed a general socio-epidemiologic questionnaire, the PSST, and the Depression, Anxiety and Stress Scale-21 (DASS-21). The PSST was translated according to the recommended methodology, and its psychometric characteristics (internal consistency, construct, discriminant validity and convergent validity) were tested. Results: There were no major changes in the items during the process of translation or validation. The Cronbach’s alpha coefficient for the whole scale was 0.927, whereas if an item was deleted, it was >0.8 for all the items. The McDonald’s omega coefficient was 0.896, indicating good internal consistency. The CI–TC coefficients were greater than 0.40 for all the items, indicating that all items were significant elements of the PSST. Exploratory factor analysis extracted three factors. Confirmatory factor analysis revealed adequate values for all model fit estimators. The PSST significantly correlated with the DASS-21, which confirmed its adequate convergent validity. Conclusions: The Serbian version of the PSST showed good validity and therefore can be used as a screening tool for PMS in Serbian-speaking young women. Full article

(This article belongs to the Special Issue Diagnostic Advances in Obstetrics and Gynecology, Breast Disease and Women’s Health)

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14 pages, 898 KB

Open AccessReview

Prevalence and Etiopathogenic Profile of Oral Squamous Cell Carcinoma in Nonsmokers and Nondrinkers: Expanding Risk Determinants Beyond Tobacco Exposure

by Effimia Stergiadou, Alexandros Louizakis, Dimitris Tatsis, Asterios Antoniou, Konstantinos Poulopoulos and Athanasios Poulopoulos

Diagnostics 2026, 16(10), 1563; https://doi.org/10.3390/diagnostics16101563 - 21 May 2026

Abstract

Oral squamous cell carcinoma (OSCC), comprising ~90% of oral malignancies, remains a major global health burden with rising incidence despite declining tobacco use. While tobacco and alcohol are classic dominant risk factors, a distinct subgroup of nonsmoking, nondrinking (NSND) patients is increasingly recognized, [...] Read more.

Oral squamous cell carcinoma (OSCC), comprising ~90% of oral malignancies, remains a major global health burden with rising incidence despite declining tobacco use. While tobacco and alcohol are classic dominant risk factors, a distinct subgroup of nonsmoking, nondrinking (NSND) patients is increasingly recognized, accounting for 15–35% of OSCC cases in many cohorts, particularly in developed countries. This emerging epidemic shows striking demographic patterns: strong female predominance (often 65–77% of cases), bimodal age distribution with peaks in young adults (<45 years) and elderly individuals (>70 years), and overrepresentation among non-Hispanic White and certain Asian populations. Unlike traditional habit-related OSCC, which favors the floor of the mouth in older males, NSND tumors predominantly arise on the lateral tongue, gingiva, and buccal mucosa. Etiopathogenesis extends far beyond conventional carcinogens and involves multifactorial mechanisms, including chronic mechanical irritation from dental factors, oral microbiome dysbiosis enriched with periodontal pathogens (e.g., Fusobacterium nucleatum and Porphyromonas gingivalis), limited roles for viruses (minimal HPV contribution, possible EBV or “hit-and-run” HSV effects), genetic susceptibilities (e.g., Fanconi anemia and CDKN2A mutations), epigenetic changes, hormonal influences contributing to female bias, metabolic conditions (diabetes and hyperlipidemia), poor oral hygiene, and chronic inflammation. NSND OSCC frequently exhibits a distinct immunological profile with higher tumor-infiltrating lymphocytes and PD-L1 expression, potentially favoring immunotherapy, though prognosis remains heterogeneous—better in some cohorts due to fewer comorbidities, yet worse in young patients with higher recurrence and second primary tumor risks. Delayed diagnosis is common due to low suspicion in “low-risk” individuals. This review underscores NSND OSCC as a unique entity requiring expanded risk assessment, heightened clinical vigilance for persistent oral lesions regardless of habit history, and targeted research into novel prevention and therapeutic strategies. Full article

(This article belongs to the Special Issue Diagnosis and Management in Oral and Maxillofacial Surgery)

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12 pages, 503 KB

Open AccessArticle

Impact of Prior Diabetic Retinal Screening on Hospitalization and Ophthalmic Follow-Up in Diabetic Patients with Newly Diagnosed Proliferative Diabetic Retinopathy

by Charles Zhang, Neel R. Sonik, Zoe J. Tsoukas, Jonathan B. Lin, Georges AbouKasm, Jason C. Fan and Ninel Z. Gregori

Diagnostics 2026, 16(10), 1562; https://doi.org/10.3390/diagnostics16101562 - 21 May 2026

Abstract

Background/Objectives: This retrospective cohort study compared hospitalization and follow-up rates in patients with newly diagnosed proliferative diabetic retinopathy (PDR) versus those without prior diabetic retinopathy (DR) screening. Methods: Using TriNetX, a global electronic health record database, 57,964 patients aged ≥ 40 years [...] Read more.

Background/Objectives: This retrospective cohort study compared hospitalization and follow-up rates in patients with newly diagnosed proliferative diabetic retinopathy (PDR) versus those without prior diabetic retinopathy (DR) screening. Methods: Using TriNetX, a global electronic health record database, 57,964 patients aged ≥ 40 years with type 2 diabetes and newly diagnosed PDR without diabetic macular edema (DME) requiring panretinal photocoagulation or intravitreal injection were included. Patients were stratified based on the presence or absence of prior DR screening in the last 5 years and balanced using propensity score matching (PSM). Primary outcomes included 30-, 60-, and 90-day hospitalization rates and repeat ophthalmic follow-up as estimated using repeat PDR diagnosis codes and repeat retinal imaging codes, including OCT, fundus photography, and fluorescein angiography. Results: Of 57,964 patients, 25,003 had no prior DR screening and 32,961 had prior DR screening. After matching, 19,316 patients were included per cohort. Patients without known DR screening had significantly higher hospitalization rates at 30 days (RR = 1.78, 95% CI 1.67–1.89), 60 days (RR = 1.59, 95% CI 1.51–1.67), and 90 days (RR = 1.51, 95% CI 1.44–1.58), and lower repeat ophthalmic visits by PDR codes at 30 days (RR = 0.458, 95% CI 0.440–0.476), 60 days (RR = 0.450, 95% CI 0.437–0.463) and 90 days (RR = 0.420, 95% CI 0.408–0.432) or by repeat retinal imaging codes at 30 days (RR = 0.450, 95% CI 0.423–0.478), 60 days (RR = 0.394, 95% CI 0.377–0.411), and 90 days (RR = 0.381, 95% CI 0.366–0.396) (all p < 0.0001). Conclusions: Absence of known prior DR screening in PDR patients is associated with higher hospitalization risk and reduced ophthalmic follow-up, suggesting that a lack of screening indicates broader gaps in healthcare engagement and disease control. Tailored strategies are needed to prevent vision loss as well as systemic complications. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis and Prognosis of Eye Diseases)

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15 pages, 643 KB

Open AccessArticle

Predictive Value of the CALLY Index for Interventional Management in Vaginal Cuff Hematoma Following Hysterectomy

by Candost Hanedan, Ayşe Nur İnal, Ayşe Yiğit, Oğuz Kaan Köksal, Şahin Kaan Baydemir, Neslihan Öztürk, Hande Nur Öncü, Gökçen Ege, Aysu Yeşim Tezcan, Tuba Zengin Aksel, Vakkas Korkmaz and Çağanay Soysal

Diagnostics 2026, 16(10), 1561; https://doi.org/10.3390/diagnostics16101561 - 21 May 2026

Abstract

Background/Objectives: Vaginal cuff hematoma is a recognized complication following hysterectomy, with a subset of patients requiring invasive intervention. No reliable bedside biomarker currently exists to identify at admission patients likely to fail conservative management. This study aimed to evaluate the incidence and clinical [...] Read more.

Background/Objectives: Vaginal cuff hematoma is a recognized complication following hysterectomy, with a subset of patients requiring invasive intervention. No reliable bedside biomarker currently exists to identify at admission patients likely to fail conservative management. This study aimed to evaluate the incidence and clinical characteristics of symptomatic vaginal cuff hematoma across all hysterectomy approaches, and to assess the predictive performance of the CALLY index (CRP-albumin-lymphocyte index), a composite marker of inflammatory burden, immune function, and nutritional status, alongside the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) for identifying patients requiring interventional management. Methods: This retrospective cohort study included 61 patients with symptomatic vaginal cuff hematoma following hysterectomy in a major tertiary referral center (November 2022–July 2025). Patients were divided into conservative (n = 38) and interventional (n = 23) management groups. The CALLY index was calculated as [Albumin (g/dL) × Lymphocyte (×10⁹/L)] ÷ [CRP (mg/L) × 10⁻²]. Receiver operating characteristic (ROC) curve analysis with the DeLong method was used to compare predictive performance. Results: The overall incidence of symptomatic vaginal cuff hematoma was 1.9% (73/3852 hysterectomies), with the highest rate following vaginal hysterectomy (3.32%) and the lowest after robotic hysterectomy (0.74%). Interventional management was required in 37.7% of patients. The interventional group had significantly higher CRP (192 vs. 62 mg/L, p < 0.001), NLR (7.53 vs. 4.17, p < 0.001), and SII (2308 vs. 1207, p < 0.001), and significantly lower CALLY index values (2.00 vs. 9.80, p < 0.001). The CALLY index demonstrated the highest predictive performance (AUC = 0.863, 95% CI: 0.762–0.964), outperforming SII (AUC = 0.801), NLR (AUC = 0.789), and PLR (AUC = 0.654). At the optimal cutoff of ≤2.89, the CALLY index yielded a sensitivity of 65.2% and a specificity of 92.1%. Conclusions: The CALLY index is a simple, routinely available composite biomarker that may help identify patients at higher risk for interventional management in symptomatic vaginal cuff hematoma. Its incorporation into postoperative assessment may improve risk stratification and support timely clinical decision-making. Full article

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

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13 pages, 2587 KB

Open AccessArticle

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

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

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

Abstract

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

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

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

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17 pages, 727 KB

Open AccessArticle

A Hemodynamic Bridge from Echocardiography to Directly Measured Left Ventricular End-Diastolic Pressure: The Intermediate Role of Pulmonary Artery Diastolic Pressure in a Routine Catheterization Cohort

by Aykan Çelik, Tuncay Kiris, Harun Erdem, Semih Babacan and Cem Nazlı

Diagnostics 2026, 16(10), 1559; https://doi.org/10.3390/diagnostics16101559 - 20 May 2026

Abstract

Background: Noninvasive echocardiographic markers are widely used to estimate left ventricular filling pressure, but their relationship with directly measured left ventricular end-diastolic pressure (LVEDP) is often modest and context-dependent. Whether routinely available noninvasive findings reflect elevated LVEDP through an intermediate invasive pulmonary [...] Read more.

Background: Noninvasive echocardiographic markers are widely used to estimate left ventricular filling pressure, but their relationship with directly measured left ventricular end-diastolic pressure (LVEDP) is often modest and context-dependent. Whether routinely available noninvasive findings reflect elevated LVEDP through an intermediate invasive pulmonary hemodynamic phenotype remains insufficiently characterized. Objective: To evaluate the relationship of noninvasive echocardiographic and laboratory markers with directly measured LVEDP and to determine whether invasive pulmonary artery diastolic pressure (dPAP) functions as a hemodynamic bridge linking upstream noninvasive findings to elevated left ventricular filling pressure in a routine catheterization cohort. Methods: This retrospective single-center observational study included patients undergoing routine cardiac catheterization with available direct LVEDP measurement and invasive pulmonary artery pressure data. Elevated LVEDP was defined as LVEDP ≥ 15 mmHg, and elevated dPAP as dPAP ≥ 24 mmHg. Noninvasive, bridge, and invasive validation models were evaluated using logistic regression, receiver operating characteristic analysis, calibration assessment, and bootstrap internal validation. Results: A total of 75 patients had direct LVEDP data, 94 had invasive dPAP data, 83 had echocardiographic systolic pulmonary artery pressure (echo-sPAP), and 37 had pulmonary capillary wedge pressure (PCWP) measurements. Patients with elevated LVEDP had significantly higher creatinine (p = 0.026), dPAP (p = 0.043), and PCWP (p = 0.004). Echo-sPAP showed good discrimination for elevated dPAP, with an AUC of 0.791 (95% CI 0.695–0.888), supporting its role as an upstream noninvasive marker of invasive pulmonary hemodynamic burden. A noninvasive model combining echo-sPAP and creatinine showed modest discrimination for elevated LVEDP (AUC 0.664, 95% CI 0.522–0.806; Brier score 0.198), whereas an invasive validation model combining dPAP and creatinine showed better performance (AUC 0.734, 95% CI 0.617–0.850; Brier score 0.176). In bootstrap validation, the optimism-corrected AUCs were approximately 0.624 and 0.711, respectively. Although the invasive model performed numerically better, DeLong comparison did not show a statistically significant difference between the two models (p = 0.459). Conclusions: Routinely available noninvasive echocardiographic and laboratory findings appear to relate to directly measured left ventricular filling pressure through an intermediate invasive pulmonary hemodynamic pattern. Echo-sPAP showed its strongest signal at the level of elevated dPAP, whereas dPAP combined with creatinine provided the most informative model for elevated directly measured LVEDP. These findings support a hypothesis-generating hemodynamic framework linking noninvasive assessment to directly measured filling pressure and may help inform noninvasive hemodynamic triage and physiological risk enrichment in selected clinical settings. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management in Cardiology: 2nd Edition)

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Graphical abstract

18 pages, 2294 KB

Open AccessArticle

Diagnostic Value of Native T1 and T2 Mapping in Differentiating Clinically Suspected Amyloidosis and Hypertrophic Cardiomyopathy

by Sena Unal, Caglar Uzun, Sena Bozer Uludag, Cuneyt Yamak, Turkan Seda Tan and Elif Peker

Diagnostics 2026, 16(10), 1558; https://doi.org/10.3390/diagnostics16101558 - 20 May 2026

Abstract

Background/Objectives: Differentiating clinically suspected cardiac amyloidosis from hypertrophic cardiomyopathy (HCM) remains a significant clinical challenge, especially when contrast-enhanced imaging is contraindicated. This study evaluated the potential diagnostic utility of non-contrast cardiac MRI parameters, specifically native T1 and T2 mapping, as supportive indicators in [...] Read more.

Background/Objectives: Differentiating clinically suspected cardiac amyloidosis from hypertrophic cardiomyopathy (HCM) remains a significant clinical challenge, especially when contrast-enhanced imaging is contraindicated. This study evaluated the potential diagnostic utility of non-contrast cardiac MRI parameters, specifically native T1 and T2 mapping, as supportive indicators in this differential diagnosis. Methods: This retrospective single-center study included 20 patients with clinically suspected amyloidosis (based on combined clinical and echocardiographic assessment), 20 patients with HCM, and 20 healthy controls. Cine imaging and native T1/T2 mapping were analyzed. Myocardial, blood-pool, and liver T1/T2 values, along with morphological parameters, were recorded. N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin levels, when available, were documented retrospectively for descriptive purposes. Receiver operating characteristic (ROC) analyses were performed to assess the discriminatory performance of imaging parameters. Results: Patients in the suspected amyloidosis group demonstrated significantly higher myocardial, blood-pool, and liver T1 values, as well as higher myocardial T2 values, compared with both the HCM and control groups (p < 0.001). Myocardial T1 showed strong discriminatory performance for differentiating suspected amyloidosis from controls (cut-off 1061 ms, AUC = 0.975). In distinguishing suspected amyloidosis from HCM, blood-pool T1 (AUC = 0.900) and myocardial T1 (AUC = 0.938) provided the highest diagnostic performance. Additionally, elevated NT-proBNP (>1000 pg/mL in 93% of tested cases) and troponin levels were observed in the suspected amyloidosis group, consistent with increased myocardial stress. Conclusions: Native T1 and T2 mapping may offer valuable supportive information in differentiating clinically suspected amyloidosis from HCM on non-contrast MRI. Myocardial and blood-pool T1 values appear to provide complementary tissue characterization, which may be particularly useful when gadolinium administration or invasive procedures are not feasible. These findings suggest a role for non-contrast mapping in the diagnostic workup but require further validation in larger, biopsy-confirmed multicenter cohorts. Full article

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

19 pages, 1641 KB

Open AccessReview

From Angiosome to Woundosome: An Interdisciplinary Approach to Personalized Revascularization in Chronic Limb-Threatening Ischemia

by Mircea Ionut Popitiu, Lorenzo Patrone, Giacomo Clerici, Serban Comsa, Gloria Gavrila-Ardelean, Nilima Rajpal Kundnani, Nicu Olariu and Mihai Edmond Ionac

Diagnostics 2026, 16(10), 1557; https://doi.org/10.3390/diagnostics16101557 - 20 May 2026

Abstract

Background/Objectives: Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral arterial disease and is associated with high rates of major amputation and mortality. The angiosome concept has become an important tool for planning targeted revascularization. However, its clinical value may [...] Read more.

Background/Objectives: Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral arterial disease and is associated with high rates of major amputation and mortality. The angiosome concept has become an important tool for planning targeted revascularization. However, its clinical value may be limited in patients with complex arterial disease, impaired collateral circulation, and microvascular dysfunction. This review explores the relationship between angiosome-guided revascularization and the emerging woundosome concept, which focuses on functional wound perfusion. Methods: A narrative review with a structured literature search was performed using PubMed/MEDLINE, Scopus, and Web of Science. Studies evaluating angiosome-guided revascularization, direct versus indirect revascularization, collateral circulation, pedal arch integrity, and perfusion-related outcomes in CLTI and diabetic foot disease were included. Results: Most observational studies and meta-analyses suggest that direct angiosome-targeted revascularization may improve wound healing and limb salvage in selected patients. However, clinical outcomes are also influenced by collateral circulation, anatomical variability, infra-malleolar perfusion, pedal arch integrity, and microvascular function. The woundosome concept expands the traditional angiosome model by emphasizing effective perfusion of the wound bed through direct arterial inflow, collateral pathways, and functional perfusion assessment. Conclusions: Combining the angiosome and woundosome concepts may provide a more practical and individualized approach to revascularization planning in CLTI by integrating anatomical vascular mapping with functional wound perfusion assessment. Full article

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

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6 pages, 8240 KB

Open AccessInteresting Images

Ultrasonography for Surgical Planning and Follow-Up in Neurofibromatosis Type 1

by Po-Yin Shen, Cheng-Jung Ho, Wei-Ting Wu, Ke-Vin Chang and Levent Özçakar

Diagnostics 2026, 16(10), 1556; https://doi.org/10.3390/diagnostics16101556 - 20 May 2026

Abstract

Ultrasonography can assist in the preoperative evaluation and postoperative surveillance of superficial soft tissue tumors of the hand. We present an ultrasound-based identification of a neurofibroma in a patient with neurofibromatosis type 1 (NF1). A 45-year-old male presented with a slowly enlarging subcutaneous [...] Read more.

Ultrasonography can assist in the preoperative evaluation and postoperative surveillance of superficial soft tissue tumors of the hand. We present an ultrasound-based identification of a neurofibroma in a patient with neurofibromatosis type 1 (NF1). A 45-year-old male presented with a slowly enlarging subcutaneous mass over the dorsal aspect of the hand associated with localized paresthesia. Physical examination revealed characteristic NF1 stigmata, including café-au-lait macules, axillary freckling, and craniofacial asymmetry suggestive of sphenoid wing dysplasia. High-resolution ultrasonography demonstrated a well-defined hypoechoic fusiform lesion along the course of a digital nerve, suggestive of a peripheral nerve sheath tumor. Magnetic resonance imaging showed a T2-hyperintense lesion compatible with a nerve sheath tumor. Surgical excision was subsequently performed, and histopathological examination confirmed a localized neurofibroma with incorporation of native nerve fascicles within a myxoid spindle cell matrix. Serial postoperative ultrasonography at 3 and 12 months demonstrated no evidence of local recurrence. This case highlights ultrasonography as a practical, radiation-free, and cost-effective modality for both preoperative assessment and longitudinal follow-up of superficial NF1-associated neurofibromas. Full article

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

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31 pages, 6077 KB

Open AccessReview

Optical Coherence Tomography Biomarkers Predicting Progression to Atrophy in Non-Exudative Age-Related Macular Degeneration

by Aleksandra Prus-Ludwig, Adam Wylęgała, Edward Wylęgała, Magdalena Kijonka and Bogumił Wowra

Diagnostics 2026, 16(10), 1555; https://doi.org/10.3390/diagnostics16101555 - 20 May 2026

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Geographic atrophy (GA) is an advanced, currently incurable stage of non-exudative AMD and is characterized by progressive atrophy of the retinal pigment epithelium and outer retina, resulting in substantial visual [...] Read more.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Geographic atrophy (GA) is an advanced, currently incurable stage of non-exudative AMD and is characterized by progressive atrophy of the retinal pigment epithelium and outer retina, resulting in substantial visual impairment. Optical coherence tomography (OCT) has revolutionized the diagnosis and monitoring of AMD by enabling in vivo visualization of retinal microstructure and identification of imaging biomarkers associated with progression to late-stage disease. Improved understanding of these lesions may clarify disease pathogenesis and inform the development of new therapeutic strategies and clinical trial endpoints. This review summarizes OCT-based biomarkers reported as predictors of progression to late atrophic forms of AMD, with emphasis on early atrophic changes that precede GA. Full article

(This article belongs to the Special Issue Eye Disease: Diagnosis, Management, and Prognosis—2nd Edition)

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