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Diagnostics
Volume 13
Issue 24
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Diagnostics, Volume 13, Issue 24 (December-2 2023) – 92 articles

Cover Story (view full-size image): Accurately predicting stroke recovery outcomes, measured by the modified Rankin Scale (mRS), from brain CT scans remains challenging yet clinically valuable. We tested deep learning models to predict a patient's mRS at 3 months post-stroke. We experimented with image-only models that make predictions directly from CT scans, and hybrid models that incorporate clinical and demographic information along with imaging data. In the hybrid models, we first extracted quantitative imaging biomarkers reflective of stroke damage from CT scans using deep learning. These imaging features were then incorporated into prognostic machine learning models for making outcome predictions. This approach could help address the challenges faced by image-only approach and also make the resulting model more interpretable. View this paper
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14 pages, 3260 KiB  
Article
Impact of Voxel Normalization on a Machine Learning-Based Method: A Study on Pulmonary Nodule Malignancy Diagnosis Using Low-Dose Computed Tomography (LDCT)
by Chia-Chi Hsiao, Chen-Hao Peng, Fu-Zong Wu and Da-Chuan Cheng
Diagnostics 2023, 13(24), 3690; https://doi.org/10.3390/diagnostics13243690 - 18 Dec 2023
Cited by 1 | Viewed by 1834
Abstract
Lung cancer (LC) stands as the foremost cause of cancer-related fatality rates worldwide. Early diagnosis significantly enhances patient survival rate. Nowadays, low-dose computed tomography (LDCT) is widely employed on the chest as a tool for large-scale lung cancer screening. Nonetheless, a large amount [...] Read more.
Lung cancer (LC) stands as the foremost cause of cancer-related fatality rates worldwide. Early diagnosis significantly enhances patient survival rate. Nowadays, low-dose computed tomography (LDCT) is widely employed on the chest as a tool for large-scale lung cancer screening. Nonetheless, a large amount of chest radiographs creates an onerous burden for radiologists. Some computer-aided diagnostic (CAD) tools can provide insight to the use of medical images for diagnosis and can augment diagnostic speed. However, due to the variation in the parameter settings across different patients, substantial discrepancies in image voxels persist. We found that different voxel sizes can create a compromise between model generalization and diagnostic efficacy. This study investigates the performance disparities of diagnostic models trained on original images and LDCT images reconstructed to different voxel sizes while making isotropic. We examined the ability of our method to differentiate between benign and malignant nodules. Using 11 features, a support vector machine (SVM) was trained on LDCT images using an isotropic voxel with a side length of 1.5 mm for 225 patients in-house. The result yields a favorable model performance with an accuracy of 0.9596 and an area under the receiver operating characteristic curve (ROC/AUC) of 0.9855. In addition, to furnish CAD tools for clinical application, future research including LDCT images from multi-centers is encouraged. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>PNs Presentation. The red contours are manual delineations on nodules. (<b>A</b>) and (<b>B</b>) depict benign PNs, while (<b>C</b>) and (<b>D</b>) show malignant PNs.</p> Full article ">Figure 2
<p>Experimental flowchart of this study.</p> Full article ">Figure 3
<p><span class="html-italic">p</span>-value distribution of radiomics features extracted from voxels with different side lengths reconstructed from raw LDCT data. This experiment aimed to examine the feature efficacy of benign and malignant nodule classification, based on different voxel sizes.</p> Full article ">Figure 4
<p>Model performance comparison of three feature selection methods and a baseline.</p> Full article ">Figure 5
<p>Distribution plot of 11 features extracted from PNs with a voxel with a side length of 1.5 mm after dimension reduction using t-SNE.</p> Full article ">Figure 6
<p>Model performance for reconstructed data with various side lengths.</p> Full article ">Figure 7
<p>Ten-fold cross-validation ROC curve for the model trained with 11 features selected by LASSO with a voxel with a side length of 1.5 mm. Note that some lines are overlapping.</p> Full article ">
12 pages, 285 KiB  
Review
Clinical Diagnosis and Treatment of Chronic Pain
by Sadiq Rahman, Ali Kidwai, Emiliya Rakhamimova, Murad Elias, William Caldwell and Sergio D. Bergese
Diagnostics 2023, 13(24), 3689; https://doi.org/10.3390/diagnostics13243689 - 18 Dec 2023
Cited by 3 | Viewed by 3111
Abstract
More than 600 million people globally are estimated to be living with chronic pain. It is one of the most common complaints seen in an outpatient setting, with over half of patients complaining of pain during a visit. Failure to properly diagnose and [...] Read more.
More than 600 million people globally are estimated to be living with chronic pain. It is one of the most common complaints seen in an outpatient setting, with over half of patients complaining of pain during a visit. Failure to properly diagnose and manage chronic pain is associated with substantial morbidity and mortality, especially when opioids are involved. Furthermore, it is a tremendous financial strain on the healthcare system, as over USD 100 billion is spent yearly in the United States on healthcare costs related to pain management and opioids. This exceeds the costs of diabetes, heart disease, and cancer-related care combined. Being able to properly diagnose, manage, and treat chronic pain conditions can substantially lower morbidity, mortality, and healthcare costs in the United States. This review will outline the current definitions, biopsychosocial model, subclassifications, somatosensory assessments, imaging, clinical prediction models, and treatment modalities associated with chronic pain. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Chronic Pain)
12 pages, 985 KiB  
Article
Performance Evaluation of Three Antibody Binding Assays, a Neutralizing Antibody Assay, and an Interferon-Gamma Release Assay for SARS-CoV-2 According to Vaccine Type in Vaccinated Group
by Minjeong Nam, Jae Hyun Cha, Sang-Wook Kim, Sun Bean Kim, Ki-Byung Lee, You-Seung Chung, Seung Gyu Yun, Myung-Hyun Nam, Chang Kyu Lee and Yunjung Cho
Diagnostics 2023, 13(24), 3688; https://doi.org/10.3390/diagnostics13243688 - 18 Dec 2023
Viewed by 1163
Abstract
We evaluated the performance of SARS-CoV-2 assays in the vaccinated group using receptor-binding domain antibody assays (RBD Ab assay), neutralizing antibody assay (nAb assay), and interferon-gamma release assay (IGR assay). We also compared the performance of the SARS-CoV-2 assays based on vaccine type [...] Read more.
We evaluated the performance of SARS-CoV-2 assays in the vaccinated group using receptor-binding domain antibody assays (RBD Ab assay), neutralizing antibody assay (nAb assay), and interferon-gamma release assay (IGR assay). We also compared the performance of the SARS-CoV-2 assays based on vaccine type in a large population. We collected 1851 samples from vaccinated individuals with vector, mix-and-match (MM), and mRNA vaccines. The performance of the RBD Ab assays was assessed by SARS-CoV-2 IgG II Quant (Abbott Laboratories, Sligo, Ireland), SARS-CoV-2 IgG (Beckman Coulter, CA, USA), and anti-SARS-CoV-2 S (Roche Diagnostics GmbH, Mannheim, Germany). The nAb assay was assessed by cPass SARS-CoV-2 neutralization antibody detection kits (GenScript, NJ, USA). The IGR assay was assessed by QuantiFERON (Qiagen, Venlo, The Netherlands). Median values of the RBD Ab assays and nAb assay sequentially increased after the first and second vaccinations. RBD Ab assays and nAb assay showed very strong correlations. The median values of the RBD Ab, nAb, and IGR were higher in the mRNA vaccine group than in the vector and MM vaccine groups. The agreement and correlation among the RBD Ab assays, nAb assay, and IGR assay were higher in the mRNA vaccine group than in the vector and MM vaccine groups. We compared the performance of the RBD Ab assay, nAb assay, and IGR assay based on the vaccine types using the RBD Ab, nAb, and IGR assays. This study provides a better understanding of the assessment of humoral and cellular immune responses after vaccination. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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<p>Quantitative correlation among the RBD Ab assays and nAb assay. (<b>A</b>) RBD Ab_A vs. RBD Ab_B, (<b>B</b>) RBD Ab_A vs. RBD Ab_R, and (<b>C</b>) RBD Ab_B vs. RBD Ab_R. The black line indicates the regression line of the vaccinated group. (<b>D</b>) RBD Ab_A, (grey triangle and dotted grey line) (<b>E</b>) RBD Ab_B (empty circle and solid grey line), and (<b>F</b>) RBD Ab_R (filled circle and solid black line) were compared with the nAb assay. Abbreviations: RBD Ab, receptor-binding domain antibodies; BAU, binding antibody units.</p> Full article ">Figure 2
<p>Quantitative correlation according to vaccine type among the RBD Ab assays and nAb assay. (<b>A</b>) RBD Ab_A vs. RBD Ab_B, (<b>B</b>) RBD Ab_A vs. RBD Ab_R, and (<b>C</b>) RBD Ab_B vs. RBD Ab_R were compared according to vaccine among BRD Ab assays. nAb assay was compared with (<b>D</b>) RBD Ab_A, (<b>E</b>) RBD Ab_B, and (<b>F</b>) RBD Ab_R. IGR assay was compared with (<b>G</b>) RBD Ab_A, (<b>H</b>) RBD Ab_B, (<b>I</b>) RBD Ab_R, and (<b>J</b>) the nAb assay. The regression lines were presented by the grey dotted line for vector vaccine, the grey solid for MM vaccines, and the black solid line for mRNA vaccine groups.</p> Full article ">
14 pages, 1653 KiB  
Article
Comparison of Automated Keratometer and Scheimpflug Tomography for Predicting Refractive Astigmatism in Pseudophakic Eyes
by Kyung-Sun Na, Giacomo Savini, Woong-Joo Whang and Kristian Næser
Diagnostics 2023, 13(24), 3687; https://doi.org/10.3390/diagnostics13243687 - 18 Dec 2023
Viewed by 1025
Abstract
Purpose: To analyse the correspondence between refractive astigmatism and corneal astigmatism in pseudophakic eyes with non-toric intraocular lenses. Setting: Yeouido St. Mary hospital, Seoul, Republic of Korea. Design: Evaluation of a diagnostic test instrument. Methods: This retrospective study included 95 eyes of 95 [...] Read more.
Purpose: To analyse the correspondence between refractive astigmatism and corneal astigmatism in pseudophakic eyes with non-toric intraocular lenses. Setting: Yeouido St. Mary hospital, Seoul, Republic of Korea. Design: Evaluation of a diagnostic test instrument. Methods: This retrospective study included 95 eyes of 95 patients. Corneal astigmatism was measured with an automated keratometer (RK-5, Canon) and Scheimpflug tomography (Pentacam HR, Oculus). Refractive astigmatism was compared to keratometric astigmatism (based on anterior corneal measurements only), equivalent K-reading, and total corneal astigmatism (both based on anterior and posterior corneal measurements). Vector analysis was carried out by Næser’s polar value method. The accuracy was defined as the average magnitude of the vectorial difference in astigmatism (DA). Each corneal measurement was optimized in retrospect by a multiple linear regression equation between refractive and corneal astigmatism. Results: Keratometric astigmatism overestimated with-the-rule (WTR) refractive astigmatism and underestimated against-the-rule (ATR) refractive astigmatism. Several measurements based on both corneal surfaces’ values did not show any statistically significant difference with respect to refractive astigmatism. The mean corneal astigmatism by total corneal refractive power (TCRP) at 4.0 mm (zone/pupil) produced the lowest mean arithmetic DA and the highest percentage of eyes with a DA ≤ 0.50 dioptre. After optimization, the accuracies of automated KA and TCRP 4.0 mm (zone/pupil) were similar. Conclusions: Total corneal astigmatism measured by Scheimpflug tomography at a 4.0 mm zone centered on the pupil accurately reflects the refractive astigmatism in pseudophakic eyes. However, the accuracy of total corneal astigmatism is not different from automated KA after optimization. Full article
(This article belongs to the Special Issue Applications of Optical Coherence Tomography in the Ocular Diagnosis 2.0)
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<p>Mean DA magnitudes in a whole sample and three subgroups divided according to the orientation of the steep meridian.</p> Full article ">Figure 2
<p>Difference between refractive and corneal astigmatism on double angle polar plots <span class="html-italic">before</span> optimization. Individual values and combined means (centroids) with their 95% confidence ellipses. DAs were derived from (<b>A</b>) the automated keratometer and (<b>B</b>) Scheimpflug TCRP 4.0 mm zone centred on pupil.</p> Full article ">Figure 3
<p>Difference between refractive and corneal astigmatism on double angle polar plots <span class="html-italic">after</span> optimization. Legend as for <a href="#diagnostics-13-03687-f001" class="html-fig">Figure 1</a>. Following optimization, the cluster of points and centroids were more centred on the coordinate origin, and the extension of the confidence ellipses diminished, thereby signifying increased accuracy.</p> Full article ">
10 pages, 900 KiB  
Brief Report
Performance of a Point-of-Care Fluorescence Immunoassay Test to Measure the Anti-Severe Acute Respiratory Syndrome Corona Virus 2 Spike, Receptor Binding Domain Antibody Level
by Marita Restie Tiara, Hofiya Djauhari, Febi Ramdhani Rachman, Antonius Christianus Rettob, Darmastuti Utami, Fahda Cintia Suci Pulungan, Heru Purwanta, Rudi Wisaksana, Bachti Alisjahbana and Agnes Rengga Indrati
Diagnostics 2023, 13(24), 3686; https://doi.org/10.3390/diagnostics13243686 - 18 Dec 2023
Cited by 2 | Viewed by 1075
Abstract
Quantitative determination of anti-SARS-CoV2-S-RBD is necessary for the evaluation of vaccination effectiveness. The surrogate viral neutralization test (SVNT) is approved for measuring anti-SARS-CoV2-S-RBD, but a point-of-care platform is needed to simplify anti-SARS-CoV-2-S-RBD measurement. We aimed to evaluate the performance of a rapid fluorescent [...] Read more.
Quantitative determination of anti-SARS-CoV2-S-RBD is necessary for the evaluation of vaccination effectiveness. The surrogate viral neutralization test (SVNT) is approved for measuring anti-SARS-CoV2-S-RBD, but a point-of-care platform is needed to simplify anti-SARS-CoV-2-S-RBD measurement. We aimed to evaluate the performance of a rapid fluorescent immunoassay-based kit, FastBio-RBDTM, compared to the SVNT. During April–September 2021, we enrolled two groups of subjects, convalescent subjects and subjects without a COVID-19 history. The subjects were tested for the anti-SARS-CoV2-S-RBD antibody using FastBio-RBDTM and the GenScript-cPASSTM SVNT. We measured the correlation coefficient and conducted an ROC analysis to determine the best cut-off value of anti-SARS-CoV2-S-RBD against the SVNT percent inhibition levels of 30% and 60%. We included 109 subjects. Anti-SARS-CoV-2-S-RBD strongly correlated to SVNT % inhibition with an R value of 0.866 (p < 0.0001). The ROC analysis showed that the anti-SARS-CoV-2-S-RBD of 6.71 AU/mL had 95.7% sensitivity and 87.5% specificity to detect a percentage inhibition of 30%. The anti-SARS-CoV-2-S-RBD of 59.76 AU/mL had a sensitivity of 88.1% and specificity of 97.0% to detect a percentage inhibition of 60%. FastBio-RBDTM could determine the presence and level of anti-SARS-CoV-2-S-RBD with good sensitivity and specificity. It has the potential to be deployed in health facilities with limited resources. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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<p>(<b>a</b>) Distribution of anti-S-RBD antibody levels among all subjects. The graph represents a plot of the results, and the horizontal line depicts the median values. * <span class="html-italic">p</span> value ≥ 0.05, ** <span class="html-italic">p</span>-value &lt; 0.05. (<b>b</b>) Distribution of the surrogate viral neutralization percent inhibition among all subjects. The graph represents a plot of the results. The horizontal lines depict the median values. * <span class="html-italic">p</span> value ≥ 0.05, ** <span class="html-italic">p</span>-value &lt; 0.05.</p> Full article ">Figure 1 Cont.
<p>(<b>a</b>) Distribution of anti-S-RBD antibody levels among all subjects. The graph represents a plot of the results, and the horizontal line depicts the median values. * <span class="html-italic">p</span> value ≥ 0.05, ** <span class="html-italic">p</span>-value &lt; 0.05. (<b>b</b>) Distribution of the surrogate viral neutralization percent inhibition among all subjects. The graph represents a plot of the results. The horizontal lines depict the median values. * <span class="html-italic">p</span> value ≥ 0.05, ** <span class="html-italic">p</span>-value &lt; 0.05.</p> Full article ">Figure 2
<p>Spearman’s correlation between the anti-S-RBD antibody level to the surrogate viral neutralization test % inhibition among all subjects.</p> Full article ">
13 pages, 2898 KiB  
Article
Immunohistochemical Stain-Aided Annotation Accelerates Machine Learning and Deep Learning Model Development in the Pathologic Diagnosis of Nasopharyngeal Carcinoma
by Tai-Pei Lin, Chiou-Ying Yang, Ko-Jiunn Liu, Meng-Yuan Huang and Yen-Lin Chen
Diagnostics 2023, 13(24), 3685; https://doi.org/10.3390/diagnostics13243685 - 18 Dec 2023
Cited by 1 | Viewed by 1477
Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial cancer originating in the nasopharynx epithelium. Nevertheless, annotating pathology slides remains a bottleneck in the development of AI-driven pathology models and applications. In the present study, we aim to demonstrate the feasibility of using immunohistochemistry (IHC) for [...] Read more.
Nasopharyngeal carcinoma (NPC) is an epithelial cancer originating in the nasopharynx epithelium. Nevertheless, annotating pathology slides remains a bottleneck in the development of AI-driven pathology models and applications. In the present study, we aim to demonstrate the feasibility of using immunohistochemistry (IHC) for annotation by non-pathologists and to develop an efficient model for distinguishing NPC without the time-consuming involvement of pathologists. For this study, we gathered NPC slides from 251 different patients, comprising hematoxylin and eosin (H&E) slides, pan-cytokeratin (Pan-CK) IHC slides, and Epstein–Barr virus-encoded small RNA (EBER) slides. The annotation of NPC regions in the H&E slides was carried out by a non-pathologist trainee who had access to corresponding Pan-CK IHC slides, both with and without EBER slides. The training process utilized ResNeXt, a deep neural network featuring a residual and inception architecture. In the validation set, NPC exhibited an AUC of 0.896, with a sensitivity of 0.919 and a specificity of 0.878. This study represents a significant breakthrough: the successful application of deep convolutional neural networks to identify NPC without the need for expert pathologist annotations. Our results underscore the potential of laboratory techniques to substantially reduce the workload of pathologists. Full article
(This article belongs to the Special Issue Applications of Artificial Intelligence in Healthcare Monitoring)
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<p>The study design of the current study. NPC, nasopharyngeal carcinoma; Pan-CK, pan-cytokeratin antibody; EBER, Epstein–Barr virus in situ hybridization.</p> Full article ">Figure 2
<p>Representative pictures of nasopharyngeal carcinoma and corresponding Pan-CK immunohistochemical stain. Representative pictures of nasopharyngeal carcinoma in H&amp;E stain (<b>A</b>,<b>C</b>) and corresponding Pan-CK immunohistochemical stain (<b>B</b>,<b>D</b>). The easier case with NPC cells (red asterisks) in a large pale morphology in H&amp;E slide (<b>A</b>) and highlighted by Pan-CK IHC stain (<b>B</b>). Harder NPC cases with NPC cells infiltrating (red circle) in the stroma in a small nest showed in the H&amp;E slide (<b>C</b>) and also highlighted by Pan-CK IHC stain (<b>D</b>). All figures are in 100× magnification.</p> Full article ">Figure 3
<p>Representative pictures of difficult nasopharyngeal carcinoma case with H&amp;E stain and corresponding Pan-CK immunohistochemical stain and EBER stain. Representative pictures of difficult nasopharyngeal carcinoma cases, with mostly single or tiny tumor nests (red arrows) in H&amp;E stain (<b>A</b>) and corresponding Pan-CK IHC (<b>B</b>) and EBER stain (<b>C</b>). All figures are in 100× magnification.</p> Full article ">Figure 4
<p>Representative pictures of free-hand region-of-interest labelling in nasopharyngeal carcinoma slides. The non-pathologist trainee label the NPC area in a free-hand region-of-interest style for NPC areas (green dots area). They labelled the NPC area by simultaneous the area of pan-CK IHC slides with/without EBER slides.</p> Full article ">Figure 5
<p>The representative pictures of different size of the patch and model design. The representative NPC cells size in different patch size of 1000 × 1000, 400 × 400, and 200 × 200 (<b>A</b>). In our patch-level training, testing, and validation procedures, we employed square image patches with dimensions of 400 × 400 pixels. These patches were randomly and dynamically cropped from the areas that were free-hand annotated. (<b>B</b>). Our training utilized ResNeXt, a deep neural network architecture incorporating both residual and inception features. During training, we employed a batch size of 48 patches, consisting of 24 patches for NPC and 24 patches for benign tissue.</p> Full article ">Figure 6
<p>The training history of the train set and test set. The training history of the accuracy and epochs. After 14 epochs, the accuracy reached more than 85% in both the train and test set.</p> Full article ">
9 pages, 3054 KiB  
Brief Report
The Histology-Driven Differential Diagnosis in Bowel Inflammatory Conditions Is Not All That Obvious: Evidence from a Survey Based on Digital Slides
by Gabriella Canavese, Enrico Costantino Falco, Nuria Perez-Diaz-del-Campo, Gian Paolo Caviglia, Fabrizia Di Giovanni and Davide Giuseppe Ribaldone
Diagnostics 2023, 13(24), 3684; https://doi.org/10.3390/diagnostics13243684 - 18 Dec 2023
Viewed by 1516
Abstract
(1) Background: when the pathologist faces histologic slides from colonoscopies in daily practice, given the large number of entities and etiologies under inflammatory bowel conditions, in-depth definition of the histological spectrum and the recommendations of current guidelines are often not enough to conclusively [...] Read more.
(1) Background: when the pathologist faces histologic slides from colonoscopies in daily practice, given the large number of entities and etiologies under inflammatory bowel conditions, in-depth definition of the histological spectrum and the recommendations of current guidelines are often not enough to conclusively define a diagnostic framework. Histological patterns should be organized hierarchically in flowcharts that consider the correlation with clinical data. We conducted an online survey asking a group of gastroenteropathologists to apply a pattern classification based on the most significant lesions in colitis differential diagnosis: crypt distortion and activity. (2) Methods: digital slides from 20 endoscopy samples were analyzed by twenty pathologists and classified according to the occurrence of crypt distortion (nondestructive–destructive colitis) and subsequently to the evidence of activity (ND1-2-3, D1-2). (3) Results: in 8 out of 20 (40%) cases, the participants reached a full agreement regarding the evaluation of crypt distortion (5 cases: nondestructive colitis; 3 cases: destructive colitis). The calculated agreement was k = 0.432. In the second-level quiz (ND1-2-3 and D1-2), full agreement between participants was achieved for 7 of the 28 (25%) possible classifications, with k = 0.229. (4) Conclusions: The findings from this survey are indicative of an unexpectedly low consensus, even among dedicated pathologists, about the recognition of histological changes that are commonly considered critical lesions in the histologic identification of bowel non-neoplastic diseases. In our opinion, these divergences imply a significant risk of misdiagnosis of bowel inflammatory conditions, hampering the usefulness of histological assessment. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Classification scheme of colitis pattern (From Carpenter et al. [<a href="#B13-diagnostics-13-03684" class="html-bibr">13</a>], modif.).</p> Full article ">Figure 2
<p>Graphic schemes of pattern classification adopted in the survey.</p> Full article ">Figure 2 Cont.
<p>Graphic schemes of pattern classification adopted in the survey.</p> Full article ">Figure 3
<p>Case 9 Image of a sample from rectum (O.M.: 40×, <b>left</b>): Crypt anomalies in frames A and B (O.M.: 200×, <b>right</b>) were interpreted as true crypt distortion, and the inflammation was classified as crypt destructive colitis by 60% of the participants. Activity evaluation in this group was controversial (1/3 present, 1/3 absent, 1/3 unclassifiable). Rate of classifications in diagram.</p> Full article ">Figure 4
<p>Case 5 Image of a sample from right colon (O.M.: 100×, <b>upper left</b>): Crypt anomalies in frame B were interpreted as artefactual, and the inflammation was classified as crypt nondestructive colitis by 80% of the participants and was defined by 50% of the participants as ND3 colitis, with an increase in intraepithelial lymphocytes (Frame A—O.M.: 200×, <b>lower left</b>). Rate of classifications in diagram.</p> Full article ">
12 pages, 2780 KiB  
Article
ECMO in Myocardial Infarction-Associated Cardiogenic Shock: Blood Biomarkers as Predictors of Mortality
by Thomas Senoner, Benedikt Treml, Robert Breitkopf, Ulvi Cenk Oezpeker, Nicole Innerhofer, Christine Eckhardt, Aleksandra Radovanovic Spurnic and Sasa Rajsic
Diagnostics 2023, 13(24), 3683; https://doi.org/10.3390/diagnostics13243683 - 17 Dec 2023
Cited by 2 | Viewed by 1159
Abstract
Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) can provide circulatory and respiratory support in patients with cardiogenic shock. The main aim of this work was to investigate the association of blood biomarkers with mortality in patients with myocardial infarction needing va-ECMO support. Methods: We [...] Read more.
Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) can provide circulatory and respiratory support in patients with cardiogenic shock. The main aim of this work was to investigate the association of blood biomarkers with mortality in patients with myocardial infarction needing va-ECMO support. Methods: We retrospectively analyzed electronic medical charts from patients receiving va-ECMO support in the period from 2008 to 2021 at the Medical University Innsbruck, Department of Anesthesiology and Intensive Care Medicine. Results: Of 188 patients, 57% (108/188) survived to discharge, with hemorrhage (46%) and thrombosis (27%) as the most frequent adverse events. Procalcitonin levels were markedly higher in non-survivors compared with survivors during the observation period. The multivariable model identified higher blood levels of procalcitonin (HR 1.01, p = 0.002) as a laboratory parameter associated with a higher risk of mortality. Conclusions: In our study population of patients with myocardial infarction-associated cardiogenic shock, deceased patients had increased levels of inflammatory blood biomarkers throughout the whole study period. Increased procalcitonin levels have been associated with a higher risk of mortality. Future studies are needed to show the role of procalcitonin in patients receiving ECMO support. Full article
(This article belongs to the Special Issue Diagnostics in Critical Care)
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<p>C-reactive protein trend throughout support (mean values). ECMO, extracorporeal membrane oxygenation. Data are presented as mean.</p> Full article ">Figure 2
<p>Procalcitonin trend throughout support (mean values). ECMO, extracorporeal membrane oxygenation. Data are presented as mean.</p> Full article ">Figure 3
<p>Fibrinogen trend throughout support (mean values). ECMO, extracorporeal membrane oxygenation. Data are presented as mean.</p> Full article ">Figure 4
<p>Platelets count trend throughout support (mean values). ECMO: extracorporeal membrane oxygenation. Data are presented as mean.</p> Full article ">
13 pages, 3340 KiB  
Systematic Review
Clinical Validity of Anti-Proteinase 3 Antibodies in Patients with Inflammatory Bowel Disease: A Short Meta-Analysis
by Carmen Andalucía, Laura Martínez-Prat, Chelsea Bentow, Mary Ann Aure, Michael P. Horn and Michael Mahler
Diagnostics 2023, 13(24), 3682; https://doi.org/10.3390/diagnostics13243682 - 16 Dec 2023
Cited by 3 | Viewed by 2006
Abstract
Anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3 (PR3) represent highly established markers for patients with ANCA-associated vasculitis (AAV). PR3-ANCA have also demonstrated utility in the management of inflammatory bowel disease (IBD). More specifically, PR3-ANCA discriminate individuals with ulcerative colitis (UC) from Crohn’s [...] Read more.
Anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3 (PR3) represent highly established markers for patients with ANCA-associated vasculitis (AAV). PR3-ANCA have also demonstrated utility in the management of inflammatory bowel disease (IBD). More specifically, PR3-ANCA discriminate individuals with ulcerative colitis (UC) from Crohn’s disease (CD) patients and are associated with disease severity, activity, and treatment non-response. Here, we aim to summarize the current data on the diagnostic utility of PR3-ANCA in IBD. A structured, systematic literature review, including three electronic databases, was conducted on June 6th, 2023, to identify studies assessing the diagnostic accuracy of the QUANTA Flash® PR3 assay in UC vs. CD patients. Electronic searches were supplemented by hand searching. A hierarchical, bivariate, mixed-effect meta-analysis was conducted using the metandi function, as per the Cochrane collaboration recommendations. Study quality was assessed using the QUADAS-2 tool, which considers the risk of bias and applicability. Six out of a hundred and eleven citations met the inclusion criteria and reported QUANTA Flash® PR3 diagnostic accuracy in UC vs. CD (UC, n = 667, CD, n = 682 patients). The sensitivity/specificity point estimate for UC was 34.9%/95.9%. This resulted in a Diagnostic Odds Ratio (DOR) of 12.6. The risk of bias was low in the index test and reference standard domains. Four of the six studies (67%) showed an unclear risk of bias in patient selection and in flow and timing domains. All studies had low concerns about applicability in all the domains. PR3-ANCA measured with the QUANTA Flash® PR3 assay represent novel diagnostic markers in IBD and enables discrimination between UC and CD. Full article
(This article belongs to the Special Issue Diagnostic Procedures for Inflammatory Bowel Disease: Laboratory, Endoscopy, Pathology, Imaging and Beyond)
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Figure 1
<p>PRISMA 2020 flow diagram for new systematic reviews, which includes searches of databases, registers, and other sources.</p> Full article ">Figure 2
<p>Forest plot of sensitivity and specificity of the PR3-ANCA for detection of ulcerative colitis (UC) and Crohn’s disease (CD). The vertical red dotted line represents the meta-analysis summary estimate, which corresponds to the value of 0.35 for sensitivity and 0.96 for specificity. A total of six studies are shown individually and combined for sensitivity and specificity. The combined sensitivity and specificity were 34.9% and 95.9%, respectively [<a href="#B7-diagnostics-13-03682" class="html-bibr">7</a>,<a href="#B8-diagnostics-13-03682" class="html-bibr">8</a>,<a href="#B9-diagnostics-13-03682" class="html-bibr">9</a>,<a href="#B12-diagnostics-13-03682" class="html-bibr">12</a>,<a href="#B13-diagnostics-13-03682" class="html-bibr">13</a>,<a href="#B14-diagnostics-13-03682" class="html-bibr">14</a>].</p> Full article ">Figure 3
<p>Summary receiver operating characteristic plot of PR3-ANA to discriminate between ulcerative colitis (UC) and Crohn’s disease (CD). The size of each point is scaled according to the precision, sensitivity, and specificity of the study [<a href="#B7-diagnostics-13-03682" class="html-bibr">7</a>,<a href="#B8-diagnostics-13-03682" class="html-bibr">8</a>,<a href="#B9-diagnostics-13-03682" class="html-bibr">9</a>,<a href="#B12-diagnostics-13-03682" class="html-bibr">12</a>,<a href="#B13-diagnostics-13-03682" class="html-bibr">13</a>,<a href="#B14-diagnostics-13-03682" class="html-bibr">14</a>]. The solid circle (summary point) represents the summary estimate of sensitivity and specificity for PR3-ANCA. The summary point is surrounded by a dotted line representing the 95% confidence region and a dashed line representing the 95% prediction region (the region within which we are 95% certain that the results of a new study will lie).</p> Full article ">Figure 4
<p>Impact of the PR3-ANCA test result on the probability of ulcerative colitis (UC). (<b>A</b>) Fagan´s nomogram for the QUANTA Flash<sup>®</sup> PR3 assay. For example, the QUANTA Flash PR3 assay in high-risk patients has an estimated diagnostic sensitivity (DSe) of 34.9% and specificity (DSp) of 95.9% for ulcerative colitis (UC). It is necessary to calculate first the likelihood ratio of positive and negative test results separately (LR+ and LR−, respectively) using conventional formulas (LR+ =  DSe/(1 − DSp) and LR−  =  (1 − DSe)/DSp). Given that the patient came from a high-risk population with an estimated prevalence of 25%, if this patient tests positive, the post-test probability that this person truly has UC would be approximately % (red line). Alternatively, if the patient tests negative, the post-test probability that the patient truly has UC would be approximately 18% (green line). (<b>B</b>) Pre-test/post-test probability plots.</p> Full article ">Figure 5
<p>Summary of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2): evaluating the risk of bias and applicability concerns. It consists of four domains (patient selection, index test, reference standard, flow, and timing). All domains are rated as “low”, “high”, or “unclear” in relation to the risk of bias, and the first three domains in regard to applicability concerns.</p> Full article ">
13 pages, 2157 KiB  
Article
Prehospital Targeting of 1-Year Mortality in Acute Chest Pain by Cardiac Biomarkers
by Daniel Zalama-Sánchez, Francisco Martín-Rodríguez, Raúl López-Izquierdo, Juan F. Delgado Benito, Irene Sánchez Soberón, Carlos del Pozo Vegas and Ancor Sanz-García
Diagnostics 2023, 13(24), 3681; https://doi.org/10.3390/diagnostics13243681 - 16 Dec 2023
Viewed by 980
Abstract
The identification and appropriate management of patients at risk of suffering from acute chest pain (ACP) in prehospital care are not straightforward. This task could benefit, as occurs in emergency departments (EDs), from cardiac enzyme assessment. The aim of the present work was [...] Read more.
The identification and appropriate management of patients at risk of suffering from acute chest pain (ACP) in prehospital care are not straightforward. This task could benefit, as occurs in emergency departments (EDs), from cardiac enzyme assessment. The aim of the present work was to derive and validate a scoring system based on troponin T (cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), and D-dimer to predict 1-year mortality in patients with ACP. This was a prospective, multicenter, ambulance-based cohort study of adult patients with a prehospital ACP diagnosis who were evacuated by ambulance to the ED between October 2019 and July 2021. The primary outcome was 365-day cumulative mortality. A total of 496 patients fulfilled the inclusion criteria. The mortality rate was 12.1% (60 patients). The scores derived from cTnT, NT-proBNP, and D-dimer presented an AUC of 0.802 (95% CI: 0718-0.886) for 365-day mortality. This AUC was superior to that of each individual cardiac enzyme. Our study provides promising evidence for the predictive value of a risk score based on cTnT, NT-proBNP, and D-dimer for the prediction of 1-year mortality in patients with ACP. The implementation of this score has the potential to benefit emergency medical service care and facilitate the on-scene decision-making process. Full article
(This article belongs to the Special Issue Novel Methods and Devices for Monitoring in Critical Care)
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<p>Flowchart of the study population.</p> Full article ">Figure 2
<p>Score predictive validity for 1-year mortality. (<b>a</b>) Observed distribution of the outcome based on the score. The solid line shows the predicted probability of the outcome; the gray shadowed area shows the 95% confidence interval. (<b>b</b>) AUC for 1-year mortality in the validation cohort.</p> Full article ">Figure 3
<p>AUCs for 1-year mortality in the validation cohort according to different subsets. (<b>a</b>) ACP, (<b>b</b>) MIC, (<b>c</b>) female, (<b>d</b>) male, (<b>e</b>) 18 to 49 years, (<b>f</b>) 50 to 74 years, (<b>g</b>) over 74 years. Abbreviations: AUC—area under the curve of the receiver operating characteristic; CI—confidence interval.</p> Full article ">Figure 4
<p>AUC for 1-year mortality in the validation cohort according to the different parameters included in the score considered individually. (<b>a</b>) cTnT, (<b>b</b>) NT-proBNP, and (<b>c</b>) D-dimer. All the tables had <span class="html-italic">p</span> values &lt; 0.05, except for (<b>c</b>). Abbreviations: AUC—area under the curve of the receiver operating characteristic; CI—confidence interval.</p> Full article ">
18 pages, 317 KiB  
Review
Evolution of Systemic Therapy in Medulloblastoma Including Irradiation-Sparing Approaches
by Naureen Mushtaq, Rahat Ul Ain, Syed Ahmer Hamid and Eric Bouffet
Diagnostics 2023, 13(24), 3680; https://doi.org/10.3390/diagnostics13243680 - 16 Dec 2023
Cited by 2 | Viewed by 1993
Abstract
The management of medulloblastoma in children has dramatically changed over the past four decades, with the development of chemotherapy protocols aiming at improving survival and reducing long-term toxicities of high-dose craniospinal radiotherapy. While the staging and treatment of medulloblastoma were until recently based [...] Read more.
The management of medulloblastoma in children has dramatically changed over the past four decades, with the development of chemotherapy protocols aiming at improving survival and reducing long-term toxicities of high-dose craniospinal radiotherapy. While the staging and treatment of medulloblastoma were until recently based on the modified Chang’s system, recent advances in the molecular biology of medulloblastoma have revolutionized approaches in the management of this increasingly complex disease. The evolution of systemic therapies is described in this review. Full article
(This article belongs to the Special Issue Medulloblastoma—Existing and Evolving Landscape)
13 pages, 1917 KiB  
Article
Whole Brain and Corpus Callosum Fractional Anisotropy Differences in Patients with Cognitive Impairment
by Kalvis Kaļva, Nauris Zdanovskis, Kristīne Šneidere, Andrejs Kostiks, Guntis Karelis, Ardis Platkājis and Ainārs Stepens
Diagnostics 2023, 13(24), 3679; https://doi.org/10.3390/diagnostics13243679 - 16 Dec 2023
Viewed by 2231
Abstract
Diffusion tensor imaging (DTI) is an MRI analysis method that could help assess cognitive impairment (CI) in the ageing population more accurately. In this research, we evaluated fractional anisotropy (FA) of whole brain (WB) and corpus callosum (CC) in patients with normal cognition [...] Read more.
Diffusion tensor imaging (DTI) is an MRI analysis method that could help assess cognitive impairment (CI) in the ageing population more accurately. In this research, we evaluated fractional anisotropy (FA) of whole brain (WB) and corpus callosum (CC) in patients with normal cognition (NC), mild cognitive impairment (MCI), and moderate/severe cognitive impairment (SCI). In total, 41 participants were included in a cross-sectional study and divided into groups based on Montreal Cognitive Assessment (MoCA) scores (NC group, nine participants, MCI group, sixteen participants, and SCI group, sixteen participants). All participants underwent an MRI examination that included a DTI sequence. FA values between the groups were assessed by analysing FA value and age normative percentile. We did not find statistically significant differences between the groups when analysing CC FA values. Both approaches showed statistically significant differences in WB FA values between the MCI-SCI and MCI-NC groups, where the MCI group participants showed the highest mean FA and highest mean FA normative percentile results in WB. Full article
(This article belongs to the Special Issue Neuropathology, Neuroimaging and Biomarkers in Neurological Disease)
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<p>DTI examination with colour-coded fibre pathways in axial, sagittal, and coronal planes.</p> Full article ">Figure 2
<p>WB FA value comparisons between (from left to right) SCI, MCI, and NC with data distribution in each group.</p> Full article ">Figure 3
<p>WB FA normative percentile comparisons between (from left to right) SCI, MCI, and NC with data distribution in each group.</p> Full article ">Figure 4
<p>CC FA comparisons between (from left to right) SCI, MCI, and NC with data distribution in each group.</p> Full article ">Figure 5
<p>CC FA normative percentile comparisons between (from left to right) SCI, MCI, and NC with data distribution in each group.</p> Full article ">
12 pages, 562 KiB  
Article
Development of Quality Indicators for the Ultrasound Department through a Modified Delphi Method
by Aiping Zeng, Yang Gu, Li Ma, Xixi Tao, Luying Gao, Jianchu Li, Hongyan Wang and Yuxin Jiang
Diagnostics 2023, 13(24), 3678; https://doi.org/10.3390/diagnostics13243678 - 15 Dec 2023
Cited by 1 | Viewed by 1260
Abstract
This study aims to establish precise quality indicators for evaluating and enhancing ultrasound performance, employing a methodology based on a comprehensive review of the literature, expert insights, and practical application experiences. We conducted a thorough review of both the domestic and international literature [...] Read more.
This study aims to establish precise quality indicators for evaluating and enhancing ultrasound performance, employing a methodology based on a comprehensive review of the literature, expert insights, and practical application experiences. We conducted a thorough review of both the domestic and international literature on ultrasound quality control to identify potential indicators. A dedicated team was formed to oversee the complete indicator development process. Utilizing a three-round modified Delphi method, we sought expert opinions through personalized email correspondence. Subsequently, data from diverse hospital indicators were collected to validate and assess feasibility. A novel set of seven indicators was compiled initially, followed by the convening of a 36-member nationally representative expert panel. After three rounds of meticulous revisions, consensus was reached on 13 indicators across three domains. These finalized indicators underwent application in various hospital settings, demonstrating their initial validity and feasibility. The development of thirteen ultrasound quality indicators represents a significant milestone in evaluating ultrasound performance. These indicators empower hospitals to monitor changes in quality effectively, fostering efficient quality management practices. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>Stages in the development of ultrasound quality indicators.</p> Full article ">
22 pages, 3367 KiB  
Systematic Review
Artificial Intelligence and Its Clinical Applications in Orthodontics: A Systematic Review
by Gianna Dipalma, Alessio Danilo Inchingolo, Angelo Michele Inchingolo, Fabio Piras, Vincenzo Carpentiere, Grazia Garofoli, Daniela Azzollini, Merigrazia Campanelli, Gregorio Paduanelli, Andrea Palermo and Francesco Inchingolo
Diagnostics 2023, 13(24), 3677; https://doi.org/10.3390/diagnostics13243677 - 15 Dec 2023
Cited by 6 | Viewed by 2618
Abstract
This review aims to analyze different strategies that make use of artificial intelligence to enhance diagnosis, treatment planning, and monitoring in orthodontics. Orthodontics has seen significant technological advancements with the introduction of digital equipment, including cone beam computed tomography, intraoral scanners, and software [...] Read more.
This review aims to analyze different strategies that make use of artificial intelligence to enhance diagnosis, treatment planning, and monitoring in orthodontics. Orthodontics has seen significant technological advancements with the introduction of digital equipment, including cone beam computed tomography, intraoral scanners, and software coupled to these devices. The use of deep learning in software has sped up image processing processes. Deep learning is an artificial intelligence technology that trains computers to analyze data like the human brain does. Deep learning models are capable of recognizing complex patterns in photos, text, audio, and other data to generate accurate information and predictions. Materials and Methods: Pubmed, Scopus, and Web of Science were used to discover publications from 1 January 2013 to 18 October 2023 that matched our topic. A comparison of various artificial intelligence applications in orthodontics was generated. Results: A final number of 33 studies were included in the review for qualitative analysis. Conclusions: These studies demonstrate the effectiveness of AI in enhancing orthodontic diagnosis, treatment planning, and assessment. A lot of articles emphasize the integration of artificial intelligence into orthodontics and its potential to revolutionize treatment monitoring, evaluation, and patient outcomes. Full article
(This article belongs to the Special Issue Artificial Intelligence in Dental Medicine)
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<p>Example of the identification of cephalometric points by AI from a lateral–lateral teleradiographic image required for orthodontic purposes.</p> Full article ">Figure 2
<p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart of the literature search and article inclusion process.</p> Full article ">Figure 3
<p>Quality assessment of bias [<a href="#B5-diagnostics-13-03677" class="html-bibr">5</a>,<a href="#B31-diagnostics-13-03677" class="html-bibr">31</a>,<a href="#B32-diagnostics-13-03677" class="html-bibr">32</a>,<a href="#B33-diagnostics-13-03677" class="html-bibr">33</a>,<a href="#B34-diagnostics-13-03677" class="html-bibr">34</a>,<a href="#B35-diagnostics-13-03677" class="html-bibr">35</a>,<a href="#B37-diagnostics-13-03677" class="html-bibr">37</a>,<a href="#B38-diagnostics-13-03677" class="html-bibr">38</a>,<a href="#B39-diagnostics-13-03677" class="html-bibr">39</a>,<a href="#B40-diagnostics-13-03677" class="html-bibr">40</a>,<a href="#B41-diagnostics-13-03677" class="html-bibr">41</a>,<a href="#B42-diagnostics-13-03677" class="html-bibr">42</a>,<a href="#B43-diagnostics-13-03677" class="html-bibr">43</a>,<a href="#B44-diagnostics-13-03677" class="html-bibr">44</a>,<a href="#B46-diagnostics-13-03677" class="html-bibr">46</a>,<a href="#B47-diagnostics-13-03677" class="html-bibr">47</a>,<a href="#B49-diagnostics-13-03677" class="html-bibr">49</a>,<a href="#B51-diagnostics-13-03677" class="html-bibr">51</a>,<a href="#B53-diagnostics-13-03677" class="html-bibr">53</a>,<a href="#B54-diagnostics-13-03677" class="html-bibr">54</a>,<a href="#B59-diagnostics-13-03677" class="html-bibr">59</a>,<a href="#B62-diagnostics-13-03677" class="html-bibr">62</a>,<a href="#B63-diagnostics-13-03677" class="html-bibr">63</a>,<a href="#B64-diagnostics-13-03677" class="html-bibr">64</a>,<a href="#B65-diagnostics-13-03677" class="html-bibr">65</a>,<a href="#B66-diagnostics-13-03677" class="html-bibr">66</a>,<a href="#B67-diagnostics-13-03677" class="html-bibr">67</a>,<a href="#B68-diagnostics-13-03677" class="html-bibr">68</a>,<a href="#B70-diagnostics-13-03677" class="html-bibr">70</a>,<a href="#B72-diagnostics-13-03677" class="html-bibr">72</a>].</p> Full article ">
4 pages, 1818 KiB  
Interesting Images
Immunohistochemistry in an Adult Case of Bitot’s Spots Caused by Vitamin A Deficiency
by Hideki Fukuoka, Norihiko Yokoi and Chie Sotozono
Diagnostics 2023, 13(24), 3676; https://doi.org/10.3390/diagnostics13243676 - 15 Dec 2023
Viewed by 1462
Abstract
Bitot’s spots (BS) are the buildup of superficially located keratin in the conjunctiva and are early indicators of vitamin A deficiency (VAD), primarily due to malnutrition and malabsorption, thus leading to xerophthalmia. BS are particularly prevalent in developing countries, and their presence necessitates [...] Read more.
Bitot’s spots (BS) are the buildup of superficially located keratin in the conjunctiva and are early indicators of vitamin A deficiency (VAD), primarily due to malnutrition and malabsorption, thus leading to xerophthalmia. BS are particularly prevalent in developing countries, and their presence necessitates prompt vitamin A supplementation to avert blindness, with the immunohistochemical characteristics of BS aiding in understanding the extent of epithelial abnormalities and the efficacy of vitamin A supplementation. We describe the case of a 34-year-old male with persistent BS despite extensive vitamin A supplementation and topical treatments who underwent surgical excision of the BS followed by amniotic membrane transplantation, thus resulting in symptom relief and epithelialization, with no recurrence observed during follow-up. Histopathologic and immunohistochemical evaluations revealed expression of keratinization-related proteins, along with an absence of mucin-5AC-positive cells, suggesting impaired differentiation into goblet cells due to VAD. This case highlights the potential age-related disparity in the efficacy of vitamin A supplementation, emphasizing the need for early detection and a multidisciplinary approach in the management of VAD, especially in young adults. The favorable outcome of surgical intervention highlights its viability in the management of persistent BS and encourages further investigation to optimize therapeutic strategies for VAD-related ocular manifestations. Full article
(This article belongs to the Special Issue Diagnosis, Treatment and Management of Eye Diseases)
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<p>A 34-year-old east Asian (Japanese) male with bilateral ocular dryness and foreign body sensation was ultimately referred to our hospital for further evaluation after a 1-year treatment with a P2Y2 receptor agonist (diquafosol), rebamipide, and betamethasone eye drops for allergic conjunctivitis and dry eye at an outside clinic was unsuccessful for relieving the symptoms. Upon initial examination, his bilateral best-corrected visual acuity was better than 20/20; however, Bitot’s spots (BS) were observed on the nasal and temporal conjunctiva in both eyes (<b>A-1</b>,<b>A-2</b>). Laboratory tests revealed a serum vitamin A level of 80 IU/dL (normal range: 97–316 IU/dL), thus confirming vitamin A deficiency, and investigation into the patient's dietary history revealed a significant lack of vegetable consumption due to the coronavirus disease 2019 (COVID-19) pandemic lockdown. For treatment, the patient was administered 30,000 IU of vitamin A along with rebamipide eye drops four times daily, levofloxacin eye drops, and low-dose steroid eye drops twice daily. At the 4-month follow-up visit, there was no improvement in BS despite the serum vitamin A level having increased to 120 IU/dL. Subsequently, surgical excision of the BS followed by amniotic membrane transplantation was performed. Post-surgery, epithelialization occurred, the patient's symptoms subsided, and no recurrence of the BS was observed throughout the subsequent follow-up period. Preoperative impression cytology of the conjunctiva including BS and excision specimens were subjected to histopathologic and immunohistochemical evaluation. In the preoperative impression cytology of the area of the BS, it was not possible to obtain tissue directly from the BS, and only tissue from other areas could be obtained. Slit-lamp microscopy images of the patient's right (left-side column) and left (right-side column) eyes showed elevated BS stained with Lissamine Green before (top row) and after (bottom row) surgical excision of the BS and amniotic membrane transplantation. Preoperative images showing Lissamine Green staining revealed elevated BS located nasally and temporally in both eyes, with the temporal lesions being larger than the nasal ones (<b>A-1</b>,<b>A-2</b>). Postoperative images showed complete resolution of the BS (<b>B-1,B-2</b>).</p> Full article ">Figure 2
<p>Hematoxylin and eosin-stained pathological tissue specimen of an excised Bitot’s spots (BS) showing squamous metaplasia and keratinization in the superficial layers. The type of keratinization observed is hyperkeratosis, as evidenced by the retention of nuclei in the keratinized cells. (<b>A</b>) Scale Bar = 50 μm. Pathology showed squamous epithelialization and parakeratosis of the superficial epithelium (<a href="#diagnostics-13-03676-f002" class="html-fig">Figure 2</a>). Images showing immunofluorescent results against cytokeratins, keratinization, and mucin (MUC) markers of the obtained tissue (<b>B</b>–<b>I</b>). (<b>B</b>) Cytokeratin (CK) 1, (<b>C</b>) CK10, (<b>D</b>) CK4, (<b>E</b>) CK13, (<b>F</b>) transglutaminase-1, (<b>G</b>) filaggrin, (<b>H</b>) involucrin, and (<b>I</b>) MUC5AC (green) and DAPI for counter-staining (blue) for the BS. Bar = 50 μm. BS tissues were collected during surgery and embedded in Tissue-Tek<sup>®</sup> O.C.T. Compound (Sakura Finetek USA, Inc., Torrance, CA, USA), then snap-frozen in liquid nitrogen. Next, 8 μm thick frozen sections were prepared on slides, air-dried, and fixed in Zamboni’s fixative, and then washed in 0.01M phosphate-buffered saline. The sections were then blocked with 1% bovine serum albumin before incubating overnight at 4°C with primary antibodies, followed by Alexa Fluor 488 conjugated secondary antibodies and once again being washed. Finally, the sections were imaged using a fluorescence microscope. In the conjunctival impression cytology, it was not possible to directly retrieve epithelial cells covering the BS, which were negative for mucin-5AC (MUC5AC). Immunohistochemical analysis showed that BS pathological tissue expressed CK1, CK4, CK13, and keratinization-related proteins (i.e., transglutaminase 1 and filaggrin) (white arrow heads) and was negative for CK10, loricrin, and MUC5AC (<a href="#diagnostics-13-03676-f002" class="html-fig">Figure 2</a>). BS are characteristic lesions of the buildup of superficially located keratin in the conjunctiva and are early indicators of vitamin A deficiency (VAD) [<a href="#B1-diagnostics-13-03676" class="html-bibr">1</a>], a condition that can lead to blindness as vitamin A is critical for normal differentiation and proliferation of human conjunctival epithelium. The primary underlying cause of VAD is malnutrition, followed by malabsorption, which can lead to a variety of ocular manifestations collectively known as xerophthalmia. BS are specific early signs of VAD and present as dry, whitish, foamy, oval, triangular, or irregular-shaped lesions on the conjunctiva, primarily on the temporal side of the eye, and they consist mainly of keratin mixed with the gas-forming bacteria Corynebacterium xerosis, which gives them their foamy appearance [<a href="#B2-diagnostics-13-03676" class="html-bibr">2</a>]. In eyes afflicted with BS, early intervention with vitamin A supplements can reverse the condition and stop the progression to blindness. However, if left untreated and xerophthalmia and blindness develop, mortality rates can be as high as 40% within the first year of diagnosis [<a href="#B3-diagnostics-13-03676" class="html-bibr">3</a>]. In addition, the prevalence of BS in children is often used to assess the burden of vitamin A deficiency, particularly in developing countries where malnutrition is prevalent [<a href="#B4-diagnostics-13-03676" class="html-bibr">4</a>]. Vitamin A is critical for cell differentiation and affects genome expression by regulating certain gene transcriptions, modifying mRNA levels, and altering membrane structure and function. Moreover, it affects protein biosynthesis, including proteins essential for development and cell function, and influences the formation of hormone-like secretory proteins. VAD disrupts these processes and leads to differentiation disorders and conditions such as BS [<a href="#B2-diagnostics-13-03676" class="html-bibr">2</a>]. The case presented in this report highlights the persistence and severity of VAD, particularly in young adults, and the resulting therapeutic challenges. In contrast to younger individuals in whom vitamin A supplementation [<a href="#B3-diagnostics-13-03676" class="html-bibr">3</a>,<a href="#B5-diagnostics-13-03676" class="html-bibr">5</a>] often results in a rapid resolution of the symptoms, our patient, a 34-year-old male, had a more refractory course. Despite extensive vitamin A supplementation along with topical treatments, the BS—a hallmark of VAD—remained refractory, highlighting a potential age-related disparity in therapeutic outcomes. We believe that prolonged vitamin A deficiency remains the most likely primary cause underlying the persistent BS in this case. Even with supplementation, the turnover and replacement of his markedly affected conjunctival tissue are both difficult and slow. Therefore, we suspect that refractory BS have persisted due to the severity and duration of his long-standing deficiency rather than genetics or other factors. Although surgical excision of the BS followed by amniotic membrane transplantation proved to be a highly effective solution, there are currently no published reports on the efficacy of amniotic membrane transplantation for BS. In the present case, postoperative epithelialization occurred, leading to a significant improvement in the symptoms, thus highlighting the potential role of surgery as a viable option in the management of persistent BS in young adults. In addition, the histopathologic and immunohistochemical evaluations provided valuable insights into the pathology of BS. The presence of CK4 and CK13 derived from mucosal tissues emphasizes that the epithelium retains mucosal properties [<a href="#B6-diagnostics-13-03676" class="html-bibr">6</a>]. Interestingly, the detection of CK1, a protein typically expressed in skin tissues [<a href="#B7-diagnostics-13-03676" class="html-bibr">7</a>], and the keratinization-related proteins transglutaminase-1 and filaggrin highlight a remarkable degree of keratinization. The absence of involucrin [<a href="#B8-diagnostics-13-03676" class="html-bibr">8</a>] further delineates the state of partial keratinization, characteristic of defective keratinization such as parakeratosis, possibly driven by VAD [<a href="#B9-diagnostics-13-03676" class="html-bibr">9</a>]. The absence of MUC5AC-positive cells in preoperative conjunctival impression cytology, including BS and excised specimens, suggests that VAD may impair differentiation into goblet cells [<a href="#B10-diagnostics-13-03676" class="html-bibr">10</a>,<a href="#B11-diagnostics-13-03676" class="html-bibr">11</a>,<a href="#B12-diagnostics-13-03676" class="html-bibr">12</a>]. In the published literature, there is evidence that retinoid signaling regulates goblet cell differentiation in the eye, including the findings in the recent report by Alam et al. that showed decreased conjunctival goblet cells in vitamin A deficiency and attenuated goblet cell numbers with disrupted RXRα signaling [<a href="#B13-diagnostics-13-03676" class="html-bibr">13</a>]. Those findings demonstrate that retinoid signals play an indispensable role in ocular surface goblet cell homeostasis. The case presented in this report highlights the critical role of early detection and multidisciplinary management in mitigating the sequelae of VAD. The differential response to vitamin A supplementation between younger individuals and young adults requires further investigation to elucidate the underlying mechanisms and optimize therapeutic strategies. It should be noted that the findings in this report are consistent with the existing literature describing the interplay between vitamin A, epithelial integrity, and ocular surface disorders, including dry eye and superior limbic keratoconjunctivitis. The nuanced understanding of the pathological changes and the efficacy of surgical intervention in this present case contribute to the broader discourse on the management of ocular manifestations of VAD. The present case highlights the complexity of treating VAD in young adults and demonstrates a potential age-related disparity in outcomes. Surgical intervention with excision of BS and amniotic membrane transplantation proved effective in alleviating symptoms, highlighting the need for a multidisciplinary approach and further investigation to optimize therapeutic strategies. In regard to the immunohistochemistry of BS, further research is required, as the scientific information has yet to be elucidated in detail, i.e., the cellular and molecular aspects of BS and their interaction with vitamin A at the tissue level would provide a deeper understanding of the pathology and mechanisms underlying this condition. In addition, further investigation into the immunohistochemical characteristics of BS may shed light on the extent of epithelial abnormalities and the efficacy of vitamin A supplementation in reversing those abnormalities.</p> Full article ">
13 pages, 1008 KiB  
Article
Variety of Serotonin Levels in Pediatric Gastrointestinal Disorders
by Loredana Matiș, Lucia Georgeta Daina, Lavinia Maris, Timea Claudia Ghitea, Daniela Florina Trifan, Ioana Moga and Radu Fodor
Diagnostics 2023, 13(24), 3675; https://doi.org/10.3390/diagnostics13243675 - 15 Dec 2023
Cited by 1 | Viewed by 1351
Abstract
(1) Serotonin primarily regulates our emotions. A complex process, which includes dysfunctions in gastrointestinal motility and deregulation of the gene responsible for serotonin reuptake (SERT), is implicated in the pathophysiology of irritable bowel syndrome (IBS). This also encompasses changes in intestinal microbiota, the [...] Read more.
(1) Serotonin primarily regulates our emotions. A complex process, which includes dysfunctions in gastrointestinal motility and deregulation of the gene responsible for serotonin reuptake (SERT), is implicated in the pathophysiology of irritable bowel syndrome (IBS). This also encompasses changes in intestinal microbiota, the response to stress, the intricate interplay between the brain and the digestive tract, heightened sensitivity to visceral stimuli, and low-grade inflammation. This paper aims to investigate the effectiveness of probiotic therapy in managing gastrointestinal and neuropsychiatric symptoms related to serotonin levels, with a focus on individuals with serotonin deficiency and those with normal serotonin levels experiencing gastrointestinal disorders. (2) The study involved 135 pediatric patients aged 5–18 years with gastrointestinal disturbances, including constipation, diarrhea, and other symptoms, such as nausea, flatulence, feeling full, or gastrointestinal pain. (3) Serotonin testing was performed, and administering probiotics appeared to be effective in addressing serotonin deficiency and other gastrointestinal disorders. (4) Serotonin’s pivotal role in regulating neurotransmitter secretion and its impact on neuropsychiatric health, coupled with gender differences and age-related declines, underscore the complexity of their influence on gastrointestinal and neuropsychiatric conditions. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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Graphical abstract
Full article ">Figure 1
<p>Demographic distribution of patients based on serotonin-level assessment in case of study groups (<b>A</b>), gender (<b>B</b>), age (<b>C</b>), environment of origin (<b>D</b>), where ‘*’ represents only one exceptional case, and ‘°’ represents more isolated cases.</p> Full article ">Figure 1 Cont.
<p>Demographic distribution of patients based on serotonin-level assessment in case of study groups (<b>A</b>), gender (<b>B</b>), age (<b>C</b>), environment of origin (<b>D</b>), where ‘*’ represents only one exceptional case, and ‘°’ represents more isolated cases.</p> Full article ">Figure 2
<p>Differences in the progression of gastrointestinal symptoms based on serotonin levels.</p> Full article ">Figure 3
<p>Graphical presentation of the correlations between serotonin levels and the progression of gastrointestinal symptoms, as constipation (<b>A</b>), diarrhea (<b>B</b>), and gastrointestinal problems (<b>C</b>).</p> Full article ">
11 pages, 1199 KiB  
Article
Cardiac Involvement in Classical Organic Acidurias: Clinical Profile and Outcome in a Pediatric Cohort
by Silvia Passantino, Serena Chiellino, Francesca Girolami, Mattia Zampieri, Giovanni Battista Calabri, Gaia Spaziani, Elena Bennati, Giulio Porcedda, Elena Procopio, Iacopo Olivotto and Silvia Favilli
Diagnostics 2023, 13(24), 3674; https://doi.org/10.3390/diagnostics13243674 - 15 Dec 2023
Cited by 1 | Viewed by 976
Abstract
Background: Cardiac involvement is reported in a significant proportion of patients with classical organic acidurias (OAs), contributing to disability and premature death. Different cardiac phenotypes have been described, among which dilated cardiomyopathy (DCM) is predominant. Despite recent progress in diagnosis and treatment, the [...] Read more.
Background: Cardiac involvement is reported in a significant proportion of patients with classical organic acidurias (OAs), contributing to disability and premature death. Different cardiac phenotypes have been described, among which dilated cardiomyopathy (DCM) is predominant. Despite recent progress in diagnosis and treatment, the natural history of patients with OAs remains unresolved, specifically with regard to the impact of cardiac complications. We therefore performed a retrospective study to address this issue at our Referral Center for Pediatric Inherited Errors of Metabolism. Methods: Sixty patients with OAs (propionic (PA), methylmalonic (MMA) and isovaleric acidemias and maple syrup urine disease) diagnosed from 2000 to 2022 were systematically assessed at baseline and at follow-up. Results: Cardiac anomalies were found in 23/60 OA patients, all with PA or MMA, represented by DCM (17/23 patients) and/or acquired long QT syndrome (3/23 patients). The presence of DCM was associated with the worst prognosis. The rate of occurrence of major adverse cardiac events (MACEs) at 5 years was 55% in PA with cardiomyopathy; 35% in MMA with cardiomyopathy; and 23% in MMA without cardiomyopathy. Liver transplantation was performed in seven patients (12%), all with PA or MMA, due to worsening cardiac impairment, and led to the stabilization of metabolic status and cardiac function. Conclusions: Cardiac involvement was documented in about one third of children diagnosed with classical OAs, confined to PA and MMA, and was often associated with poor outcome in over 50%. Etiological diagnosis of OAs is essential in guiding management and risk stratification. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Prevalence of OAS in our study cohort.</p> Full article ">Figure 2
<p>Dilated cardiomyopathy in propionic acidemia in 12-year-old patient. (<b>A</b>) Echocardiography, M-Mode short axis: left ventricle is dilated, with low ejection fraction. (<b>B</b>) Cardiac Magnetic resonance: dilated left ventricle without fibrosis. (<b>C</b>) Electrocardiography: sinus rhythm, HR of 61 beats per minute. Qtc interval prolongation (480 msec).</p> Full article ">Figure 3
<p>Kaplan–Meier survival analysis showing impaired survival (due to all-cause mortality) in patients with cardiac involvement and without CI involvement. Time zero is defined as time at diagnosis of metabolic disorder.</p> Full article ">
21 pages, 721 KiB  
Review
Advancing Colorectal Cancer Diagnosis with AI-Powered Breathomics: Navigating Challenges and Future Directions
by Ioannis K. Gallos, Dimitrios Tryfonopoulos, Gidi Shani, Angelos Amditis, Hossam Haick and Dimitra D. Dionysiou
Diagnostics 2023, 13(24), 3673; https://doi.org/10.3390/diagnostics13243673 - 15 Dec 2023
Cited by 2 | Viewed by 1875
Abstract
Early detection of colorectal cancer is crucial for improving outcomes and reducing mortality. While there is strong evidence of effectiveness, currently adopted screening methods present several shortcomings which negatively impact the detection of early stage carcinogenesis, including low uptake due to patient discomfort. [...] Read more.
Early detection of colorectal cancer is crucial for improving outcomes and reducing mortality. While there is strong evidence of effectiveness, currently adopted screening methods present several shortcomings which negatively impact the detection of early stage carcinogenesis, including low uptake due to patient discomfort. As a result, developing novel, non-invasive alternatives is an important research priority. Recent advancements in the field of breathomics, the study of breath composition and analysis, have paved the way for new avenues for non-invasive cancer detection and effective monitoring. Harnessing the utility of Volatile Organic Compounds in exhaled breath, breathomics has the potential to disrupt colorectal cancer screening practices. Our goal is to outline key research efforts in this area focusing on machine learning methods used for the analysis of breathomics data, highlight challenges involved in artificial intelligence application in this context, and suggest possible future directions which are currently considered within the framework of the European project ONCOSCREEN. Full article
(This article belongs to the Special Issue Artificial Intelligence in Gastrointestinal Disease: Diagnosis and Management)
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<p>Schematic representation of the topics discussed within the scope of this study.</p> Full article ">
20 pages, 9173 KiB  
Article
Design and Simulate Intracranial Support to Guide Maxillo Surgery: A Study Based on Bioengineering
by Maria Giulia Cristofaro, Elvis Kallaverja, Francesco Ferragina and Ida Barca
Diagnostics 2023, 13(24), 3672; https://doi.org/10.3390/diagnostics13243672 - 14 Dec 2023
Viewed by 1042
Abstract
Background: Intraoperative navigation allows for the creation of a real-time relationship between the anatomy imagined during diagnosis/planning and the site of surgical interest. This procedure takes place by identifying and registering trustworthy anatomical markers on planning images and using a point locator during [...] Read more.
Background: Intraoperative navigation allows for the creation of a real-time relationship between the anatomy imagined during diagnosis/planning and the site of surgical interest. This procedure takes place by identifying and registering trustworthy anatomical markers on planning images and using a point locator during the operation. The locator is calibrated in the workspace by placing a Dynamic Reference Frame (DRF) sensor. Objective: This study aims to calculate the localization accuracy of an electromagnetic locator of neuro-maxillofacial surgery, moving the standard sensor position to a different position more suitable for maxillofacial surgery. Materials and Methods: The upper dental arch was chosen as an alternative fixed point for the positioning of the sensor. The prototype of a bite support device was designed and generated via 3D printing. CT images of a skull phantom with 10 anatomical landmarks were acquired. The testing procedure consisted of 10 measurements for each position of the sensor: precisely 10 measurements with the sensor placed on the forehead and 10 measurements with the sensor placed on the bite support device. It also evaluated the localization error by comparing the two procedures. Results: The localization error, when the sensor was placed on the bite support device, was lower in the sphere located on the temporal bone. It was the same in the spheres located on the maxillary bone. The test analysis of the data of the new device showed that it is reliable; the tests are reproducible and can be considered as accurate as the traditional ones. In addition, the sensor mounted on this device has proven to be slightly superior in terms of accuracy and accuracy in areas such as the middle third of the face and jaw. Discussion and Conclusion: The realization of the bite support device allowed the sensor to change position concerning its natural site. This procedure allows us to explore structures, such as the frontal site, which were initially difficult to approach with neuronavigation and improves the approach to midface structures, already studied with neuronavigation. The new calibration, with the position of the sensor on the support device in the same reference points sphere, highlighted the reduction in the location error. We can say that the support proposed in this study lays the foundations for a new navigation approach for patients in maxillofacial surgery, by changing the position of the sensor. It has strong points in improving the localization error for some reference points without determining disadvantages both in the calibration and in the surgical impediment. Full article
(This article belongs to the Section Point-of-Care Diagnostics and Devices)
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<p>CT scanning (axial, sagittal, coronal, and 3D) with the dental device, created using CAD software. Green points—Fiducal Landmarks for calibration (maxillo malar suture and anterior nasal spine).</p> Full article ">Figure 2
<p>Volume Cropping.</p> Full article ">Figure 3
<p>Dental structure of the phantom.</p> Full article ">Figure 4
<p>Bite obtained from the phantom’s upper dental structure.</p> Full article ">Figure 5
<p>Sensor support.</p> Full article ">Figure 6
<p>Prototype.</p> Full article ">Figure 7
<p>Distance between the spheres is indicated by letters. The distances between the spheres measured with the software: (a) frontal right–left, (b) temporal right–left, (c) maxillary right–left, (d) premaxilla right–left, (e) glabella–anterior nasal spine, (f) glabella–right maxilla, (g) glabella–left maxilla.</p> Full article ">Figure 8
<p>Spheres marked with numbers.</p> Full article ">Figure 9
<p>Example: measure distance.</p> Full article ">Figure 10
<p>Error localization sphere nr.5.</p> Full article ">Figure 11
<p>Target Registration Error. Black ‘X’ is the sphere shown on the TC scan. Green ‘X’ is the real-time position of the navigator pointer located on the surface of the sphere.</p> Full article ">Figure 12
<p>Box plot sphere location error. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 13
<p>Box plot comparison of calibration. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 14
<p>Box plot sphere location error. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 15
<p>Box plot comparison of calibration. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 16
<p>Box plot distance error. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 17
<p>Box plot comparison of calibration. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 18
<p>Box plot distance error. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 19
<p>Box plot comparison of calibration. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 20
<p>Box plot distance error. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 21
<p>Box plot comparison of calibration. The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend. Instead, the white bullets indicate the outliers.</p> Full article ">Figure 22
<p>Box plot distance median. Difference between the sensor on the forehead and the bite support (distance). The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend.</p> Full article ">Figure 23
<p>Box plot distance sphere median error. Difference between the sensor on the forehead and the bite support (sphere). The bars indicate the minimum and maximum values of a certain range, without outliers. The orange line indicates the median of the data and gives an idea of the central error trend.</p> Full article ">
4 pages, 205 KiB  
Editorial
AI/ML-Based Medical Image Processing and Analysis
by Jaafar Alghazo and Ghazanfar Latif
Diagnostics 2023, 13(24), 3671; https://doi.org/10.3390/diagnostics13243671 - 14 Dec 2023
Cited by 2 | Viewed by 2216
Abstract
The medical field is experiencing remarkable advancements, notably with the latest technologies—artificial intelligence (AI), big data, high-performance computing (HPC), and high-throughput computing (HTC)—that are in place to offer groundbreaking solutions to support medical professionals in the diagnostic process [...] Full article
(This article belongs to the Special Issue AI/ML-Based Medical Image Processing and Analysis)
18 pages, 1681 KiB  
Article
The Challenge to Stabilize, Extract and Analyze Urinary Cell-Free DNA (ucfDNA) during Clinical Routine
by Ivonne Nel, Carolin Münch, Saikal Shamkeeva, Mitja L. Heinemann, Berend Isermann and Bahriye Aktas
Diagnostics 2023, 13(24), 3670; https://doi.org/10.3390/diagnostics13243670 - 14 Dec 2023
Cited by 1 | Viewed by 1455
Abstract
Background: The “Liquid Biopsy” has become a powerful tool for cancer research during the last decade. Circulating cell-free DNA (cfDNA) that originates from tumors has emerged as one of the most promising analytes. In contrast to plasma-derived cfDNA, only a few studies have [...] Read more.
Background: The “Liquid Biopsy” has become a powerful tool for cancer research during the last decade. Circulating cell-free DNA (cfDNA) that originates from tumors has emerged as one of the most promising analytes. In contrast to plasma-derived cfDNA, only a few studies have investigated urinary cfDNA. One reason might be rapid degradation and hence inadequate concentrations for downstream analysis. In this study, we examined the stability of cfDNA in urine using different methods of preservation under various storage conditions. Methodology: To mimic patient samples, a pool of healthy male and female urine donors was spiked with a synthetic cfDNA reference standard (fragment size 170 bp) containing the T790M mutation in the EGFR gene. Spiked samples were preserved with three different buffers and with no buffer over four different storage periods (0 h; 4 h; 12 h; 24 h) at room temperature vs. 4 °C. The preservatives used were Urinary Analyte Stabilizer (UAS, Novosanis, Wijnegem, Belgium), Urine Conditioning Buffer (UCB, Zymo, Freiburg, Germany) and a self-prepared buffer called “AlloU”. CfDNA was extracted using the QIAamp MinElute ccfDNA Mini Kit (Qiagen, Hilden, Germany). CfDNA concentration was measured using the Qubit™ 4 fluorometer (Thermo Fisher Scientific, Waltham, MA, USA). Droplet digital PCR (ddPCR) was used for detection and quantification of the T790M mutation. Results: Almost no spiked cfDNA was recoverable from samples with no preservation buffer and the T790M variant was not detectable in these samples. These findings indicate that cfDNA was degraded below the detection limit by urinary nucleases. Stabilizing buffers showed varying efficiency in preventing this degradation. The most effective stabilizing buffer under all storage conditions was the UAS, enabling adequate recovery of the T790M variant using ddPCR. Conclusion: From a technical point of view, stabilizing buffers and adequate storage conditions are a prerequisite for translation of urinary cfDNA diagnostics into clinical routine. Full article
(This article belongs to the Topic Biomarker Development and Application)
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<p>cfDNA levels in ng for female (F) vs. male (M) urine donors were not significantly different (<span class="html-italic">p</span> = 0.15; mean females: 19.75 ± 31.44 ng; mean males: 5.37 ± 5.85 ng).</p> Full article ">Figure 2
<p>cfDNA dynamics in the NC and the samples spiked with cfDNA reference standard are depicted as mean values of total cfDNA content with their standard deviation for (<b>A</b>) no buffer, (<b>B</b>) buffer UAS, (<b>C</b>) buffer AlloU and (<b>D</b>) buffer UCB. The cfDNA is shown in ng after storage periods of 0 h, 4 h, 12 h and 24 h at room temperature (RT, red) and fridge temperature (4 °C, blue). The lighter colors show cfDNA levels of the NC. * indicates level of significance <span class="html-italic">p</span> ≤ 0.05 between total cfDNA content at consecutive time points.</p> Full article ">Figure 3
<p>Comparison of relative cfDNA levels (ng) in four different preserving conditions after 0 h, 4 h, 12 h and 24 h at (<b>A</b>) room temperature (RT) and (<b>B</b>) 4 °C. The measured cfDNA levels in ng of the negative controls were subtracted from the cfDNA levels of the spiked samples. No buffer—blue, UAS—orange, AlloU—green, UCB—pink. After 24 h at RT, UAS resulted in the highest relative cfDNA yield of 9.12 ng from 3 mL urine, which was significantly higher compared to 3.82 ng recovered with AllUo (<span class="html-italic">p</span> = 0.015), but not significantly different from the initial level at 0 h (<span class="html-italic">p</span> = 0.169). Further, using AlloU revealed significantly decreased cfDNA levels after 24 h at RT (<span class="html-italic">p</span> = 0.007). After 24 h at 4 °C, however, UAS showed a relative cfDNA yield of only 4.28 ng, which was a non-significant decrease compared to the initial level (<span class="html-italic">p</span> = 0.248), but inferior to AlloU with 11.21 ng in 3 mL urine after 24 h (<span class="html-italic">p</span> = 0.034). * indicates level of significance <span class="html-italic">p</span> ≤ 0.05 between cfDNA levels.</p> Full article ">Figure 4
<p>Comparison of cfDNA levels in the NC samples with the four conditions after 0 h, 4 h, 12 h and 24 h at (<b>A</b>) room temperature (RT) and (<b>B</b>) 4 °C. No buffer—blue, UAS—orange, AlloU—green, UCB—pink. * indicates level of significance <span class="html-italic">p</span> ≤ 0.05 between cfDNA levels.</p> Full article ">Figure 5
<p>Fractional abundance (FA) of T790M mutation in samples buffered with UAS and AlloU. The samples were measured using ddPCR after storage periods of 0 h, 4 h and 24 h at room temperature (RT, solid lines) and 4 °C (dotted lines). All samples were spiked with cfDNA reference standard carrying the T790M variant at 5% AF. UAS—orange, AlloU—green.</p> Full article ">
15 pages, 4918 KiB  
Article
Computer-Aided Diagnosis of Laryngeal Cancer Based on Deep Learning with Laryngoscopic Images
by Zhi-Hui Xu, Da-Ge Fan, Jian-Qiang Huang, Jia-Wei Wang, Yi Wang and Yuan-Zhe Li
Diagnostics 2023, 13(24), 3669; https://doi.org/10.3390/diagnostics13243669 - 14 Dec 2023
Cited by 1 | Viewed by 1627
Abstract
Laryngeal cancer poses a significant global health burden, with late-stage diagnoses contributing to reduced survival rates. This study explores the application of deep convolutional neural networks (DCNNs), specifically the Densenet201 architecture, in the computer-aided diagnosis of laryngeal cancer using laryngoscopic images. Our dataset [...] Read more.
Laryngeal cancer poses a significant global health burden, with late-stage diagnoses contributing to reduced survival rates. This study explores the application of deep convolutional neural networks (DCNNs), specifically the Densenet201 architecture, in the computer-aided diagnosis of laryngeal cancer using laryngoscopic images. Our dataset comprised images from two medical centers, including benign and malignant cases, and was divided into training, internal validation, and external validation groups. We compared the performance of Densenet201 with other commonly used DCNN models and clinical assessments by experienced clinicians. Densenet201 exhibited outstanding performance, with an accuracy of 98.5% in the training cohort, 92.0% in the internal validation cohort, and 86.3% in the external validation cohort. The area under the curve (AUC) values consistently exceeded 92%, signifying robust discriminatory ability. Remarkably, Densenet201 achieved high sensitivity (98.9%) and specificity (98.2%) in the training cohort, ensuring accurate detection of both positive and negative cases. In contrast, other DCNN models displayed varying degrees of performance degradation in the external validation cohort, indicating the superiority of Densenet201. Moreover, Densenet201’s performance was comparable to that of an experienced clinician (Clinician A) and outperformed another clinician (Clinician B), particularly in the external validation cohort. Statistical analysis, including the DeLong test, confirmed the significance of these performance differences. Our study demonstrates that Densenet201 is a highly accurate and reliable tool for the computer-aided diagnosis of laryngeal cancer based on laryngoscopic images. The findings underscore the potential of deep learning as a complementary tool for clinicians and the importance of incorporating advanced technology in improving diagnostic accuracy and patient care in laryngeal cancer diagnosis. Future work will involve expanding the dataset and further optimizing the deep learning model. Full article
(This article belongs to the Special Issue Artificial Intelligence in Medical Image Processing and Disease Diagnosis)
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<p>The experimental flowchart of this study.</p> Full article ">Figure 2
<p>(<b>A</b>) Line is a benign laryngoscopy image, while line (<b>B</b>) is a malignant laryngoscopy image. The first image in line (<b>A</b>) is a polyp case, the second is a papilloma, the third is a tuberculosis, and the fourth is a granulomatous lesion.</p> Full article ">Figure 3
<p>The network structure diagram of Densenet201.</p> Full article ">Figure 4
<p>Figure (<b>A</b>) represents the loss decrease curve, while Figure (<b>B</b>) represents the accuracy change curve.</p> Full article ">Figure 5
<p>ROC of multi-model training process (<b>A</b>), internal validation (<b>B</b>), external validation (<b>C</b>), and comparison of ROC between external validation and clinical models in Densenet201 (<b>D</b>).</p> Full article ">Figure 6
<p>Confusion matrix between internal validation group and external validation group of Densenet201.</p> Full article ">
11 pages, 1235 KiB  
Article
Clinical Evaluation of Direct Reverse Transcription PCR for Detection of SARS-CoV-2 Compared to Conventional RT-PCR in Patients with Positive Rapid Antigen Test Results during Circulation of Emerging Viral Variants
by Ming-Jr Jian, Chi-Sheng Chen, Hsing-Yi Chung, Chih-Kai Chang, Cherng-Lih Perng and Hung-Sheng Shang
Diagnostics 2023, 13(24), 3668; https://doi.org/10.3390/diagnostics13243668 - 14 Dec 2023
Cited by 1 | Viewed by 1134
Abstract
The emergence of the Omicron (B.1.1.529) variant of SARS-CoV-2 has precipitated a new global wave of the COVID-19 pandemic. The rapid identification of SARS-CoV-2 infection is imperative for the effective mitigation of transmission. Diagnostic modalities such as rapid antigen testing and real-time reverse [...] Read more.
The emergence of the Omicron (B.1.1.529) variant of SARS-CoV-2 has precipitated a new global wave of the COVID-19 pandemic. The rapid identification of SARS-CoV-2 infection is imperative for the effective mitigation of transmission. Diagnostic modalities such as rapid antigen testing and real-time reverse transcription polymerase chain reaction (RT-PCR) offer expedient turnaround times of 10–15 min and straightforward implementation. This preliminary study assessed the correlation between outcomes of commercially available rapid antigen tests for home use and conventional reverse transcription polymerase chain reaction (RT-PCR) assays using a limited set of clinical specimens. Patients aged 5–99 years presenting to the emergency department for SARS-CoV-2 testing were eligible for enrollment (n = 5652). Direct PCR and conventional RT-PCR were utilized for the detection of SARS-CoV-2. The entire cohort of 5652 clinical specimens was assessed by both modalities to determine the clinical utility of the direct RT-PCR assay. Timely confirmation of SARS-CoV-2 infection may attenuate viral propagation and guide therapeutic interventions. Additionally, direct RT-PCR as a secondary confirmatory test for at-home rapid antigen test results demonstrated sensitivity comparable to conventional RT-PCR, indicating utility for implementation in laboratories globally, especially in resource-limited settings with constraints on reagents, equipment, and skilled personnel. In summary, direct RT-PCR enables the detection of SARS-CoV-2 with a sensitivity approaching that of conventional RT-PCR while offering expedient throughput and shorter turnaround times. Moreover, direct RT-PCR provides an open-source option for diagnostic laboratories worldwide, particularly in low- and middle-income countries. Full article
(This article belongs to the Special Issue Detection and Assessment of SARS-CoV-2 Variants)
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<p>Ct values obtained from RT-PCR and direct RT-PCR of positive at-home rapid antigen test samples. (<b>A</b>) RT-PCR Ct value plot ordered by Ct value. (<b>B</b>) Direct RT-PCR Ct value plot ordered by Ct value. (<b>C</b>) Comparison of RT-PCR and direct RT-PCR test results.</p> Full article ">Figure 2
<p>Correlation of Ct values of clinically positive specimens by RT-PCR and direct RT-PCR. The shade of the color represents the number of observations.</p> Full article ">Figure 3
<p>Flow chart for diagnosis of RAT-positive patients. RAT: rapid antigen test; RT-PCR: reverse transcription-polymerase chain reaction; POCT: point-of-care testing.</p> Full article ">
17 pages, 5885 KiB  
Article
Artificial Intelligence Image Recognition System for Preventing Wrong-Site Upper Limb Surgery
by Yi-Chao Wu, Chao-Yun Chang, Yu-Tse Huang, Sung-Yuan Chen, Cheng-Hsuan Chen and Hsuan-Kai Kao
Diagnostics 2023, 13(24), 3667; https://doi.org/10.3390/diagnostics13243667 - 14 Dec 2023
Viewed by 1325
Abstract
Our image recognition system employs a deep learning model to differentiate between the left and right upper limbs in images, allowing doctors to determine the correct surgical position. From the experimental results, it was found that the precision rate and the recall rate [...] Read more.
Our image recognition system employs a deep learning model to differentiate between the left and right upper limbs in images, allowing doctors to determine the correct surgical position. From the experimental results, it was found that the precision rate and the recall rate of the intelligent image recognition system for preventing wrong-site upper limb surgery proposed in this paper could reach 98% and 93%, respectively. The results proved that our Artificial Intelligence Image Recognition System (AIIRS) could indeed assist orthopedic surgeons in preventing the occurrence of wrong-site left and right upper limb surgery. At the same time, in future, we will apply for an IRB based on our prototype experimental results and we will conduct the second phase of human trials. The results of this research paper are of great benefit and research value to upper limb orthopedic surgery. Full article
(This article belongs to the Special Issue Artificial Intelligence in Orthopedic Surgery and Sport Medicine)
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<p>Categories of surgical site errors [<a href="#B3-diagnostics-13-03667" class="html-bibr">3</a>].</p> Full article ">Figure 2
<p>Marking and barcode scanning.</p> Full article ">Figure 3
<p>Labeling using the LabelImg software.</p> Full article ">Figure 4
<p>ResNet50 model [<a href="#B34-diagnostics-13-03667" class="html-bibr">34</a>].</p> Full article ">Figure 5
<p>YoloV4 model [<a href="#B35-diagnostics-13-03667" class="html-bibr">35</a>].</p> Full article ">Figure 6
<p>Example with <span class="html-italic">Conf_threshold</span> larger than 0.9.</p> Full article ">Figure 6 Cont.
<p>Example with <span class="html-italic">Conf_threshold</span> larger than 0.9.</p> Full article ">Figure 7
<p>Accuracy with input size <math display="inline"><semantics> <mrow> <mn>608</mn> <mo>×</mo> <mn>608</mn> </mrow> </semantics></math>.</p> Full article ">Figure 8
<p>Recall with input sizes <math display="inline"><semantics> <mrow> <mn>608</mn> <mo>×</mo> <mn>608</mn> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <mn>512</mn> <mo>×</mo> <mn>512</mn> </mrow> </semantics></math>, and <math display="inline"><semantics> <mrow> <mn>416</mn> <mo>×</mo> <mn>416</mn> </mrow> </semantics></math>.</p> Full article ">Figure 9
<p>Accuracy with input size <math display="inline"><semantics> <mrow> <mn>512</mn> <mo>×</mo> <mn>512</mn> </mrow> </semantics></math>.</p> Full article ">Figure 10
<p>Accuracy with input size <math display="inline"><semantics> <mrow> <mn>416</mn> <mo>×</mo> <mn>416</mn> </mrow> </semantics></math>.</p> Full article ">Figure 11
<p><span class="html-italic">Accuracy</span> under AIIRS and ResNet50 with <span class="html-italic">Conf_threshold</span> of 0.9 (the orange color represents AIIRS and the blue color represents ResNet50).</p> Full article ">Figure 12
<p><span class="html-italic">Recall</span> under AIIRS and ResNet50 with <span class="html-italic">Conf_threshold</span> of 0.9 (the orange color represents AIIRS and the blue color represents ResNet50).</p> Full article ">
17 pages, 4181 KiB  
Review
Focus on Paediatric Restrictive Cardiomyopathy: Frequently Asked Questions
by Mattia Zampieri, Chiara Di Filippo, Chiara Zocchi, Vera Fico, Cristina Golinelli, Gaia Spaziani, Giovanni Calabri, Elena Bennati, Francesca Girolami, Alberto Marchi, Silvia Passantino, Giulio Porcedda, Guglielmo Capponi, Alessia Gozzini, Iacopo Olivotto, Luca Ragni and Silvia Favilli
Diagnostics 2023, 13(24), 3666; https://doi.org/10.3390/diagnostics13243666 - 14 Dec 2023
Viewed by 1479
Abstract
Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular pathophysiology determined by increased myocardial stiffness. While suspicion of RCM is initially raised by clinical evaluation and supported by electrocardiographic and echocardiographic findings, invasive hemodynamic evaluation is often required for diagnosis and management of patients [...] Read more.
Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular pathophysiology determined by increased myocardial stiffness. While suspicion of RCM is initially raised by clinical evaluation and supported by electrocardiographic and echocardiographic findings, invasive hemodynamic evaluation is often required for diagnosis and management of patients during follow-up. RCM is commonly associated with a poor prognosis and a high incidence of heart failure, and PH is reported in paediatric patients with RCM. Currently, only a few therapies are available for specific RCM aetiologies. Early referral to centres for advanced heart failure treatment is often necessary. The aim of this review is to address questions frequently asked when facing paediatric patients with RCM, including issues related to aetiologies, clinical presentation, diagnostic process and prognosis. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Suggested flow-chart for initial approach to patient with heart failure and suspected restrictive cardiomyopathy. CXR chest X-ray, ECG electrocardiogram; MR magnetic resonance, Nt-pro-BNP N-terminal pro B type Natriuretic Peptide, RCM-restrictive cardiomyopathy.</p> Full article ">Figure 2
<p>A 6-year-old boy with restrictive cardiomyopathy. Electrocardiogram shows abnormal P waves suggestive of atrial enlargement and abnormal ventricular repolarization suggestive of biventricular pressure overload.</p> Full article ">Figure 3
<p>(<b>A</b>) Chest X-ray, 8-year-old boy with hypertrophic-restrictive cardiomyopathy and congestive heart failure. (<b>B</b>) Echocardiography apical 4-chambers view, 11-year-old girl with restrictive cardiomyopathy, normal ventricular volumes, preserved ejection fraction and severe atrial dilatation; we can appreciate the presence of an implantable cardiac defibrillator lead. (<b>C</b>) Echocardiography parasternal long axis view, 6-year-old boy with restrictive cardiomyopathy associated to severe left atrial dilatation.</p> Full article ">Figure 4
<p>Main aetiologies of restrictive cardiomyopathy according to the age of disease presentation.</p> Full article ">Figure 5
<p>Flow-chart management of paediatric restrictive cardiomyopathy). Right heart catheterization is usually indicated for all patients referred for HT. However, it is useful to stratify prognosis in patients in NYHA class I to II since severe PH and low cardiac output can develop with mild or subtle symptoms. DPG, diastolic pulmonary gradient; HT, heart transplantation; PVR, pulmonary vascular resistance; RHC, right heart catheterization; TPG, transpulmonary gradient.</p> Full article ">
14 pages, 654 KiB  
Systematic Review
Efficacy of Handheld Ultrasound in Medical Education: A Comprehensive Systematic Review and Narrative Analysis
by Mariam Haji-Hassan, Roxana-Denisa Capraș and Sorana D. Bolboacă
Diagnostics 2023, 13(24), 3665; https://doi.org/10.3390/diagnostics13243665 - 14 Dec 2023
Viewed by 1336
Abstract
Miniaturization has made ultrasound (US) technology ultraportable and, in association with their relatively low cost, made handheld devices attractive for medical education training programs. However, performing an ultrasound requires complex skills, and it is unclear whether handheld devices are suitable for the training [...] Read more.
Miniaturization has made ultrasound (US) technology ultraportable and, in association with their relatively low cost, made handheld devices attractive for medical education training programs. However, performing an ultrasound requires complex skills, and it is unclear whether handheld devices are suitable for the training of novices. Our study aimed to identify to what extent handheld US devices can be employed in medical undergraduates’ and residents’ education. We selected studies that evaluate the results obtained by students and/or residents who have participated in ultrasound training programs using handheld devices. The studies were included if they reported post-test (pre-test optional) achievements or a comparison with a control group (a group of experts or novices who underwent a different intervention). Twenty-six studies were selected, and their characteristics were summarized. Handheld ultrasound devices were used in training programs to learn echocardiography, abdominal, and/or musculoskeletal ultrasound. Statistically significant progress was noted in the ability of naïve participants to capture and interpret ultrasound images, but training duration influenced the outcomes. While ultrasound training using handheld devices has proven to be feasible for various body regions and purposes (e.g., better understanding of anatomy, clinical applications, etc.), the long-term impacts of handheld education interventions must be considered in addition to the short-term results to outline guidelines for targeted educational needs. Full article
(This article belongs to the Special Issue The Use of Portable Devices in Emergency Medicine)
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<p>PRISMA flow diagram (from records identification to inclusion).</p> Full article ">
12 pages, 702 KiB  
Article
Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels in Breast Cancer Risk in Mali: A Case–Control Study
by Aboubacar D. T. Bissan, Madani Ly, Awo Emmanuela H. Amegonou, Fatoumata M. Sidibe, Bocary S. Koné, Nènè Oumou K. Barry, Madiné Tall, Lassana G. Timbiné, Bourèma Kouriba, Pascal Reynier and Zahra Ouzzif
Diagnostics 2023, 13(24), 3664; https://doi.org/10.3390/diagnostics13243664 - 14 Dec 2023
Cited by 1 | Viewed by 1084
Abstract
(1) Background: Breast cancer is the most prevalent cancer found in women in Mali. The aim of the current study was to determine the association between metabolites circulating in the blood, 25(OH)D and 1,25(OH)2D, and vitamin D levels with the risk [...] Read more.
(1) Background: Breast cancer is the most prevalent cancer found in women in Mali. The aim of the current study was to determine the association between metabolites circulating in the blood, 25(OH)D and 1,25(OH)2D, and vitamin D levels with the risk of breast cancer in Malian women. (2) Methods: We conducted a prospective case–control study from August 2021 to March 2022. Control subjects were matched to cases according to age (within 5 years). The patients’ clinical stage was determined by the oncologist according to the tumour–nodes–metastasis (TNM) classification system. (3) Results: We observed no differences in the mean 25(OH)D (p = 0.221) and 1,25(OH)2D (p = 0.285) between cases and controls. However, our findings indicate a more pronounced inverse association in the first level of plasma 25(OH)D, while the risk function decreases at higher levels. This observation takes strength with 1,25(OH)2D by a significant association between the first quartile and breast cancer as a risk factor (p = 0.03; OR = 71.84; CI: 1.36–3785.34). (4) Conclusions: These outcomes showed a possible association between 25(OH)D and 1,25(OH)2D in decreasing the risk of breast cancer. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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<p>Plasma levels of 25(OH)D (<b>A</b>) and 1,25(OH)<sub>2</sub>D (<b>B</b>) in women with and without breast cancer. m: mean.</p> Full article ">Figure 2
<p>Scatterplot of the relationship between circulating levels of 25(OH)D and 1,25(OH)<sub>2</sub>D.</p> Full article ">
19 pages, 6429 KiB  
Article
Rare Pancreatic/Peripancreatic Cystic Lesions Can Be Accurately Characterized by EUS with Through-the-Needle Biopsy—A Unique Pictorial Essay with Clinical and Histopathological Correlations
by Maria Cristina Conti Bellocchi, Erminia Manfrin, Alessandro Brillo, Laura Bernardoni, Andrea Lisotti, Pietro Fusaroli, Alice Parisi, Sokol Sina, Antonio Facciorusso, Armando Gabbrielli and Stefano Francesco Crinò
Diagnostics 2023, 13(24), 3663; https://doi.org/10.3390/diagnostics13243663 - 14 Dec 2023
Cited by 1 | Viewed by 1171
Abstract
Due to their aspecific macroscopic appearance, uncommon pancreatic cystic lesions (PCLs) are often misdiagnosed as mucinous lesions and improperly resected. We aimed to evaluate the endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) capacity of the preoperative diagnosis of uncommon PCLs. Overall, 136 patients with [...] Read more.
Due to their aspecific macroscopic appearance, uncommon pancreatic cystic lesions (PCLs) are often misdiagnosed as mucinous lesions and improperly resected. We aimed to evaluate the endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) capacity of the preoperative diagnosis of uncommon PCLs. Overall, 136 patients with PCLs who underwent EUS-TTNB between 2016 and 2022 were retrospectively identified. Common histotypes (e.g., IPMN, serous cystadenoma, and mucinous cystadenoma) were excluded and 26 (19.1%) patients (15 female, mean age 52.9 ± 10.4) were analyzed. The EUS findings, adverse events (AEs), and TTNB outcomes in uncommon PCLs were evaluated. The cysts histotype was accurately diagnosed by TTNB in 24/26 (92.3%) cases (seven cystic neuroendocrine tumors, four squamoid cysts, three acinar cells cystadenomas, two lymphoepithelial cysts, two mucinous non-neoplastic cysts, two bronchogenic cysts, two cystic lymphangiomas, one solid-pseudopapillary neoplasm, and one schwannoma). In the remaining two cases, lymphangioma was eventually diagnosed after resection. Surgery was performed in 15/26 (57.7%) patients. The mean follow-up of non-surgical patients was 32.5 months. One severe acute case of pancreatitis (3.8%) that required surgery occurred after EUS-TTNB. Uncommon pancreatic/peripancreatic lesions represent the 19.1% of PCLs in our series, with mainly benign histotypes. TTNB demonstrated a high diagnostic performance with a low rate of AEs in this setting, representing a reliable tool with which to avoid useless surgery. Full article
(This article belongs to the Special Issue Endoscopic Ultrasound Guided Tissue Sampling of Tumors)
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<p>Flowchart of the study. EUS-TTNB, endoscopic ultrasound-guided through-the-needle biopsy; PCLs, pancreatic cystic lesions; cNET, cystic neuroendocrine tumors; SCOP, squamoid cyst of pancreatic duct; ACT, acinar cystic transformation; LEC, lymphoepithelial cyst; SMC, simple mucinous cyst; BC, bronchogenic cyst; SPN, solid pseudopapillary neoplasm; SWN, schwannoma; CL, cystic lymphangioma.</p> Full article ">Figure 2
<p>Cystic neuroendocrine neoplasm. Contrast-harmonic endoscopic ultrasound showing hyper-enhanced walls of an unilocular cyst (<b>A</b>). Endoscopic ultrasound-guided through-the-needle biopsy targeting the thickened walls (<b>B</b>). The cyst wall is almost completely composed of small, tightly packed epithelial cells (<b>C</b>) that stain intensely for the neuroendocrine marker Synaptophysin (<b>D</b>). Hematoxylin–eosin original magnification ×100 (<b>C</b>). Synaptophysin original magnification ×100 (<b>D</b>).</p> Full article ">Figure 3
<p>Squamoid cyst of pancreatic ducts. T2-weighted magnetic resonance imaging of a pancreatic cyst located in the head, with a nodule inside (<b>A</b>). The same cyst on an endoscopic ultrasound scan containing round vegetation that resulted in avascular at contrast-harmonic evaluation (<b>B</b>). The fibrous thin wall of the cyst is lined by stratified epithelium (<b>C</b>) without atypia and keratinization (<b>D</b>). Hematoxylin–eosin original magnification ×100 (<b>C</b>), ×200 (<b>D</b>).</p> Full article ">Figure 4
<p>Acinar Cystic Transformation. The whole mounted section of the multilocular cyst with fibrous wall (<b>A</b>). The lining epithelium is composed of cuboidal cells with abundant eosinophilic and granular cytoplasm, organized both in monolayer and acinar aggregates (<b>B</b>). The acinar markers BCL10 (<b>C</b>) and trypsin (<b>D</b>) are detected in epithelial cells. Hematoxylin–eosin original magnification ×40 (<b>A</b>), ×100 (<b>B</b>); BCL10 original magnification ×100 (<b>C</b>); Trypsin original magnification ×100 (<b>D</b>).</p> Full article ">Figure 5
<p>Cystic lymphangioma. Endoscopic ultrasound revealed an irregularly shaped multilocular cyst close to the pancreatic parenchyma, with a thin wall and septa (<b>A</b>). The aspirated fluid appeared as thick “milky” white-yellowish fluid (<b>B</b>). Numerous narrow lymphatic vessels lined by a cuboidal epithelium were separated by bundles of smooth muscle with few aggregates of lymphocytes (<b>C</b>). Immunolabelling for endothelial markers D2-40 (<b>D</b>) and CD31 (<b>E</b>). Bundles of smooth muscle actin (SMA) positive cells (<b>F</b>). Hematoxylin–eosin original magnification ×100 (<b>C</b>); D2-40 original magnification ×200 (<b>D</b>); CD31 original magnification ×200 (<b>E</b>); SMA original magnification ×200 (<b>F</b>).</p> Full article ">Figure 6
<p>Lymphoepithelial cyst. During the endoscopic ultrasound, a large cystic lesion with a regular wall and central thickened septum containing multiple round, echoic, and avascular floating balls after contrast injection was documented (<b>A</b>). The whole mounted section of the cyst wall forceps biopsy (<b>B</b>). Large aggregates of lymphoid cells are separated by squamous epithelial cells with sebaceous glands (<b>C</b>). Lymphocytes are highlighted by CD45 (<b>D</b>) and squamous cells by P63 (<b>E</b>) immunostaining, respectively. Hematoxylin–eosin original magnification ×40 (<b>B</b>), ×200 (<b>C</b>); CD45 original magnification ×100 (<b>D</b>); P63 original magnification ×100 (<b>E</b>).</p> Full article ">Figure 7
<p>Simple mucinous cyst. The whole fully mounted section of the cyst wall forceps biopsy (<b>A</b>). At higher magnification, the thick fibrous cist wall is lined with a monolayer of mucinous epithelial cells, without atypia (<b>B</b>). Hematoxylin–eosin original magnification ×40 (<b>A</b>), ×200 (<b>B</b>).</p> Full article ">Figure 8
<p>Bronchogenic cyst. Typical appearance of bronchogenic cyst on endoscopic ultrasound. The content of the cyst is similar to the liver parenchyma, with multiple white spots with a comet-tail artifact (<b>A</b>). The cyst wall biopsy shows a thick layer of eosinophilic, dense, hypocellular tissue beneath the pseudostratified epithelium (<b>B</b>). The epithelium lining the cyst wall is composed of ciliated and goblet cells (<b>C</b>). The subepithelial connective tissue is rich in smooth muscle fibers, which are Calponin-positive (<b>D</b>). Hematoxylin–eosin original magnification ×100 (<b>B</b>), ×400 (<b>C</b>); Calponin original magnification ×100 (<b>D</b>).</p> Full article ">Figure 9
<p>Solid pseudopapillary tumor. The whole mounted section of the cyst wall tissue fragment shows an altered histological architecture with an area of crash artefact caused by the forceps sampling procedure (<b>A</b>). In an area with better preserved morphology, the epithelial cells are round, small and tightly packed (<b>B</b>). Immunolabelling for β-catenin with aberrant nuclear positivity is conclusive for the diagnosis (<b>C</b>). Hematoxylin–eosin original magnification ×40 (<b>A</b>), ×200 (<b>B</b>); β-catenin original magnification ×200 (<b>C</b>).</p> Full article ">Figure 10
<p>Schwannoma. Computed tomography appearance of a large cystic lesion located between the second/third portion of the duodenum and the pancreatic head that appeared compressed and dislodged (<b>A</b>). On the endoscopic ultrasound, the lesion appeared as a round unilocular cyst with smooth borders and an irregular thickened wall (<b>B</b>). The whole mounted section of the cyst wall biopsy shows no epithelium lining the cyst (<b>C</b>). A well visible fascicle of spindle cells depicts the peripheral profile of the biopsy (<b>D</b>). Diffuse and intense immunolabelling for S100 in spindle cells (<b>E</b>). Hematoxylin–eosin original magnification ×40 (<b>C</b>), ×100 (<b>D</b>). S100 original magnification ×100 (<b>E</b>).</p> Full article ">
12 pages, 1271 KiB  
Review
Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders
by Michiel Beyens, Alessandro Toscano, Didier Ebo, Theo Gülen and Vito Sabato
Diagnostics 2023, 13(24), 3662; https://doi.org/10.3390/diagnostics13243662 - 14 Dec 2023
Cited by 1 | Viewed by 3832
Abstract
Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet [...] Read more.
Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet the consensus formula (i.e., an increase of 20% + 2). The upper limit of normal determined by the manufacturer is 11.4 ng/mL; however, this boundary has been the subject of debate. According to ECNM and AIM experts, the normal range of baseline tryptase should be 1 to 15 ng/mL. A genetic trait, hereditary alpha tryptasemia, characterized by an increased alpha coding TPSAB1 copy number is associated with a baseline value above 8 ng/mL. Elevated tryptase can also be found in chronic kidney disease, obesity, and hematological neoplasms. A tryptase > 20 ng/mL serves as a minor criterion to diagnose systemic mastocytosis and an increase in tryptase > 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome. The goal of this review is to demonstrate the (in)significance of tryptase using some clinical vignettes and to provide a practical guide on how to manage and interpret an elevated tryptase level. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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<p>(<b>A</b>) Proposed algorithm for patients with elevated bST. (<b>B</b>) Proposed algorithm for patients with mediator-related symptoms. MCAS: mast cell activation syndrome; MCA: mast cell activation; CKD: chronic kidney disease; HαT: hereditary alpha tryptasemia; bST: baseline serum tryptase; aST: acute serum tryptase; MIS: mastocytosis in the skin. * Indications for work-up include unexplained osteoporosis or MIS in adults.</p> Full article ">
13 pages, 2474 KiB  
Article
Attenuation Correction of Long Axial Field-of-View Positron Emission Tomography Using Synthetic Computed Tomography Derived from the Emission Data: Application to Low-Count Studies and Multiple Tracers
by Maria Elkjær Montgomery, Flemming Littrup Andersen, Sabrina Honoré d’Este, Nanna Overbeck, Per Karkov Cramon, Ian Law, Barbara Malene Fischer and Claes Nøhr Ladefoged
Diagnostics 2023, 13(24), 3661; https://doi.org/10.3390/diagnostics13243661 - 14 Dec 2023
Cited by 1 | Viewed by 1404
Abstract
Recent advancements in PET/CT, including the emergence of long axial field-of-view (LAFOV) PET/CT scanners, have increased PET sensitivity substantially. Consequently, there has been a significant reduction in the required tracer activity, shifting the primary source of patient radiation dose exposure to the attenuation [...] Read more.
Recent advancements in PET/CT, including the emergence of long axial field-of-view (LAFOV) PET/CT scanners, have increased PET sensitivity substantially. Consequently, there has been a significant reduction in the required tracer activity, shifting the primary source of patient radiation dose exposure to the attenuation correction (AC) CT scan during PET imaging. This study proposes a parameter-transferred conditional generative adversarial network (PT-cGAN) architecture to generate synthetic CT (sCT) images from non-attenuation corrected (NAC) PET images, with separate networks for [18F]FDG and [15O]H2O tracers. The study includes a total of 1018 subjects (n = 972 [18F]FDG, n = 46 [15O]H2O). Testing was performed on the LAFOV scanner for both datasets. Qualitative analysis found no differences in image quality in 30 out of 36 cases in FDG patients, with minor insignificant differences in the remaining 6 cases. Reduced artifacts due to motion between NAC PET and CT were found. For the selected organs, a mean average error of 0.45% was found for the FDG cohort, and that of 3.12% was found for the H2O cohort. Simulated low-count images were included in testing, which demonstrated good performance down to 45 s scans. These findings show that the AC of total-body PET is feasible across tracers and in low-count studies and might reduce the artifacts due to motion and metal implants. Full article
(This article belongs to the Special Issue Technical and Clinical Applications on Long-Axial-Field-of-View/Total Body PET-CT)
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<p>Illustrative sample patient with large banana artifact presented. Panels (<b>a</b>,<b>b</b>) show the normal CT (soft tissue window) and corresponding PET. The synthetic CT (sCT) and corresponding sPET are seen in (<b>c</b>,<b>d</b>). NAC PET is fused on top of the CT scan in (<b>e</b>), illustrating the mismatch between CT and emission data. The blue line represents the superior part of the liver at the time of CT scanning. Panel (<b>f</b>) shows the NAC PET used for synthesizing the sCT. (<b>g</b>,<b>h</b>) are MIPs of PET and sPET, respectively, and the voxel-wise relative difference between PET and sPET (<b>b</b>–<b>d</b>) is shown in (<b>i</b>). Note that the big deviation around the diaphragm is likely due to motion between CT scanning and PET emission.</p> Full article ">Figure 2
<p>This patient has a double shoulder implant resulting in severe streaking artifact in he CT image (<b>a</b>). The synthetic CT (<b>b</b>) does not express these artifacts. This artifact propagates by attenuation correction to the PET data. Panel (<b>e</b>) illustrates this by showing the relative difference between PET (<b>c</b>) and sPET (<b>d</b>).</p> Full article ">Figure 3
<p>These Seaborn boxplots show the mean relative difference between PET and sPET for selected organs for [<sup>18</sup>F]FDG (<b>a</b>) and [<sup>15</sup>O]H<sub>2</sub>O (<b>b</b>) scans for the two respective test cohorts. * Note that the [<sup>18</sup>F]FDG training data did not include the brain in most of the scans. In contrast, the [<sup>15</sup>O]H<sub>2</sub>O training data from the LAFOV scanner always included the brain.</p> Full article ">Figure 4
<p>Representative patient scan using NAC PET from [<sup>15</sup>O]H<sub>2</sub>O for sCT synthesis. Panel (<b>a</b>,<b>b</b>) shows a sample coronal slice from the CT and PET images, respectively. Panel (<b>c</b>) presents the NAC PET used for synthesis of sCT (<b>d</b>). The PET image reconstructed using sCT for attenuation correction is shown in (<b>e</b>), with the relative differences in PET (<b>b</b>) shown in panel (<b>f</b>). Note the motion artifact between CT and NAC PET resulting in a shadow above the liver in (<b>b</b>), also seen in (<b>e</b>) as a change in reconstructed activity in the lower lungs due to breathing.</p> Full article ">Figure 5
<p>Robustness towards different acquisition times can be observed for most organs down to 45 s and stay below 5% deviation on average even for 30 s. The exception is the brain, which is not well represented in the training data. The deviation in bone is also higher, most likely due to the big impact on bone values due to motion, e.g., in the rib cage. The training cohort noise level corresponded to the 90 s test data in image quality (red line).</p> Full article ">Figure 6
<p>Sample patient illustration CT (<b>a</b>), sCT derived from [<sup>18</sup>F]FDG PET NAC for 30 s, 45 s, 90 s, 180 s, and 300 s (<b>b</b>–<b>f</b>) and reconstructed sPET data using the derived sCT with increasing frame sizes: 30 s, 45 s, 90 s, 180 s, and 300 s (<b>g</b>–<b>k</b>).</p> Full article ">
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