Diagnostics

8 pages, 4409 KiB

Open AccessCase Report

Focal Myocarditis after Mild COVID-19 Infection in Athletes

by Ivana P. Nedeljkovic, Vojislav Giga, Marina Ostojic, Ana Djordjevic-Dikic, Tamara Stojmenovic, Ivan Nikolic, Nenad Dikic, Olga Nedeljkovic-Arsenovic, Ruzica Maksimovic, Milan Dobric, Nebojsa Mujovic and Branko Beleslin

Diagnostics 2021, 11(8), 1519; https://doi.org/10.3390/diagnostics11081519 - 23 Aug 2021

Cited by 6 | Viewed by 3824

Abstract

COVID-19 infection in athletes usually has a milder course, but in the case of complications, myocarditis and even sudden cardiac death may occur. We examined an athlete who felt symptoms upon returning to training after asymptomatic COVID-19 infection. Physical, laboratory, and echocardiography findings [...] Read more.

COVID-19 infection in athletes usually has a milder course, but in the case of complications, myocarditis and even sudden cardiac death may occur. We examined an athlete who felt symptoms upon returning to training after asymptomatic COVID-19 infection. Physical, laboratory, and echocardiography findings were normal. The cardiopulmonary exercise test was interrupted at submaximal effort due to severe dyspnea in the presence of reduced functional capacity in comparison to previous tests. Cardiac magnetic resonance (CMR) detected the focal myocarditis. After three months of recovery, CMR still revealed the presence of focal myocarditis and the persistence of decreased functional capacity. This case raises the question of screening athletes even after asymptomatic forms of COVID-19 infection. Full article

(This article belongs to the Topic Long-Term Health Monitoring with Physiological Signals)

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Resting ECG: sinus rhythm, heartrate = 95/min, AxQRS + 70, narrow QRS complex, R/S in leads D2, D3, aVF, r/S in leads V2, V3 with unifocal premature ventricular contraction with left bundle branch block morphology. Full article ">Figure 2
Baseline ECG before the cardiopulmonary test: sinus rhythm, heartrate = 80/min, AxQRS + 70, narrow QRS complex, R/S in leads D2, D3, aVF, r/S in leads V2, V3 without signs of hypertrophy. Full article ">Figure 3
Electrocardiogram during cardiopulmonary test: sinus tachycardia, heartrate = 166/min, AxQRS + 70, narrow QRS complex, R/S in leads D2, D3, aVF, r/S in leads V2, V3 with unifocal premature ventricular complexes with left bundle branch block morphology. Ambulatory 24-h ECG monitoring recorded 1535 PVCs and several episodes of trigeminia. Full article ">Figure 4
Cardiac magnetic resonance. (a) Four-chamber view ten minutes from the application of gadolinium with detection of the late gadolinium enhancement in the mid-lateral left ventricular wall. (b) Myocardial mapping (four-chamber view) showed elevated T1 signals of the mid-lateral left ventricular wall, with the enhancement of the adjacent pericardium also confirming the presence of pericarditis. Full article ">Figure 5
Control cardiac magnetic resonance three months after COVID-19 infection. (a) Persistence of late gadolinium enhancement in the basal and mid-lateral left ventricular wall. (b) Control CMR mapping detected increased values of postcontrast T2 subepicardial in the basal and medial part of the LV lateral wall in terms of myocarditis sequelae. The focal involvement of the pericardium along the lateral wall of the left ventricle can also be seen. Full article ">

29 pages, 2602 KiB

Open AccessReview

Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease

by Mădălina Ioana Moisi, Simona Gabriela Bungau, Cosmin Mihai Vesa, Camelia Cristina Diaconu, Tapan Behl, Manuela Stoicescu, Mirela Mărioara Toma, Cristiana Bustea, Cristian Sava and Mircea Ioachim Popescu

Diagnostics 2021, 11(8), 1518; https://doi.org/10.3390/diagnostics11081518 - 23 Aug 2021

Cited by 22 | Viewed by 5841

Abstract

The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context [...] Read more.

The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context of decreased renal function. In terms of mortality, CKD should be considered equivalent to ischemic coronary artery disease (CAD) and properly monitored. Vascular calcification, endothelial dysfunction, oxidative stress, anemia, and inflammatory syndrome represents the main uremic RF triggered by accumulation of the uremic toxins in CKD subjects. Proteinuria that appears due to kidney function decline may initiate an inflammatory status and alteration of the coagulation—fibrinolysis systems, favorizing acute coronary syndromes (ACS) occurrence. All these factors represent potential targets for future therapy that may improve CKD patient’s survival and prevention of CV events. Once installed, the CAD in CKD population is associated with negative outcome and increased mortality rate, that is the reason why discovering the complex pathophysiological connections between the two conditions and a proper control of the uremic RF are crucial and may represent the solutions for influencing the prognostic. Exclusion of CKD subjects from the important trials dealing with ACS and improper use of the therapeutical options because of the declined kidney functioned are issues that need to be surpassed. New ongoing trials with CKD subjects and platelets reactivity studies offers new perspectives for a better clinical approach and the expected results will clarify many aspects. Full article

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

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13 pages, 1088 KiB

Open AccessArticle

Prediction Model for Tumor Budding Status Using the Radiomic Features of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Cervical Cancer

by Gun Oh Chong, Shin-Hyung Park, Shin Young Jeong, Su Jeong Kim, Nora Jee-Young Park, Yoon Hee Lee, Sang-Woo Lee, Dae Gy Hong, Ji Young Park and Hyung Soo Han

Diagnostics 2021, 11(8), 1517; https://doi.org/10.3390/diagnostics11081517 - 23 Aug 2021

Cited by 8 | Viewed by 2617

Abstract

Objective: To compare the radiomic features of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and intratumoral heterogeneity according to tumor budding (TB) status and to develop a prediction model for the TB status using the radiomic feature of ¹⁸F-FDG [...] Read more.

Objective: To compare the radiomic features of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and intratumoral heterogeneity according to tumor budding (TB) status and to develop a prediction model for the TB status using the radiomic feature of ¹⁸F-FDG PET/CT in patients with cervical cancer. Materials and Methods: Seventy-six patients with cervical cancer who underwent radical hysterectomy and preoperative ¹⁸F-FDG PET/CT were included. We assessed the status of intratumoral budding (ITP) and peritumoral budding (PTB) in all available hematoxylin and eosin-stained specimens. Three conventional metabolic parameters and fifty-nine features were extracted and analyzed. Univariate analysis was used to identify significant metabolic parameters and radiomic findings for TB status. The prediction model for TB status was built using 3 machine learning classifiers (random forest, support vector machine, and neural network). Results: Univariate analysis led to the identification of 2 significant metabolic parameters and 12 significant radiomic features according to intratumoral budding (ITB) status. Among these parameters, following multivariate analysis for the ITB status, only compacity remained significant (odds ratio, 5.0047; 95% confidence interval, 1.1636–21.5253; p = 0.0305). Two conventional metabolic parameters and 25 radiomic features were selected by the Lasso regularization, and the prediction model for the ITB status had a mean area under the curve of 0.762 in the test dataset. Conclusion: Radiomic features of ¹⁸F-FDG PET/CT were associated with the ITB status. The prediction model using radiomic features successfully predicted the TB status in patients with cervical cancer. The prediction models for the ITB status may contribute to personalized medicine in the management of patients with cervical cancer. Full article

(This article belongs to the Special Issue Classification Systems, Neoadjuvant Setting and Prognostic Factors in Cervical Cancer)

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13 pages, 1151 KiB

Open AccessArticle

Stability of OCT and OCTA in the Intensive Therapy Unit Setting

by Ella F. Courtie, Aditya U. Kale, Benjamin T. K. Hui, Xiaoxuan Liu, Nicholas I. Capewell, Jonathan R. B. Bishop, Tony Whitehouse, Tonny Veenith, Ann Logan, Alastair K. Denniston and Richard J. Blanch

Diagnostics 2021, 11(8), 1516; https://doi.org/10.3390/diagnostics11081516 - 23 Aug 2021

Cited by 6 | Viewed by 2584

Abstract

To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood [...] Read more.

To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24–48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients. Full article

(This article belongs to the Special Issue Optical Coherence Tomography Angiography (OCTA) as a New Diagnostic Tool in Ocular and Systemic Diseases)

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14 pages, 9321 KiB

Open AccessArticle

Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy

by Shota Shimizu, Shinri Sato, Hiroko Taniguchi, Eisuke Shimizu, Jingliang He, Shunsuke Hayashi, Kazuno Negishi, Yoko Ogawa and Shigeto Shimmura

Diagnostics 2021, 11(8), 1515; https://doi.org/10.3390/diagnostics11081515 - 23 Aug 2021

Cited by 10 | Viewed by 3775

Abstract

Graft-versus-host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT), and ocular GVHD can cause severe dry eye disease that can lead to visual impairment. Epithelial damage, vascular invasion, corneal fibrosis, and corneal perforation may occur in severe cases. It [...] Read more.

Graft-versus-host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT), and ocular GVHD can cause severe dry eye disease that can lead to visual impairment. Epithelial damage, vascular invasion, corneal fibrosis, and corneal perforation may occur in severe cases. It is generally accepted that inflammatory cells such as dendritic cells and T cells contribute to this pathological condition. However, it is still unknown what pathological condition occurs on the ocular surface after HSCT, and when. We therefore observed the dynamics of inflammatory cells in the cornea of chronic GVHD (cGVHD) model mice from 1 to 4 weeks after bone marrow transplantation (BMT) by in vivo confocal microscopy (IVCM) and considered the relationship with the pathophysiology of ocular GVHD (tear volume, corneal epithelial damage). In the allogeneic group, neovascularization occurred in all eyes at 1 week after BMT, although almost all vessels disappeared at 2 weeks after BMT. In addition, we revealed that infiltration of globular cells, and tortuosity and branching of nerves in the cornea occurred in both cGVHD mice and human cGVHD patients. Thus, we consider that cGVHD mouse model study by IVCM reproduces the state of ocular GVHD and may contribute to elucidating the pathological mechanism for ocular GVHD. Full article

(This article belongs to the Special Issue Anterior-Segment Optical Coherence Tomography as a Diagnostics Tool)

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Cornea-specific in vivo laser confocal microscopy for mouse: (a) Heidelberg Retina Tomograph 2 Rostock Cornea Module (HRT2-RCM); (b) Mouse fixing device. Full article ">Figure 2
Time course in in vivo confocal microscopy (IVCM) images of cornea of the syngeneic group and allogeneic group: Upper side: (a–d) Representative IVCM images of the syngeneic group every week from 1 to 4 weeks; Lower side: (e–h) Representative IVCM images of the allogeneic group from 1 to 4 weeks, (e) Neovascularization (red circle area), (f–h) Activation of keratocytes (yellow circle area). Scale bar = 500 µm. Full article ">Figure 3
The number of cells in a circle with a diameter of 1000 µm from the center of the cornea in syngeneic group and allogeneic group: (a) The number of dendritic cells of syngeneic group and allogeneic group from 1 to 4 weeks after bone marrow transplantation (BMT); (b) The number of globular cells of syngeneic group and allogeneic group from 1 to 4 weeks after bone marrow transplantation. Data are presented as mean ± SEM. * p < 0.05, unpaired Student’s t-test. (n = 3 per group). Full article ">Figure 4
Representative in vivo confocal microscopic corneal images in mice: (a) neovascularization with moving blood cells in the allogeneic group 1 week after bone marrow transplantation (BMT) (arrowhead) and <a href="#app1-diagnostics-11-01515" class="html-app">Supplementary Video S1</a>; (b) dendritic cells with typical branching dendrites in the syngeneic group 3 weeks after bone marrow transplantation (BMT) (arrowhead); (c) small and globular cells in the allogeneic group 4 weeks after BMT (arrowhead); (d) activation of keratocyte in the allogeneic group 4 weeks after BMT; (e) nerve fibers with no abnormality in syngeneic group 4 weeks after BMT (arrowhead); (f) nerve fibers with tortuosity and branching in allogeneic group 4 weeks after BMT (arrowhead). Scale bar = 50 µm. Full article ">Figure 5
Serial changes in cornea of the syngeneic group and allogeneic group: (a) Representative images of corneal fluorescein staining and corneal erosion (arrowhead) Scale bar = 500 µm; (b) Corneal fluorescein staining score; (c) Tear volume. (n = 12 per group, 1week after BMT; n = 9 per group, 2 weeks after BMT; n = 6 per group, 3 weeks after BMT; n = 3 per group, 4 weeks after BMT). Data are presented as mean ± SEM. * p < 0.05, Mann-Whitney U Test. Full article ">Figure 6
Hematoxylin & Eosin staining of cornea from the syngeneic and allogeneic mouse model: (a,b) Syngeneic group at 3 and 4 weeks after bone marrow transplantation; (c,d) Allogeneic group at 3 and at 4 weeks after bone marrow transplantation (black arrowhead, globular cells; black arrow, keratocytes; red arrow, epithelial erosion; *, abnormal regeneration of epithelia). Scale bar = 100 µm. Full article ">Figure 7
Mallory staining (blue) of lacrimal glands indicates fibrotic areas in the syngeneic and allogeneic mouse model: (a,b) Syngeneic group at 3 and 4 weeks after bone marrow transplantation; (c,d) Allogeneic group at 3 and at 4 weeks after bone marrow transplantation. Scale bar = 100 µm. Full article ">Figure 8
Representative IVCM images of cornea in HSCT recipients without GVHD (a) and with GVHD (b,c): (a) nerve fibers with no abnormality in HSCT recipients without GVHD (arrowhead); (b) nerve fibers with tortuosity and branching in HSCT recipients with GVHD (arrowhead); (c) small and globular cells in HSCT recipients with GVHD (arrowhead). Scale bar = 50 µm. Full article ">

11 pages, 473 KiB

Open AccessArticle

Shortening the Time of the Identification and Antimicrobial Susceptibility Testing on Positive Blood Cultures with MALDI-TOF MS

by Ya-Wen Tsai, Ting-Chia Lin, Hsiu-Yin Chou, Huei-Ya Hung, Che-Kim Tan, Li-Ching Wu, I-Jung Feng and Yow-Ling Shiue

Diagnostics 2021, 11(8), 1514; https://doi.org/10.3390/diagnostics11081514 - 23 Aug 2021

Cited by 10 | Viewed by 3082

Abstract

The current processes used in clinical microbiology laboratories take ~24 h for incubation to identify the bacteria after the blood culture has been confirmed as positive and fa further ~24 h to report the results of antimicrobial susceptibility tests (ASTs). Patients with suspected [...] Read more.

The current processes used in clinical microbiology laboratories take ~24 h for incubation to identify the bacteria after the blood culture has been confirmed as positive and fa further ~24 h to report the results of antimicrobial susceptibility tests (ASTs). Patients with suspected bloodstream infection are treated with empiric broad-spectrum antibiotics but delayed targeted antimicrobial therapy. This study aimed to develop a method with a significantly shortened turnaround time for clinical application by identifying the optimal incubation period of a subculture. A total of 188 positive blood culture samples obtained from Nov. 2019 to Aug. 2020 were included. Compared to the conventional 24-h incubation for bacterial identification, our approach achieved 96.1% and 97.4% identification accuracy after shortening the incubation time to 4.5 and 3.5 h for gram-positive (GP) and gram-negative (GN) bacterial samples, respectively. Samples from short-term incubation without any intermediate step or process were directly subjected to analysis with the Phoenix M50 AST. Compared to the conventional disk diffusion AST, the category agreements for GP (excluding Streptococcus spp.), Streptococcus spp., and GN bacterial samples were 91.8%, 97.5%, and 92.7%, respectively. Our approach significantly reduced the average turnaround time from 48 h to 28 h for reporting bacterial identity and decreased average AST from 72 h to 50.3 h compared to the conventional methods. Accordingly, this approach allows a physician to prescribe the appropriate antibiotic(s) ~21.7 h earlier, thereby improving patient outcomes. Full article

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

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17 pages, 3245 KiB

Open AccessArticle

IVUS Longitudinal and Axial Registration for Atherosclerosis Progression Evaluation

by Nikos Tsiknakis, Constantinos Spanakis, Panagiota Tsompou, Georgia Karanasiou, Gianna Karanasiou, Antonis Sakellarios, George Rigas, Savvas Kyriakidis, Michael Papafaklis, Sotirios Nikopoulos, Frank Gijsen, Lampros Michalis, Dimitrios I. Fotiadis and Kostas Marias

Diagnostics 2021, 11(8), 1513; https://doi.org/10.3390/diagnostics11081513 - 22 Aug 2021

Cited by 3 | Viewed by 2889

Abstract

Intravascular ultrasound (IVUS) imaging offers accurate cross-sectional vessel information. To this end, registering temporal IVUS pullbacks acquired at two time points can assist the clinicians to accurately assess pathophysiological changes in the vessels, disease progression and the effect of the treatment intervention. In [...] Read more.

Intravascular ultrasound (IVUS) imaging offers accurate cross-sectional vessel information. To this end, registering temporal IVUS pullbacks acquired at two time points can assist the clinicians to accurately assess pathophysiological changes in the vessels, disease progression and the effect of the treatment intervention. In this paper, we present a novel two-stage registration framework for aligning pairs of longitudinal and axial IVUS pullbacks. Initially, we use a Dynamic Time Warping (DTW)-based algorithm to align the pullbacks in a temporal fashion. Subsequently, an intensity-based registration method, that utilizes a variant of the Harmony Search optimizer to register each matched pair of the pullbacks by maximizing their Mutual Information, is applied. The presented method is fully automated and only required two single global image-based measurements, unlike other methods that require extraction of morphology-based features. The data used includes 42 synthetically generated pullback pairs, achieving an alignment error of

0.1853

frames per pullback, a rotation error

0.93 °

and a translation error of

0.0161

mm. In addition, it was also tested on 11 baseline and follow-up, and 10 baseline and post-stent deployment real IVUS pullback pairs from two clinical centres, achieving an alignment error of

4.3 \pm 3.9

for the longitudinal registration, and a distance and a rotational error of

0.56 \pm 0.323

mm and

12.4 ° \pm 10.5 °

, respectively, for the axial registration. Although the performance of the proposed method does not match that of the state-of-the-art, our method relies on computationally lighter steps for its computations, which is crucial in real-time applications. On the other hand, the proposed method performs even or better that the state-of-the-art when considering the axial registration. The results indicate that the proposed method can support clinical decision making and diagnosis based on sequential imaging examinations. Full article

(This article belongs to the Special Issue Trends and Novelties in Cardiovascular Imaging)

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Sagittal views of an IVUS pullback prior to the sub-sampling of the frames corresponding to the end-diastolic cardiac phase. Full article ">Figure 2
Pre stent IVUS series (left) and post stent IVUS series (right). It is obvious that the two pullbacks differ in length, due to them either having different starting and ending points or some regions of the vessel having been captured multiple times. Full article ">Figure 3
IVUS pullbacks registration pipeline. Full article ">Figure 4
Two corresponding pairs of annotated frames based on the presence of a bifurcation (a,b) and calcification (c,d), which are highlighted with a red box in the images. Full article ">Figure 5
Example of the synthetic data. Blue line is the reference pullback, orange line is the synthetic pullback and green lines indicate the correspondences. (a) Original pullbacks with original 1-1 correspondences, (b) after applying overlapping distortion, (c) after repetition of some frames. Full article ">Figure 6
Boxplots of Mutual Information (MI) similarity metric across patients at all registration stages. Full article ">Figure 7
Longitudinal registration outcome for patient 6. Full article ">Figure 8
Longitudinal registration outcome for patient 18. Full article ">Figure 9
Sagittal vessel view corresponding to the (a) unregistered pullbacks (b) longitudinally registered pullbacks of patient 3. The left image of each subfigure corresponds to the pre-stent deployment pullback, and the right one to the post-stent deployment pullback. The red circles indicate the corresponding parts of the vesels. Full article ">Figure 10
The alignment of a bifurcation can be observed under the marked area. (a) a frame from the first pullback of patient 6, (b) its corresponding frame from the second pullback of patient 6, (c) the axially (2D) registered frame from <a href="#diagnostics-11-01513-f010" class="html-fig">Figure 10</a>b with respect to <a href="#diagnostics-11-01513-f010" class="html-fig">Figure 10</a>a. Full article ">Figure 11
The alignment of the landmarks can be observed under the marked areas. (a) a frame from the first pullback of patient 18, (b) its corresponding frame from the second pullback of patient 18, (c) the axially (2D) registered frame from <a href="#diagnostics-11-01513-f011" class="html-fig">Figure 11</a>b with respect to <a href="#diagnostics-11-01513-f011" class="html-fig">Figure 11</a>a. Full article ">Figure 12
The alignment of the landmarks can be observed under the marked areas. (a) a frame from the first pullback of patient 3, (b) its corresponding frame from the second pullback of patient 3, (c) the axially (2D) registered frame from <a href="#diagnostics-11-01513-f012" class="html-fig">Figure 12</a>b with respect to <a href="#diagnostics-11-01513-f012" class="html-fig">Figure 12</a>a. Full article ">

9 pages, 3484 KiB

Open AccessArticle

Visualization of Forward Light Scatter in Opacified Intraocular Lenses and Straylight Assessment

by Hyeck-Soo Son, Grzegorz Łabuz, Ramin Khoramnia, Timur M. Yildirim, Chul Young Choi, Michael C. Knorz and Gerd U. Auffarth

Diagnostics 2021, 11(8), 1512; https://doi.org/10.3390/diagnostics11081512 - 22 Aug 2021

Cited by 9 | Viewed by 2744

Abstract

Background: Qualitative visualization of forward light scatter and quantitative straylight measurement of intraocular lenses (IOLs). Methods: We analyzed two calcified IOL-explants, the Euromaxx ALI313Y (Argonoptics GmbH) and the LS-312 MF30 (Oculentis BV), one IOL with artificially induced glistenings (PC-60AD, Hoya), and one control [...] Read more.

Background: Qualitative visualization of forward light scatter and quantitative straylight measurement of intraocular lenses (IOLs). Methods: We analyzed two calcified IOL-explants, the Euromaxx ALI313Y (Argonoptics GmbH) and the LS-312 MF30 (Oculentis BV), one IOL with artificially induced glistenings (PC-60AD, Hoya), and one control (CT Asphina 409MP, Carl Zeiss Meditec AG) free of any opacification. Analysis included light microscopy, qualitative light scatter visualization using ray propagation imaging technique, and quantitative straylight measurement using C-Quant (Oculus). Results: More light scattering effect—visible as increased light intensity outside the IOL’s main focus—was evident in all opacified IOLs than the control. The highest straylight levels were observed in the Euromaxx (289.71 deg²/sr), which showed extensive granular deposits throughout its optic, followed by the MF30 (78.58 deg²/sr), which only showed opacification in its center. The glistenings-IOL demonstrated numerous microvacuoles within the optic and had straylight levels of 22.6 deg²/sr, while the control showed the lowest straylight levels (1.7 deg²/sr). Conclusions: Ray propagation imaging technique allowed qualitative assessment of off-axis veils of light that result from increased forward light scattering. Straylight was increased in all opacified lenses compared to the clear control lens. The IOL opacifications are significant sources of glare. Full article

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

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Experimental set-up for direct visualization of the light scattering effects. (A) Schematic illustration, (B) in vitro optical bench set-up. To elaborate, 1 = monochromatic green laser light source (532 nm); 2 = model cornea; 3 = intraocular lens holder; 4 = surgical microscope with an integrated digital camera; and 5 = water bath containing 0.01% fluorescein solution. Full article ">Figure 2
Gross microscopic images of the studied IOLs. (A–D) Overview images, (E–H) images taken with 4-fold magnification, (I–L) images taken with 40-fold magnification. Full article ">Figure 3
Ray propagation (A) and light scattering (B) of the control IOL. The arrow indicates the focal point of the studied IOL, while the arrowhead points to the scatter light made visible as background haze when the ray propagation image is converted to a log image. Full article ">Figure 4
Ray propagation (A) and light scattering (B) of the glistenings-IOL. The arrow indicates its focal point, while the arrowhead points to its extent of scatter light. Full article ">Figure 5
Ray propagation and light scattering of the calcified LS-312 MF30 (A,B) and Euromaxx (C,D) IOL-explants. The arrows indicate the focal point, while the arrowheads point to the scatter light. Full article ">Figure 6
Straylight parameter of the studied IOLs measured by the C-Quant device. The results are compared to the normative values of a 20-year-old crystalline lens, 70-year-old crystalline lens, and a cataract lens [<a href="#B23-diagnostics-11-01512" class="html-bibr">23</a>,<a href="#B24-diagnostics-11-01512" class="html-bibr">24</a>]. Full article ">

10 pages, 657 KiB

Open AccessArticle

Mouth Washing Impaired SARS-CoV-2 Detection in Saliva

by Monique Melo Costa, Nicolas Benoit, Hervé Tissot-Dupont, Matthieu Million, Bruno Pradines, Samuel Granjeaud and Lionel Almeras

Diagnostics 2021, 11(8), 1509; https://doi.org/10.3390/diagnostics11081509 - 22 Aug 2021

Cited by 5 | Viewed by 2829

Abstract

Background: A previous study demonstrated the performance of the Salivette^® (SARSTEDT, Numbrecht, Germany) as a homogeneous saliva collection system to diagnose COVID-19 by RT-qPCR, notably for symptomatic and asymptomatic patients. However, for convalescent patients, the corroboration of molecular detection of SARS-CoV-2 in [...] Read more.

Background: A previous study demonstrated the performance of the Salivette^® (SARSTEDT, Numbrecht, Germany) as a homogeneous saliva collection system to diagnose COVID-19 by RT-qPCR, notably for symptomatic and asymptomatic patients. However, for convalescent patients, the corroboration of molecular detection of SARS-CoV-2 in paired nasopharyngeal swabs (NPS) and saliva samples was unsatisfactory. Objectives: The aim of the present work was to assess the concordance level of SARS-CoV-2 detection between paired sampling of NPSs and saliva collected with Salivette^® at two time points, with ten days of interval. Results: A total of 319 paired samples from 145 outpatients (OP) and 51 healthcare workers (HW) were collected. Unfortunately, at day ten, 73 individuals were lost to follow-up, explaining some kinetic missing data. Due to significant waiting rates at hospitals, most of the patients ate and/or drank while waiting for their turn. Consequently, mouth washing was systematically proposed prior to saliva collection. None of the HW were diagnosed as SARS-CoV-2 positive using NPS or saliva specimens at both time points (n = 95) by RT-qPCR. The virus was detected in 56.3% (n = 126/224) of the NPS samples from OP, but solely 26.8% (n = 60/224) of the paired saliva specimens. The detection of the internal cellular control, the human RNase P, in more than 98% of the saliva samples, underlined that the low sensitivity of saliva specimens (45.2%) for SARS-CoV-2 detection was not attributed to an improper saliva sample storing or RNA extraction. Conclusions: This work revealed that mouth washing decreased viral load of buccal cavity conducting to impairment of SARS-CoV-2 detection. Viral loads in saliva neo-produced appeared insufficient for molecular detection of SARS-CoV-2. At the time when saliva tests could be a rapid, simple and non-invasive strategy to assess large scale schoolchildren in France, the determination of the performance of saliva collection becomes imperative to standardize procedures. Full article

(This article belongs to the Special Issue SARS-CoV-2 Identification by Diagnostic/Medical Laboratory: Methods, Statistics, Interesting Cases)

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Comparison of Ct values from NPSs and saliva samples. (A) Ct values from all SARS-CoV-2 positive NPSs (n = 126) and saliva (n = 60) samples were compared using a Mann-Whitney U test (*** p < 0.0001). (B) Paired SARS-CoV-2 positive samples (n = 57), represented by the connecting lines, were compared by a Wilcoxon test (*** p < 0.0001). (C) SARS-CoV-2 Ct values from positive NPS samples found positives (n = 57) or negatives (n = 69) in saliva specimens were compared by a Mann-Whitney U test (*** p < 0.0001). (D) Comparison of human RNase P (HRNP) Ct values from saliva samples between outpatients (OP) collected at D0 (n = 145), D10 (n = 79) and healthcare workers (HW) collected at D0 (n = 51), D10 (n = 44) (p > 0.05, Kruskal-Wallis test). (E) Comparison of human RNase P Ct values between saliva samples with (n = 25) and without (n = 294) water addition (*** p < 0.0001, Mann-Whitney U test). (F) Comparison of human RNase P Ct values between saliva samples collected with Salivettes without water addition, with (n = 265, present work) and without (n = 289, previous study [<a href="#B15-diagnostics-11-01509" class="html-bibr">15</a>]) mouth washing before sampling (*** p < 0.0001, Mann-Whitney U test). Uniquely significant paired comparisons were indicated. Bars represent the median and 95% CI. Full article ">

15 pages, 1597 KiB

Open AccessReview

A 10-Year Retrospective Review of Prenatal Applications, Current Challenges and Future Prospects of Three-Dimensional Sonoangiography

by Tuangsit Wataganara, Thanapa Rekhawasin, Nalat Sompagdee, Sommai Viboonchart, Nisarat Phithakwatchara and Katika Nawapun

Diagnostics 2021, 11(8), 1511; https://doi.org/10.3390/diagnostics11081511 - 21 Aug 2021

Cited by 5 | Viewed by 2927

Abstract

Realistic reconstruction of angioarchitecture within the morphological landmark with three-dimensional sonoangiography (three-dimensional power Doppler; 3D PD) may augment standard prenatal ultrasound and Doppler assessments. This study aimed to (a) present a technical overview, (b) determine additional advantages, (c) identify current challenges, and (d) [...] Read more.

Realistic reconstruction of angioarchitecture within the morphological landmark with three-dimensional sonoangiography (three-dimensional power Doppler; 3D PD) may augment standard prenatal ultrasound and Doppler assessments. This study aimed to (a) present a technical overview, (b) determine additional advantages, (c) identify current challenges, and (d) predict trajectories of 3D PD for prenatal assessments. PubMed and Scopus databases for the last decade were searched. Although 307 publications addressed our objectives, their heterogeneity was too broad for statistical analyses. Important findings are therefore presented in descriptive format and supplemented with the authors’ 3D PD images. Acquisition, analysis, and display techniques need to be personalized to improve the quality of flow-volume data. While 3D PD indices of the first-trimester placenta may improve the prediction of preeclampsia, research is needed to standardize the measurement protocol. In highly experienced hands, the unique 3D PD findings improve the diagnostic accuracy of placenta accreta spectrum. A lack of quality assurance is the central challenge to incorporating 3D PD in prenatal care. Machine learning may broaden clinical translations of prenatal 3D PD. Due to its operator dependency, 3D PD has low reproducibility. Until standardization and quality assurance protocols are established, its use as a stand-alone clinical or research tool cannot be recommended. Full article

(This article belongs to the Special Issue Application of 3D-Imaging in Diagnosis)

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12 pages, 20546 KiB

Open AccessArticle

Morphological and Morphometric Characteristics of Anterior Maxilla Accessory Canals and Relationship with Nasopalatine Canal Type—A CBCT Study

by Milica Vasiljevic, Pavle Milanovic, Nemanja Jovicic, Miroslav Vasovic, Dragan Milovanovic, Radisa Vojinovic, Dragica Selakovic and Gvozden Rosic

Diagnostics 2021, 11(8), 1510; https://doi.org/10.3390/diagnostics11081510 - 21 Aug 2021

Cited by 9 | Viewed by 3067

Abstract

This study aimed to evaluate principal morphological and morphometric characteristics of accessory canals (ACs) of the anterior maxilla, as well as to analyze the relationship with nasopalatine canal (NPC) type. The results of our study showed that ACs were observed in almost 50% [...] Read more.

This study aimed to evaluate principal morphological and morphometric characteristics of accessory canals (ACs) of the anterior maxilla, as well as to analyze the relationship with nasopalatine canal (NPC) type. The results of our study showed that ACs were observed in almost 50% of participants. They were mostly presented bilaterally and in a curved shape, with a palatal foramen position. The morphometric characteristics of ACs were significantly influenced by NPC type. NPC type had the strongest impact on the distance between the NPC and AC, as well as on the distance between the AC and the facial aspect of buccal bone wall, in inferior parts of the alveolar ridge. On the other hand, the distance between the AC and central incisors was not significantly influenced by NPC shape in the lower region of the anterior maxilla. However, the participants with the banana-type of the NPC expressed the reduction in distance from the AC to the central incisor at the upper part in comparison with the subjects with the cylindrical-type of the NPC. On the basis of the results of this study, the simultaneous estimation of ACs and the NPC seems reasonable, as this approach may be useful in the prevention of complications which could occur during implant surgery interventions. Full article

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

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CBCT slices and landmarks of interest. Sagittal cross-section—sagittal CBCT slice (left, upper); slice with marked field of interest (left, bellow); selected landmarks for analyses (right)—(A) the distance between the buccal border of incisive foramen and facial aspect of the buccal bone wall, (B) the distance between the buccal wall of the nasopalatine canal and facial aspect of the buccal bone wall using a horizontal line from the palatal border of the incisive foramen, (C) the distance between the buccal border at the midpoint level of NPC length and facial aspect of the buccal bone wall, (D) the distance between the buccal border of nasal foramen and facial aspect of the buccal bone wall; Axial cross-section—axial CBCT slice (right); (a) the diameter of AC, (b) the distance between AC and NPC, (c) the distance between AC and facial aspect of the buccal bone wall, (d) the distance between AC and central incisor root. Full article ">Figure 2
CBCT slices and marks of interest. Accessory canal shapes at the coronal cross-section (upper); red marks define ACs shapes at the coronal cross-section (below). Full article ">Figure 3
Maximal diameter of accessory canal at different levels of anterior maxilla according to NPC shape. Values are expressed as the mean ± SEM. Full article ">Figure 4
The distance of accessory canal from NPC at different levels of anterior maxilla according to NPC shape. Values are expressed as the mean ± SEM. * denotes a significant difference of p < 0.05, ** denotes a significant difference of p < 0.01. Full article ">Figure 5
The distance of accessory canal from facial aspect of the buccal bone wall at different levels of anterior maxilla according to NPC shape. Values are expressed as the mean ± SEM. * denotes a significant difference of p < 0.05, ** denotes a significant difference of p < 0.01. Full article ">Figure 6
The distance of accessory canal from central incisor at different levels of anterior maxilla according to NPC shape. Values are expressed as the mean ± SEM. ** denotes a significant difference of p < 0.01. Full article ">

20 pages, 4696 KiB

Open AccessArticle

Deep Learning Analysis of In Vivo Hyperspectral Images for Automated Intraoperative Nerve Detection

by Manuel Barberio, Toby Collins, Valentin Bencteux, Richard Nkusi, Eric Felli, Massimo Giuseppe Viola, Jacques Marescaux, Alexandre Hostettler and Michele Diana

Diagnostics 2021, 11(8), 1508; https://doi.org/10.3390/diagnostics11081508 - 21 Aug 2021

Cited by 20 | Viewed by 3651

Abstract

Nerves are critical structures that may be difficult to recognize during surgery. Inadvertent nerve injuries can have catastrophic consequences for the patient and lead to life-long pain and a reduced quality of life. Hyperspectral imaging (HSI) is a non-invasive technique combining photography with [...] Read more.

Nerves are critical structures that may be difficult to recognize during surgery. Inadvertent nerve injuries can have catastrophic consequences for the patient and lead to life-long pain and a reduced quality of life. Hyperspectral imaging (HSI) is a non-invasive technique combining photography with spectroscopy, allowing non-invasive intraoperative biological tissue property quantification. We show, for the first time, that HSI combined with deep learning allows nerves and other tissue types to be automatically recognized in in vivo hyperspectral images. An animal model was used, and eight anesthetized pigs underwent neck midline incisions, exposing several structures (nerve, artery, vein, muscle, fat, skin). State-of-the-art machine learning models were trained to recognize these tissue types in HSI data. The best model was a convolutional neural network (CNN), achieving an overall average sensitivity of 0.91 and a specificity of 1.0, validated with leave-one-patient-out cross-validation. For the nerve, the CNN achieved an average sensitivity of 0.76 and a specificity of 0.99. In conclusion, HSI combined with a CNN model is suitable for in vivo nerve recognition. Full article

(This article belongs to the Section Biomedical Optics)

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12 pages, 968 KiB

Open AccessArticle

Watch and Wait Approach for Rectal Cancer Following Neoadjuvant Treatment: The Experience of a High Volume Cancer Center

by Daniela Rega, Vincenza Granata, Carmela Romano, Valentina D’Angelo, Ugo Pace, Roberta Fusco, Carmela Cervone, Vincenzo Ravo, Fabiana Tatangelo, Antonio Avallone, Antonella Petrillo and Paolo Delrio

Diagnostics 2021, 11(8), 1507; https://doi.org/10.3390/diagnostics11081507 - 21 Aug 2021

Cited by 13 | Viewed by 4015

Abstract

Multimodal treatments for rectal cancer, along with significant research on predictors to response to therapy, have led to more conservative surgical strategies. We describe our experience of the rectal sparing approach in rectal cancer patients with clinical complete response (cCR) after neoadjuvant treatment. [...] Read more.

Multimodal treatments for rectal cancer, along with significant research on predictors to response to therapy, have led to more conservative surgical strategies. We describe our experience of the rectal sparing approach in rectal cancer patients with clinical complete response (cCR) after neoadjuvant treatment. We also specifically highlight our clinical and imaging criteria to select patients for the watch and wait strategy (w&w). Data came from 39 out of 670 patients treated for locally advanced rectal cancer between January 2016 until February 2020. The selection criteria were a clinical complete response after neoadjuvant chemotherapy managed with a watch and wait (w&w) strategy. A strict follow-up period was adopted in these selected patients and follow-ups were performed every three months during the first two years and every six months after that. The median follow-up time was 28 months. Six patients had a local recurrence (15.3%); all were salvageable by total mesorectal excision (TME). Five patients had a distant metastasis (12.8%). There was no local unsalvageable disease after w&w strategy. The rectal sparing approach in patients with clinical complete response after neoadjuvant treatment is the best possible treatment and is appropriate to analyze from this perspective. The watch and wait approach after neoadjuvant treatment for rectal cancer can be successfully explored after inflexible and strict patient selection. Full article

(This article belongs to the Special Issue Diagnosis and Management of Rectal Cancer)

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13 pages, 1263 KiB

Open AccessArticle

Development and Evaluation of a Set of Spike and Receptor Binding Domain-Based Enzyme-Linked Immunosorbent Assays for SARS-CoV-2 Serological Testing

by Rosa Camacho-Sandoval, Alejandro Nieto-Patlán, Gregorio Carballo-Uicab, Alejandra Montes-Luna, María C. Jiménez-Martínez, Luis Vallejo-Castillo, Edith González-González, Hugo Iván Arrieta-Oliva, Keyla Gómez-Castellano, Omar U. Guzmán-Bringas, María Pilar Cruz-Domínguez, Gabriela Medina, Laura A. Montiel-Cervantes, Maricela Gordillo-Marín, Roberto Vázquez-Campuzano, Belem Torres-Longoria, Irma López-Martínez, Sonia M. Pérez-Tapia and Juan Carlos Almagro

Diagnostics 2021, 11(8), 1506; https://doi.org/10.3390/diagnostics11081506 - 20 Aug 2021

Cited by 11 | Viewed by 3941

Abstract

The implementation and validation of anti-SARS-CoV-2 IgG serological assays are reported in this paper. S1 and RBD proteins were used to coat ELISA plates, and several secondary antibodies served as reporters. The assays were initially validated with 50 RT-PCR positive COVID-19 sera, which [...] Read more.

The implementation and validation of anti-SARS-CoV-2 IgG serological assays are reported in this paper. S1 and RBD proteins were used to coat ELISA plates, and several secondary antibodies served as reporters. The assays were initially validated with 50 RT-PCR positive COVID-19 sera, which showed high IgG titers of mainly IgG1 isotype, followed by IgG3. Low or no IgG2 and IgG4 titers were detected. Then, the RBD/IgG assay was further validated with 887 serum samples from RT-PCR positive COVID-19 individuals collected at different times, including 7, 14, 21, and 40 days after the onset of symptoms. Most of the sera were IgG positive at day 40, with seroconversion happening after 14–21 days. A third party conducted an additional performance test of the RBD/IgG assay with 406 sera, including 149 RT-PCR positive COVID-19 samples, 229 RT-PCR negative COVID-19 individuals, and 28 sera from individuals with other viral infections not related to SARS-CoV-2. The sensitivity of the assay was 99.33%, with a specificity of 97.82%. All the sera collected from individuals with infectious diseases other than COVID-19 were negative. Given the robustness of this RBD/IgG assay, it received approval from the sanitary authority in Mexico (COFEPRIS) for production and commercialization under the name UDISTEST-V2G^®. Full article

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

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Characterization of the RBD protein. The RBD protein was expressed in HEK 293 cell cultures and purified on a HisTrap™ Nickel column; two fractions were obtained. (A) Native SEC analysis evinced that Fraction 1 (RBD F1; black line) was mainly composed of a ~100 kDa protein and Fraction 2 (RBD F2; blue line) by a ~30 kDa protein, which may correspond to the trimer and monomer of the RBD protein, respectively. (B) Fraction 2 also exhibits the main band at ~30 kDa when analyzed in denaturing SDS-PAGE using two reducing agents (BME and DTT). Fraction 2 was used for the rest of the work. Full article ">Figure 2
Absorbance values of the 15 negative and 15 positive COVID-19 samples were used to standardize the (A) S1- and (B) RBD-based IgG assays. Each absorbance value in the plots is the average of six measurements: two sets of triplicates, with one set of triplicates performed one day, and another set of triplicates performed on a different day. Full article ">Figure 3
(A) S1 and (B) RBD test results of the 50 serum samples. Three dilutions (1:100, 1:1000, and 1:3000) per serum sample were assayed. Each data point is the average of duplicates. Full article ">Figure 4
IgG isotyping using (A) S1- and (B) RBD-based tests. IgG: total IgG. Red squares represent negative controls. All serum samples were assayed at a 1:100 dilution. Full article ">Figure 5
IgG seroconversion of COVID-19 RT-PCR positive patients evaluated with UDITEST-V2G®. Serum samples from COVID-19 RT-PCR positive patients were evaluated on day 7, 14, 21, and 40 after the onset of symptoms. Positive and negative IgG samples are shown. **** p < 0.0001 student t-test. Full article ">

10 pages, 6951 KiB

Open AccessArticle

Magnetic Resonance Detects Structural Heart Disease in Patients with Frequent Ventricular Ectopy and Normal Echocardiographic Findings

by Raffaele Scorza, Anders Jansson, Peder Sörensson, Mårten Rosenqvist and Viveka Frykman

Diagnostics 2021, 11(8), 1505; https://doi.org/10.3390/diagnostics11081505 - 20 Aug 2021

Cited by 4 | Viewed by 2953

Abstract

The prognosis of patients with ventricular ectopy and a normal heart, as evaluated by echocardiography, is virtually unknown. Cardiac magnetic resonance (CMR) can detect focal ventricular anomalies that could act as a possible site of origin for premature ventricular contractions (PVCs). The aim [...] Read more.

The prognosis of patients with ventricular ectopy and a normal heart, as evaluated by echocardiography, is virtually unknown. Cardiac magnetic resonance (CMR) can detect focal ventricular anomalies that could act as a possible site of origin for premature ventricular contractions (PVCs). The aim of this study was to investigate the presence of cardiac anomalies in patients with normal findings at echocardiogram. Methods: Fifty-one consecutive patients (23 women, 28 men, mean age 59 years) with very high PVC burden (>10,000 PVC/day) and normal findings at standard echocardiography and exercise test were examined with CMR. The outcome was pathologic findings, defined as impaired ejection fraction, regional wall motion abnormalities, abnormal ventricular volume, myocardial edema and fibrosis. Results: Sixteen out of 51 patients (32%) had structural ventricular abnormalities at CMR. In five patients CMR showed impairment of the left ventricular and/or right ventricular systolic function, and six patients had a dilated left and/or right ventricle. Regional wall motion abnormalities were seen in six patients and fibrosis in four. No patient had CMR signs of edema or met CMR criteria for arrhythmogenic right ventricular cardiomyopathy. Five patients had extra-ventricular findings (enlarged atria in three cases, enlarged thoracic aorta in one case and pericardial effusion in one case). Conclusions: In this study 16 out of 51 patients with a high PVC burden and normal findings at echocardiography showed signs of pathology in the ventricles with CMR. These findings indicate that CMR should be considered in evaluating patients with a high PVC burden and a normal standard investigation. Full article

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

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20 pages, 2885 KiB

Open AccessArticle

The Diagnostic Usefulness of ¹³¹I-SPECT/CT at Both Radioiodine Ablation and during Long-Term Follow-Up in Patients Thyroidectomized for Differentiated Thyroid Carcinoma: Analysis of Tissue Risk Factors Ascertained at Surgery and Correlated with Metastasis Appearance

by Angela Spanu, Susanna Nuvoli, Andrea Marongiu, Ilaria Gelo, Luciana Mele, Andrea De Vito, Maria Rondini and Giuseppe Madeddu

Diagnostics 2021, 11(8), 1504; https://doi.org/10.3390/diagnostics11081504 - 20 Aug 2021

Cited by 13 | Viewed by 4093

Abstract

¹³¹I Single-photon emission computerized tomography/computerized tomography (SPECT/CT) in the management of patients thyroidectomized for differentiated thyroid carcinoma (DTC) was further investigated. Retrospectively, 106 consecutive DTC patients were enrolled at the first radioiodine ablation, 24 at high risk (H), 61 at low risk [...] Read more.

¹³¹I Single-photon emission computerized tomography/computerized tomography (SPECT/CT) in the management of patients thyroidectomized for differentiated thyroid carcinoma (DTC) was further investigated. Retrospectively, 106 consecutive DTC patients were enrolled at the first radioiodine ablation, 24 at high risk (H), 61 at low risk (L) and 21 at very low risk (VL). ¹³¹I whole-body scan (WBS) and SPECT/CT were performed after therapeutic doses using a hybrid dual-head gamma camera. At ablation, SPECT/CT correctly classified 49 metastases in 17/106 patients with a significantly (p < 0.001) more elevated number than WBS which evidenced 32/49 foci in 13/17 cases. In this case, 86/106 patients could be monitored in the follow-up including 13/17 cases with metastases already at post-therapeutic scans. SPECT/CT after radioiodine diagnostic doses more correctly than WBS ascertained disease progression in 4/13 patients, stable disease in other 4/13 cases and disease improvement in the remaining 5/13 cases. Further 13/86 patients with only residues at post-therapeutic scans showed at SPECT/CT 16 neck lymph node (LN) metastases, three unclear and 13 occult at WBS. Significant involvement of some tissue risk factors with metastasis appearance was observed, such as minimal extrathyroid tumor extension and neck LN metastases. These risk factors should be carefully considered in DTC patient follow-up where ¹³¹I-SPECT/CT routinely use is suggested as a support tool of WBS. Full article

(This article belongs to the Special Issue Image-Based Diagnostics and Radiometabolic Therapy of Differentiated Thyroid Cancer)

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A 73-y-old male patient (case n. 8, <a href="#diagnostics-11-01504-t003" class="html-table">Table 3</a>), thyroidectomized for thyroid papillary carcinoma, follicular variant, tumor diameter 25 mm, at the first radioiodine ablation. 131I-WBS after a therapeutic dose, in both anterior (a) and posterior (b) views, showed one radioiodine-avid focus in left hemithorax suspected of metastasis (red arrow). Fused SPECT/CT images in coronal (c), sagittal (d) and transaxial (e) slides confirmed the focus (red arrows) specifying the anatomic site (anterior segment of the superior lobe) and characterizing it as lung metastasis, as also confirmed at CT (f). In addition, fused SPECT/CT images in coronal (g) and transaxial (h) slides evidenced another radioiodine-avid focus (green arrows) in the neck corresponding to a right paratracheal lymph node occult at WBS and classified as metastasis. Thyroglobulin levels in hypothyroidism condition: 1362 ng/mL. AbTg: Absent. Full article ">Figure 2
A 42-y-old male patient (case n. 2, <a href="#diagnostics-11-01504-t003" class="html-table">Table 3</a>), thyroidectomized for papillary carcinoma, tumor diameter 14mm, at the first radioiodine ablation. 131I-WBS after a therapeutic dose, in both anterior (a) and posterior (b) views, showed two radioiodine-avid foci of different dimension and activity in the median region of the neck (white arrows), better evidenced in anterior view and classified as tissue residues in thyroid bed; moreover, a slightly heterogeneous radioiodine uptake was ascertained in right laterocervical region classified as unclear. Fused SPECT/CT images in coronal (c), sagittal (d) and transaxial (e–g) views evidenced the aforementioned two foci (white arrows) in the thyroid bed confirming the classification as residues. SPECT/CT also identified two further circumscribed foci (red and green arrows) in right laterocervical region, whose uptakes were considered unclear by WBS, classifying these as lymph node metastases, as confirmed by CT (f–h). Thyroglobulin levels in hypothyroidism condition: 29.3 ng/mL. AbTg: absent. Full article ">Figure 3
The same patient described in <a href="#diagnostics-11-01504-f002" class="html-fig">Figure 2</a> (case n. 2, <a href="#diagnostics-11-01504-t003" class="html-table">Table 3</a>) was re-evaluated in the follow-up. WBS in both anterior (a) and posterior (b) views did not show any radioiodine avid foci to consider as residues or malignant lesions. Fused SPECT/CT images in coronal (c) and left (d) and right sagittal (e) views excluded the two malignant foci evidenced in basal condition. However, it identified three new foci, two of which in the left laterocervical region (red and yellow arrows) and another in right laterocervical region, the latter better evidenced in sagittal right view (green arrow) and confirmed by CT (f). These foci were classified as lymph node metastases in disease progression. The patient was treated again with a therapeutic dose of radioiodine. Thyroglobulin levels in hypothyroidism condition: 36 ng/mL. AbTg: absent. Full article ">Figure 4
A 60-y-old female patient (case n. 13, <a href="#diagnostics-11-01504-t004" class="html-table">Table 4</a>) submitted to total thyroidectomy for multifocal-bilateral papillary carcinoma, tumor diameter 15 mm, at the first radioiodine ablation.131I-WBS after therapeutic radioiodine dose, in both anterior (a) and posterior (b) views evidenced two radioiodine-avid foci of different activity in the median region of the neck classified as tissue residues. Fused SPECT/CT images in transaxial slides (c,d) also identified the two foci evidenced by WBS confirming residual origin. Both WBS and SPECT/CT excluded the presence of foci doubtful of malignant lesions. Thyroglobulin levels in hypothyroidism condition: 4.2 ng/mL. AbTg: absent. Full article ">Figure 5
The same female patient described in <a href="#diagnostics-11-01504-f004" class="html-fig">Figure 4</a> (case n. 13, <a href="#diagnostics-11-01504-t004" class="html-table">Table 4</a>) was also evaluated during follow-up. 131I-WBS after diagnostic dose of radioiodine in both anterior (a) and posterior (b) views did not evidence the residue foci ascertained at the exam performed after therapeutic dose and excluded the presence of other foci doubtful of malignant lesions. Fused SPECT/CT images in coronal (c), sagittal (d) and transaxial (e) slides did not evidence the two foci classified as residues at the previous exam during ablation. However, SPECT/CT identified two new foci, one in right laterocervical region (e, red arrow) and the other in right supraclavicular region (g, green arrow), both of these occult at WBS. These foci, confirmed at CT (f,h), were classified as lymph node metastases. The patient was treated with a radioiodine therapeutic dose again. Thyroglobulin levels in hypothyroidism condition: 13 ng/mL. AbTg: absent. Full article ">

11 pages, 1514 KiB

Open AccessCommunication

Active MMP-8 Quantitative Test as an Adjunctive Tool for Early Diagnosis of Periodontitis

by Marcela Hernández, Mauricio Baeza, Ismo T. Räisänen, Johanna Contreras, Taina Tervahartiala, Alejandra Chaparro, Timo Sorsa and Patricia Hernández-Ríos

Diagnostics 2021, 11(8), 1503; https://doi.org/10.3390/diagnostics11081503 - 20 Aug 2021

Cited by 20 | Viewed by 4147

Abstract

Periodontitis is a host-mediated bacterial disease that affects the tooth attachment apparatus. Metalloproteinase-8 (MMP-8), a validated biomarker, could aid in clinical diagnosis. This study aimed to evaluate the diagnostic performance of active (a) MMP-8 immunotest versus total (t) MMP-8 ELISA for quantitative real-time [...] Read more.

Periodontitis is a host-mediated bacterial disease that affects the tooth attachment apparatus. Metalloproteinase-8 (MMP-8), a validated biomarker, could aid in clinical diagnosis. This study aimed to evaluate the diagnostic performance of active (a) MMP-8 immunotest versus total (t) MMP-8 ELISA for quantitative real-time diagnosis and assessment of periodontitis severity at the site level. Gingival crevicular fluid (GCF) was sampled from 30 healthy, 42 mild, and 59 severe periodontitis sites from thirty-one volunteers. MMP-8 concentrations were determined by time-resolved immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the STATA package. Both active and total MMP-8-based methods discriminated among sites according to periodontal diagnosis and severity, with a positive correlation between the two tests (p < 0.001). (a) MMP-8 models showed the best performance in receiver operating characteristic (ROC) curves to discriminate between healthy and periodontitis sites (area under the curve [AUC] = 0.89), while (t) MMP-8 demonstrated a high diagnostic precision in the detection of mild from severe periodontitis sites (AUC ≥ 0.80). The use of (a) MMP-8 and (t) MMP-8 could represent a useful adjunctive tool for periodontitis diagnosis and severity. These results support the applicability of new point-of-care methods in the monitoring of high-risk periodontal patients. Full article

(This article belongs to the Special Issue Dental Peri-Implant Point-of-Care Tests)

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MMP-8 levels in healthy and periodontitis sites. (A1) Active and (A2) total MMP-8 levels by diagnosis. (B1) Active and (B2) total MMP-8 levels by disease periodontitis severity. (a) active; (t) total. * p < 0.0001. Full article ">Figure 2
Diagnostic potential of MMP-8 tests to identify healthy sites. Diagnostic potential of active metalloproteinase-8 (a) MMP-8, to identify healthy from periodontitis sites, crude (A1) and adjusted (A2) models; diagnostic potential of (t) MMP-8 to identify healthy from periodontitis sites, crude (B1) and adjusted (B2) models; (C) sensitivity, specificity, and cut-off points of (a) MMP-8 and (t) MMP-8 diagnostic potential to identify healthy from periodontitis sites. AUC: area under the curve. CI: confidence interval. (a) MMP-8: active matrix metalloproteinase-8; (t) MMP-8: total matrix metalloproteinase-8. Immp8: IFMA MMP-8; Emmp8: ELISA MMP-8. Full article ">Figure 3
Diagnostic potential of biomarkers to identify severe periodontitis sites. Diagnostic potential of (a) MMP-8 to identify mild from severe periodontitis sites, crude (A1) and adjusted (A2) models; diagnostic potential of (t) MMP-8 to identify mild from severe periodontitis sites, crude (B1) and adjusted (B2) models; (C) sensitivity, specificity and cut-off points of (a) MMP-8 and (t) MMP-8. AUC: area under the curve. CI: confidence interval. (a) MMP-8: active matrix metalloproteinase-8; (t) MMP-8: total matrix metalloproteinase-8. Immp8: IFMA MMP-8; Emmp8: ELISA MMP-8. Full article ">

17 pages, 2282 KiB

Open AccessArticle

A Novel System for Semiautomatic Sample Processing in Chronic Myeloid Leukaemia: Increasing Throughput without Impacting on Molecular Monitoring at Time of SARS-CoV-2 Pandemic

by Stefania Stella, Silvia Rita Vitale, Michele Massimino, Adriana Puma, Cristina Tomarchio, Maria Stella Pennisi, Elena Tirrò, Chiara Romano, Federica Martorana, Fabio Stagno, Francesco Di Raimondo and Livia Manzella

Diagnostics 2021, 11(8), 1502; https://doi.org/10.3390/diagnostics11081502 - 20 Aug 2021

Cited by 1 | Viewed by 2585

Abstract

Molecular testing of the BCR-ABL1 transcript via real-time quantitative-polymerase-chain-reaction is the most sensitive approach for monitoring the response to tyrosine-kinase-inhibitors therapy in chronic myeloid leukaemia (CML) patients. Each stage of the molecular procedure has been standardized and optimized, including the total white blood [...] Read more.

Molecular testing of the BCR-ABL1 transcript via real-time quantitative-polymerase-chain-reaction is the most sensitive approach for monitoring the response to tyrosine-kinase-inhibitors therapy in chronic myeloid leukaemia (CML) patients. Each stage of the molecular procedure has been standardized and optimized, including the total white blood cells (WBCs) and RNA isolation methods. Here, we compare the performance of our current manual protocol to a newly semiautomatic method based on the Biomek i-5 Automated Workstations integrated with the CytoFLEX Flow Cytometer, followed by the automatic QIAsymphony system to facilitate high-throughput processing samples and reduce the hands-on time and the risk associated with SARS-CoV-2. The recovery efficiency was investigated in blood samples from 100 adults with CML. We observe a 100% of concordance between the two methods, with similar total WBCs isolated (median 1.137 × 10⁶ for manual method vs. 1.076 × 10⁶ for semiautomatic system) and a comparable quality and quantity of RNA extracted (median 103 ng/μL with manual isolation kit vs. 99.95 ng/μL with the QIAsymphony system). Moreover, by stratifying patients according to their BCR-ABL1 transcript levels, we obtained similar BCR-ABL1/ABL1^IS values and ABL1 copies, and matched samples were assigned to the same group of molecular response. We conclude that this newly semiautomatic workflow has a performance comparable to our more laborious standard manual, which can be replaced, particularly when specimens from patients with suspected or confirmed SARS-CoV-2 infection need to be processed. Full article

(This article belongs to the Special Issue Immunomarkers and Molecular Markers in the Diagnosis of Malignant Tumors)

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11 pages, 513 KiB

Open AccessArticle

A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure

by Anaïs Corma-Gómez, Juan Macías, Antonio Rivero, Antonio Rivero-Juarez, Ignacio de los Santos, Sergio Reus-Bañuls, Luis Morano, Dolores Merino, Rosario Palacios, Carlos Galera, Marta Fernández-Fuertes, Alejandro González-Serna, Itziar de Rojas, Agustín Ruiz, María E. Sáez, Luis M. Real and Juan A. Pineda

Diagnostics 2021, 11(8), 1501; https://doi.org/10.3390/diagnostics11081501 - 20 Aug 2021

Cited by 2 | Viewed by 2976

Abstract

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV [...] Read more.

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes. Full article

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

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10 pages, 1034 KiB

Open AccessArticle

Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer

by Antonella Cormio, Gian Maria Busetto, Clara Musicco, Francesca Sanguedolce, Beppe Calò, Marco Chirico, Ugo Giovanni Falagario, Giuseppe Carrieri, Claudia Piccoli and Luigi Cormio

Diagnostics 2021, 11(8), 1500; https://doi.org/10.3390/diagnostics11081500 - 20 Aug 2021

Cited by 3 | Viewed by 2101

Abstract

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The [...] Read more.

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The study population consisted of patients scheduled for transurethral resection of bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladder tumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 and ClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2 and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-risk NMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expression levels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins. Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpP levels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTC scores showed that Mfn2 downregulation was significantly associated with disease progression. In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared to non-lesional bladder tissue and Mfn2 expression predicted disease progression. Full article

(This article belongs to the Special Issue Biomarkers and Therapeutic Advances in Bladder Cancer)

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14 pages, 2403 KiB

Open AccessArticle

Urinary mRNA Expression of Glomerular Podocyte Markers in Glomerular Disease and Renal Transplant

by Silvia Armelloni, Deborah Mattinzoli, Masami Ikehata, Carlo Alfieri, Mirco Belingheri, Gabrilella Moroni, Donata Cresseri, Patrizia Passerini, Roberta Cerutti and Piergiorgio Messa

Diagnostics 2021, 11(8), 1499; https://doi.org/10.3390/diagnostics11081499 - 20 Aug 2021

Cited by 2 | Viewed by 2709

Abstract

The research of novel markers in urinary samples, for the description of renal damage, is of high interest, and several works demonstrated the value of urinary mRNA quantification for the search of events related to renal disease or affecting the outcome of transplant [...] Read more.

The research of novel markers in urinary samples, for the description of renal damage, is of high interest, and several works demonstrated the value of urinary mRNA quantification for the search of events related to renal disease or affecting the outcome of transplant kidneys. In the present pilot study, a comparison of the urine mRNA expression of specific podocyte markers among patients who had undergone clinical indication to renal transplanted (RTx, n = 20) and native (N, n = 18) renal biopsy was performed. The aim of this work was to identify genes involved in podocytes signaling and cytoskeletal regulation (NPHS1, NPHS2, SYNPO, WT1, TRPC6, GRM1, and NEUROD) in respect to glomerular pathology. We considered some genes relevant for podocytes signaling and for the function of the glomerular filter applying an alternative normalization approach. Our results demonstrate the WT1 urinary mRNA increases in both groups and it is helpful for podocyte normalization. Furthermore, an increase in the expression of TRPC6 after all kinds of normalizations was observed. According to our data, WT1 normalization might be considered an alternative approach to correct the expression of urinary mRNA. In addition, our study underlines the importance of slit diaphragm proteins involved in calcium disequilibrium, such as TRPC6. Full article

(This article belongs to the Collection Biomarkers in Medicine)

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Staining of functional molecules in urinary podocytes. GRM1, TRPC6, and NEUROD (A–C) double staining with, respectively, synaptopodin, nephrin, and WT1 (D–F); Merge between A–C and D–F (G–I) cytoplasmic and nuclear podocyte markers were detected in urinary podocytes. DAPI Nuclear staining (blue) shows the absence of apoptosis. Scale bar is 100 µm. Full article ">Figure 2
Cytoskeleton remodelling. Actin detected by phalloidin staining (red) shows different distribution in urinary cells of both N and RTx. WT1 nuclear staining identifies the podocytes (green); Podocyte with actin bundles aligned in the cytoplasm (A,B); other podocytes with altered appearances with round shapes, thickened actin bundles at the cell boundaries, and limited cytoplasmic stress fibers (C,D) DAPI (blue) nuclear staining shows the absence of apoptosis. Scale bar is 100 µm. Full article ">Figure 3
Actin distribution. Stress fibers (red) are visible in podocytes as dorsal, ventral, and transverse arcs (A), or disrupted and distributed along the edge of the cell and poorly expressed in the cytoplasm. (B) Double staining with nuclear podocyte marker WT1 (green) to demonstrate podocyte staining and DAPI (blue) nuclear marker. Scale bar is 100 µm. Full article ">Figure 4
mRNA quantification of urinary cells. mRNA expression was measured in CTR, N, and RTx by RTqPCR, relative to GAPDH and corrected with UC. In the first image top left, the values are expressed as 2−ΔΔct/UC as mean ± standard error to display the amount of gene expression in each group of the sample. Differently, in the subsequent histograms, the results are expressed relative to the control group as mean fold expression ± standard error, to compare the groups. Significance * p < 0.05. Full article ">Figure 5
RTqPCR normalization for podocyte number. The fold expression of genes normalized with GAPDH was further normalized using the expression of, respectively, NPHS1, SYNPO, and WT1, followed by UC correction. Significance * p < 0.05. p-values (lower figure) obtained by comparison with the CTRL are calculated with two-tailed unpaired t-test. Full article ">

14 pages, 4918 KiB

Open AccessArticle

Computer-Aided Detection (CADe) System with Optical Coherent Tomography for Melanin Morphology Quantification in Melasma Patients

by I-Ling Chen, Yen-Jen Wang, Chang-Cheng Chang, Yu-Hung Wu, Chih-Wei Lu, Jia-Wei Shen, Ling Huang, Bor-Shyh Lin and Hsiu-Mei Chiang

Diagnostics 2021, 11(8), 1498; https://doi.org/10.3390/diagnostics11081498 - 19 Aug 2021

Cited by 15 | Viewed by 3729

Abstract

Dark skin-type individuals have a greater tendency to have pigmentary disorders, among which melasma is especially refractory to treat and often recurs. Objective measurement of melanin amount helps evaluate the treatment response of pigmentary disorders. However, naked-eye evaluation is subjective to weariness and [...] Read more.

Dark skin-type individuals have a greater tendency to have pigmentary disorders, among which melasma is especially refractory to treat and often recurs. Objective measurement of melanin amount helps evaluate the treatment response of pigmentary disorders. However, naked-eye evaluation is subjective to weariness and bias. We used a cellular resolution full-field optical coherence tomography (FF-OCT) to assess melanin features of melasma lesions and perilesional skin on the cheeks of eight Asian patients. A computer-aided detection (CADe) system is proposed to mark and quantify melanin. This system combines spatial compounding-based denoising convolutional neural networks (SC-DnCNN), and through image processing techniques, various types of melanin features, including area, distribution, intensity, and shape, can be extracted. Through evaluations of the image differences between the lesion and perilesional skin, a distribution-based feature of confetti melanin without layering, two distribution-based features of confetti melanin in stratum spinosum, and a distribution-based feature of grain melanin at the dermal–epidermal junction, statistically significant findings were achieved (p-values = 0.0402, 0.0032, 0.0312, and 0.0426, respectively). FF-OCT enables the real-time observation of melanin features, and the CADe system with SC-DnCNN was a precise and objective tool with which to interpret the area, distribution, intensity, and shape of melanin on FF-OCT images. Full article

(This article belongs to the Special Issue Advances in Skin Lesion Image Analysis Using Machine Learning Approaches)

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Block diagram of the proposed computer-aided detection (CADe) system. Full article ">Figure 2
The deep learning architecture of the denoising convolutional neural network (DnCNN). Full article ">Figure 3
Schematic diagram of how to generate low-speckle ground truth images. Full article ">Figure 4
The structure of the spatial compounding-based denoising convolutional neural networks (SC-DnCNN) trained for optical coherence tomography (OCT) denoising. Full article ">Figure 5
Illustration of automatic melanin segmentation in CADe system. (a) Clinical image of the imaged melasma lesions (rectangular) on the cheek. (b) The original en face scan (E-scan) image. (c) The image after SC-DnCNN. (d) The image after performing contrast-limited adaptive histogram equalization (CLAHE). (e) The candidate targets segmented by thresholding. (f) The selected grain melanin after image opening. (g) The selected confetti melanin after morphological operations. The field of view is 475 × 476 µm. Full article ">Figure 6
The performance comparison of CADe with and without SC-DnCNN on the representative lesion images. (a,b) are the input image and the denoised image, respectively, while (c,d) are the output results when superimposing the detected melanin on those images (grain melanin is represented in red, and confetti melanin is represented in yellow), respectively. The field of view is 475 × 476 µm. Full article ">Figure 7
The performance comparison of CADe with and without SC-DnCNN on the perilesional skin images. (a,b) are the input image and the denoised image, respectively, while (c,d) are the output results when superimposing the detected melanin on those images (grain melanin is represented in red, and confetti melanin is represented in yellow), respectively. The field of view is 475 × 476 µm. Full article ">Figure 8
Comparison of melanin appearance between the representative lesion and perilesional skin images in different skin layers displayed by the CADe system. (a–f) are the perilesional skin images and the lesion images in the stratum spinosum, dermal–epidermal junction (DEJ), and papillary dermis, respectively. The field of view is 475 × 476 µm. Full article ">

18 pages, 1334 KiB

Open AccessArticle

Residual-Shuffle Network with Spatial Pyramid Pooling Module for COVID-19 Screening

by Mohd Asyraf Zulkifley, Siti Raihanah Abdani, Nuraisyah Hani Zulkifley and Mohamad Ibrani Shahrimin

Diagnostics 2021, 11(8), 1497; https://doi.org/10.3390/diagnostics11081497 - 19 Aug 2021

Cited by 4 | Viewed by 2763

Abstract

Since the start of the COVID-19 pandemic at the end of 2019, more than 170 million patients have been infected with the virus that has resulted in more than 3.8 million deaths all over the world. This disease is easily spreadable from one [...] Read more.

Since the start of the COVID-19 pandemic at the end of 2019, more than 170 million patients have been infected with the virus that has resulted in more than 3.8 million deaths all over the world. This disease is easily spreadable from one person to another even with minimal contact, even more for the latest mutations that are more deadly than its predecessor. Hence, COVID-19 needs to be diagnosed as early as possible to minimize the risk of spreading among the community. However, the laboratory results on the approved diagnosis method by the World Health Organization, the reverse transcription-polymerase chain reaction test, takes around a day to be processed, where a longer period is observed in the developing countries. Therefore, a fast screening method that is based on existing facilities should be developed to complement this diagnosis test, so that a suspected patient can be isolated in a quarantine center. In line with this motivation, deep learning techniques were explored to provide an automated COVID-19 screening system based on X-ray imaging. This imaging modality is chosen because of its low-cost procedures that are widely available even in many small clinics. A new convolutional neural network (CNN) model is proposed instead of utilizing pre-trained networks of the existing models. The proposed network, Residual-Shuffle-Net, comprises four stacks of the residual-shuffle unit followed by a spatial pyramid pooling (SPP) unit. The architecture of the residual-shuffle unit follows an hourglass design with reduced convolution filter size in the middle layer, where a shuffle operation is performed right after the split branches have been concatenated back. Shuffle operation forces the network to learn multiple sets of features relationship across various channels instead of a set of global features. The SPP unit, which is placed at the end of the network, allows the model to learn multi-scale features that are crucial to distinguish between the COVID-19 and other types of pneumonia cases. The proposed network is benchmarked with 12 other state-of-the-art CNN models that have been designed and tuned specially for COVID-19 detection. The experimental results show that the Residual-Shuffle-Net produced the best performance in terms of accuracy and specificity metrics with 0.97390 and 0.98695, respectively. The model is also considered as a lightweight model with slightly more than 2 million parameters, which makes it suitable for mobile-based applications. For future work, an attention mechanism can be integrated to target certain regions of interest in the X-ray images that are deemed to be more informative for COVID-19 diagnosis. Full article

(This article belongs to the Special Issue Machine Learning Applications for COVID-19 and Its Complications: Screening, Diagnosis, Treatment, and Prognosis)

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11 pages, 1036 KiB

Open AccessArticle

Quantitative SARS-CoV-2 Spike Antibody Response in COVID-19 Patients Using Three Fully Automated Immunoassays and a Surrogate Virus Neutralization Test

by Yoonjoo Kim, Ji Hyun Lee, Geon Young Ko, Ji Hyeong Ryu, Joo Hee Jang, Hyunjoo Bae, Seung-Hyo Yoo, Ae-Ran Choi, Jin Jung, Jongmin Lee and Eun-Jee Oh

Diagnostics 2021, 11(8), 1496; https://doi.org/10.3390/diagnostics11081496 - 19 Aug 2021

Cited by 32 | Viewed by 5960

Abstract

Quantitative SARS-CoV-2 antibody assays against the spike (S) protein are useful for monitoring immune response after infection or vaccination. We compared the results of three chemiluminescent immunoassays (CLIAs) (Abbott, Roche, Siemens) and a surrogate virus neutralization test (sVNT, GenScript) using 191 sequential samples [...] Read more.

Quantitative SARS-CoV-2 antibody assays against the spike (S) protein are useful for monitoring immune response after infection or vaccination. We compared the results of three chemiluminescent immunoassays (CLIAs) (Abbott, Roche, Siemens) and a surrogate virus neutralization test (sVNT, GenScript) using 191 sequential samples from 32 COVID-19 patients. All assays detected >90% of samples collected 14 days after symptom onset (Abbott 97.4%, Roche 96.2%, Siemens 92.3%, and GenScript 96.2%), and overall agreement among the four assays was 91.1% to 96.3%. When we assessed time-course antibody levels, the Abbott and Siemens assays showed higher levels in patients with severe disease (p < 0.05). Antibody levels from the three CLIAs were correlated (r = 0.763–0.885). However, Passing–Bablok regression analysis showed significant proportional differences between assays and converting results to binding antibody units (BAU)/mL still showed substantial bias. CLIAs had good performance in predicting sVNT positivity (Area Under the Curve (AUC), 0.959–0.987), with Abbott having the highest AUC value (p < 0.05). SARS-CoV-2 S protein antibody levels as assessed by the CLIAs were not interchangeable, but showed reliable performance for predicting sVNT results. Further standardization and harmonization of immunoassays might be helpful in monitoring immune status after COVID-19 infection or vaccination. Full article

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

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Positivity rate of three SARS-CoV-2 S protein antibody chemiluminescent assays and the surrogate virus neutralization test according to days after symptom onset. Full article ">Figure 2
SARS-CoV-2 S protein antibody levels by three chemiluminescent immunoassays and the surrogate virus neutralization test in COVID-19 patients according to days after symptom onset and disease severity. (a) Abbott, (b) Roche, (c) Siemens and (d) Genscript. Patients with severe (critical or severe) and mild disease courses are indicated in red and blue, respectively. (* p < 0.05). Full article ">Figure 3
Comparison between binding antibody levels (converted to binding antibody unit (BAU)/mL) from three SARS-CoV-2 S protein antibody immunoassays by Passing–Bablok regression analysis. (a) Abbott vs. Roche, (b) Abbott vs. Siemens and (c) Siemens vs. Roche. Full article ">Figure 4
Comparison of quantitative SARS-CoV-2 S protein antibody levels and neutralizing antibody values by surrogate virus neutralization test. (a–c) Correlations between quantitative concentrations by three CLIAs and percent inhibition by sVNT. (d) Comparison of ROC curve analysis to predict sVNT positivity (>30%) for three CLIAs (Abbott, Roche, and Siemens assays). * AUC value. Full article ">

8 pages, 897 KiB

Open AccessSystematic Review

Perivascular Adipose Tissue Attenuation on Computed Tomography beyond the Coronary Arteries. A Systematic Review

by Domenico Tuttolomondo, Chiara Martini, Francesco Nicolini, Francesco Formica, Alessandro Pini, Francesco Secchi, Riccardo Volpi, Massimo De Filippo and Nicola Gaibazzi

Diagnostics 2021, 11(8), 1495; https://doi.org/10.3390/diagnostics11081495 - 19 Aug 2021

Cited by 7 | Viewed by 2785

Abstract

(1) Background: Perivascular adipose tissue attenuation, measured with computed tomography imaging, is a marker of mean local vascular inflammation since it reflects the morphological changes of the fat tissue in direct contact with the vessel. This method is thoroughly validated in coronary arteries, [...] Read more.

(1) Background: Perivascular adipose tissue attenuation, measured with computed tomography imaging, is a marker of mean local vascular inflammation since it reflects the morphological changes of the fat tissue in direct contact with the vessel. This method is thoroughly validated in coronary arteries, but few studies have been performed in other vascular beds. The aim of the present study is to provide insight into the potential application of perivascular adipose tissue attenuation through computed tomography imaging in extra-coronary arteries. (2) Methods: A comprehensive search of the scientific literature published in the last 30 years (1990–2020) has been performed on Medline. (3) Results: A Medline databases search for titles, abstracts, and keywords returned 3251 records. After the exclusion of repetitions and the application of inclusion and exclusion criteria and abstract screening, 37 studies were selected for full-text evaluation. Three papers were finally included in the systematic review. Perivascular adipose tissue attenuation assessment was studied in the internal carotid artery, ascending thoracic aorta, and abdominal aorta. (4) Conclusions: Perivascular adipose tissue attenuation seems to be an applicable parameter in all investigated vascular beds, generally with good inter-observer reproducibility. Full article

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

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12 pages, 3233 KiB

Open AccessArticle

Metabolic Changes in Maternal and Cord Blood in One Case of Pregnancy-Associated Breast Cancer Seen by Fluorescence Lifetime Imaging Microscopy

by Li Zhou, Yawei Kong, Junxin Wu, Xingzhi Li, Yiyan Fei, Jiong Ma, Yulan Wang and Lan Mi

Diagnostics 2021, 11(8), 1494; https://doi.org/10.3390/diagnostics11081494 - 19 Aug 2021

Viewed by 2450

Abstract

Pregnancy-associated breast cancer (PABC) is a rare disease, which is frequently diagnosed at an advanced stage due to limitations in current diagnostic methods. In this study, fluorescence lifetime imaging microscopy (FLIM) was used to study the metabolic changes by measuring maternal blood and [...] Read more.

Pregnancy-associated breast cancer (PABC) is a rare disease, which is frequently diagnosed at an advanced stage due to limitations in current diagnostic methods. In this study, fluorescence lifetime imaging microscopy (FLIM) was used to study the metabolic changes by measuring maternal blood and umbilical cord blood via the autofluorescence of coenzymes, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), and flavin adenine dinucleotide (FAD). The NAD(P)H data showed that a PABC case had significant differences compared with normal cases, which may indicate increased glycolysis. The FAD data showed that both maternal and cord blood of PABC had shorter mean lifetimes and higher bound-FAD ratios. The significant differences suggested that FLIM testing of blood samples may be a potential method to assist in PABC non-radiative screening. Full article

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

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Diagram of sample preparation and equipment. (A) Preparation of blood glass smear. (B) Schematic diagram of placental sampling at various sites as marked by the yellow boxes. (C) FLIM setup. Full article ">Figure 2
Representative NAD(P)H FLIM images and their distribution curves of normal and PABC cases. (A,B,D,E) tm and a2 images of maternal blood, (G,H,J,K) tm and a2 images of umbilical cord blood. (C,F,I,L) Distribution curves of corresponding images. Scale bar: 10 μm. Full article ">Figure 3
The average NAD(P)H tm and a2 distribution curve peak heights of PABC and the normal group (including seven pairs of normal maternal blood and umbilical cord blood, N1-N7). (A) NAD(P)H-tm peak 2 height in maternal blood, (B) NAD(P)H-a2 peak 3 height in maternal blood, (C) NAD(P)H-tm peak 2 height in cord blood, and (D) NAD(P)H-a2 peak 3 height in cord blood (** p <0.01, *** p <0.001, **** p <0.0001). Full article ">Figure 4
Representative FAD FLIM images and their distribution curves of PABC and normal cases. (A,B,D,E) tm and a1 images of maternal blood, (G,H,J,K) tm and a1 images of umbilical cord blood. (C,F,I,L) Distribution curves of corresponding images. Scale bar: 10 μm. Full article ">Figure 5
The FWHM of the FAD tm and a1 distribution curves of PABC and the normal group (including seven pairs of normal maternal blood and umbilical cord blood, N1-N7). (A) FAD-tm of maternal blood, (B) FAD-a1 of maternal blood, (C) FAD-tm of cord blood, (D) FAD-a1 of cord blood (** p < 0.01, *** p < 0.001, **** p < 0.0001). Full article ">

11 pages, 5664 KiB

Open AccessCase Report

Traumatic Intralenticular Neovascularization in a HLA B27+ Pediatric Patient

by Călin Petru Tătaru, Cătălina Ioana Tătaru, Maria Dudău, Alexandra Moșu, Lăcrămioara Luca, Bosa Maria, Alice Bancu and Paul Filip Curcă

Diagnostics 2021, 11(8), 1493; https://doi.org/10.3390/diagnostics11081493 - 18 Aug 2021

Viewed by 2082

Abstract

(1) Background: Intralenticular tumors are an entity akin to Schrodinger’s cat since, although the human crystalline cells themselves are not known to malignly proliferate, various entities can take the appearance and clinical presentation of a tumor originating in the lens. We present the [...] Read more.

(1) Background: Intralenticular tumors are an entity akin to Schrodinger’s cat since, although the human crystalline cells themselves are not known to malignly proliferate, various entities can take the appearance and clinical presentation of a tumor originating in the lens. We present the peculiar case of an 11-year-old male patient of African descent, HLA B27+, with a previous history of minor ocular trauma and unilateral anterior uveitis a year before which was admitted to our department with total opacification of the crystalline lens in the right eye and lens neovascularization. During surgery, a vascular, white fibrotic mass measuring 0.1–0.2 cm was discovered inside the lens bag and was excised. (2) Methods: Retrospective case review. (3) Results: The histopathological exam of the excised mass revealed an abundant infiltrate consisting of CD68+ foamy macrophages and lymphoplasmacytic elements. CD68 is a pan-macrophage marker associated with an active inflammatory mechanism soliciting macrophages, and tissue activated macrophages are correlated to increased stromal and serum levels of vascular endothelial growth factor, providing an explanation for lens angiogenesis. (4) Conclusions: The diagnosis is of a “masquerade tumor” resulted from an abnormal inflammatory process in connection with previous ocular trauma and possibly the patient’s HLA B27+ status. Full article

(This article belongs to the Special Issue New Frontiers in Diagnostics for Cataract Surgery)

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16x magnification slit-lamp biomicroscopy images of the patient’s right eye. (A) Reveals an opaque lens. (B) Enhanced (zoomed-in) close-up image that reveals the presence of fine blood vessels located intralenticularly. Full article ">Figure 2
Intraoperative images—Initial aspect (A). During the surgery, the anterior capsule was firmly attached to the lens by fibrous adherences (B–D), which presented neovascularization, and a small amount of blood was discharged after manipulation (C). After aspiration of the lens material a vascular fibrotic tissue previously covered by the cortex and anterior capsule was discovered in the lens bag (E), with a greater consistency than the lens and a visible blood-vessel. The specimen was excised (F) and sent for histopathological examination. A fibrous vascularized proliferation remains attached in the supero-temporal region of the posterior capsule (G). A posterior capsulorhexis (H) with limited anterior vitrectomy and the excision of the fibrous proliferation were performed. The lens was implanted by using the technique of posterior optic capture, and the surgery was conducted without other complications (I). Full article ">Figure 3
HE stain, 4×. (A) indicates a resection artifact. (B) The inflammatory infiltrate of foamy macrophages and lymphoplasmacytic elements. (C) indicates an abundance of immature collagen fibers. Full article ">Figure 4
HE stain, 10× lens. Foamy macrophages predominantly centrally located. Numerous loose collagen fibers are present throughout the specimen, with more located toward the periphery. Full article ">Figure 5
HE stain 40× lens—close-up view of the inflammatory infiltrate. (A) highlights the foamy macrophages. (B) indicates immature collagen fibers. (C,D) note the presence of lymphoplasmacytes. Full article ">Figure 6
Van Gieson’s stain, 20× lens—close-up of the immature collagen fibers. Full article ">Figure 7
Immunohistochemical analysis using CD68 staining antibodies. (A) using 10× lens: the overall picture is of a highly metabolically active granulation tissue that is not yet matured. (B) using 20× lens: intense positivity and diffuse capture in the cytoplasm of the macrophages, identifying them as CD68+ foamy macrophages. Full article ">

15 pages, 3427 KiB

Open AccessArticle

An Artificial Intelligence-Enabled Pipeline for Medical Domain: Malaysian Breast Cancer Survivorship Cohort as a Case Study

by Mogana Darshini Ganggayah, Sarinder Kaur Dhillon, Tania Islam, Foad Kalhor, Teh Chean Chiang, Elham Yousef Kalafi and Nur Aishah Taib

Diagnostics 2021, 11(8), 1492; https://doi.org/10.3390/diagnostics11081492 - 18 Aug 2021

Cited by 4 | Viewed by 3460

Abstract

Automated artificial intelligence (AI) systems enable the integration of different types of data from various sources for clinical decision-making. The aim of this study is to propose a pipeline to develop a fully automated clinician-friendly AI-enabled database platform for breast cancer survival prediction. [...] Read more.

Automated artificial intelligence (AI) systems enable the integration of different types of data from various sources for clinical decision-making. The aim of this study is to propose a pipeline to develop a fully automated clinician-friendly AI-enabled database platform for breast cancer survival prediction. A case study of breast cancer survival cohort from the University Malaya Medical Centre was used to develop and evaluate the pipeline. A relational database and a fully automated system were developed by integrating the database with analytical modules (machine learning, automated scoring for quality of life, and interactive visualization). The developed pipeline, iSurvive has helped in enhancing data management as well as to visualize important prognostic variables and survival rates. The embedded automated scoring module demonstrated quality of life of patients whereas the interactive visualizations could be used by clinicians to facilitate communication with patients. The pipeline proposed in this study is a one-stop center to manage data, to automate analytics using machine learning, to automate scoring and to produce explainable interactive visuals to enhance clinician-patient communication along the survivorship period to modify behaviours that relate to prognosis. The pipeline proposed can be modelled on any disease not limited to breast cancer. Full article

(This article belongs to the Special Issue Machine Learning in Breast Disease Diagnosis)

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iSurvive development workflow. Full article ">Figure 2
Automated machine learning in iSurvive. Full article ">Figure 3
Digitized questionnaires in iSurvive. Full article ">Figure 4
(a) Bar chart showing model accuracy measures of five algorithms (RF: 92.5%, KNN: 92.4%, LR: 92.3%, DT: 85.0%, NB: 86.0%). (b) The variable importance scores of 16 variables in ascending order (BMI: 0.91, Age: 0.15, Stage: 0.14, Income: 0.07, Menarche: 0.06, Marital status: 0.05, Ethnicity: 0.05, CERB2 status: 0.04, Education: 0.04, PR status: 0.03, Occupation: 0.02, ER status: 0.02, Menopausal: 0.02, Recurrence: 0.02, Alcohol intake: 0.01, Smoking status (0.01), Stress level: 0.00). Full article ">Figure 5
Survival curves using BMI and survival years. Full article ">Figure 6
Quality-of-life scoring page of iSurvive. Full article ">Figure 7
Interactive visualization showing the reports on personal information, comorbidity, physical activity measure, and distress level of a selected patient. Full article ">Figure 8
Quality-of-life chart, which can be exported to pdf from iSurvive. Full article ">

14 pages, 2337 KiB

Open AccessArticle

Radiomics Nomogram Based on Radiomics Score from Multiregional Diffusion-Weighted MRI and Clinical Factors for Evaluating HER-2 2+ Status of Breast Cancer

by Chunli Li and Jiandong Yin

Diagnostics 2021, 11(8), 1491; https://doi.org/10.3390/diagnostics11081491 - 18 Aug 2021

Cited by 16 | Viewed by 3319

Abstract

This study aimed to establish and validate a radiomics nomogram using the radiomics score (rad-score) based on multiregional diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) features combined with clinical factors for evaluating HER-2 2+ status of breast cancer. A total of 223 [...] Read more.

This study aimed to establish and validate a radiomics nomogram using the radiomics score (rad-score) based on multiregional diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) features combined with clinical factors for evaluating HER-2 2+ status of breast cancer. A total of 223 patients were retrospectively included. Radiomic features were extracted from multiregional DWI and ADC images. Based on the intratumoral, peritumoral, and combined regions, three rad-scores were calculated using the logistic regression model. Independent parameters were selected among clinical factors and combined rad-score (com-rad-score) using multivariate logistic analysis and used to construct a radiomics nomogram. The performance of the nomogram was evaluated using calibration, discrimination, and clinical usefulness. The areas under the receiver operator characteristic curve (AUCs) of intratumoral and peritumoral rad-scores were 0.824/0.763 and 0.794/0.731 in the training and validation cohorts, respectively. Com-rad-score achieved the highest AUC (0.860/0.790) among three rad-scores. ER status and com-rad-score were selected to establish the nomogram, which yielded good discrimination (AUC: 0.883/0.848) and calibration. Decision curve analysis demonstrated the clinical value of the nomogram in the validation cohort. In conclusion, radiomics nomogram, including clinical factors and com-rad-score, showed favorable performance for evaluating HER-2 2+ status in breast cancer. Full article

(This article belongs to the Special Issue Advancement in Breast Diagnostic and Interventional Radiology)

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Figure 1
Flowchart of this study. (a) Image data (DWIb=0, DWIb=800, and ADC) was collected. (b) Intra- and peritumoral regions (red masks) were obtained using semi-automatic segmentation. (c) A total of 2504 radiomic features were extracted from three images, and ICC analysis and three-step feature selection were performed. (d) Three rad-scores were calculated with the selected features using the logistic regression model and evaluated. (e) Independent parameters were selected among clinical factors and combined rad-score (com-rad-score) using multivariate logistic analysis and used to establish a radiomics nomogram. ICC, intraclass correlation coefficient; WLCX, Wilcoxon rank-sum test; MRMR, minimum redundancy maximum relevance; ROC, receiver operating characteristic. Full article ">Figure 2
Intratumoral segmentation, peritumoral segmentation, pathology, and FISH results of randomly selected cases with negative and positive HER-2 2+. Case with negative HER-2 2+: (a) DWIb=0, (b) DWIb=800, (c) ADC map, (d) pathology findings, and (e) FISH results. Case with positive HER-2 2+: (f) DWIb=0, (g) DWIb=800, (h) ADC map, (i) pathology findings, and (j) FISH results. The white and red lines indicate the intratumoral and peritumoral margins on DWIb=0, DWIb=800, and ADC images, respectively. Full article ">Figure 3
Dot diagram of the three rad-scores in the training (positive: n = 75, negative: n = 92) and validation (positive: n = 22, negative: n = 34) cohorts. Dot diagram of the intra-rad-score in the training (a) and validation (b) cohorts. Dot diagram of the peri-rad-score in the training (c) and validation (d) cohorts. Dot diagram of the com-rad-score in the training (e) and validation (f) cohorts. Full article ">Figure 4
ROC curves of the three rad-scores in each cohort. (a) ROC curves of the three rad-scores in the training cohort. (b) ROC curves of the three rad-scores in the validation cohort. Full article ">Figure 5
Radiomics nomogram incorporating the com-rad-score and ER status. Full article ">Figure 6
ROC curves for the radiomics nomogram in each cohort. (a) ROC curve for the radiomics nomogram in the training cohort. (b) ROC curve for the radiomics nomogram in the validation cohort. Full article ">Figure 7
Calibration curves of the radiomics nomogram in each cohort. (a) Calibration curve of the radiomics nomogram in the training cohort. (b) Calibration curve of the radiomics nomogram in the validation cohort. Full article ">Figure 8
DCA for the radiomics nomogram in the validation cohort. Full article ">

3 pages, 716 KiB

Open AccessInteresting Images

An Incidental Pancreatic Finding at 18F-Choline PET/CT: Chronic Mass-Forming Pancreatitis

by Laura Evangelista, Alessandro De Pellegrin, Rossano Girometti, Gianluca Cassarino, Francesco Giacomuzzi and Marco Rensi

Diagnostics 2021, 11(8), 1490; https://doi.org/10.3390/diagnostics11081490 - 17 Aug 2021

Viewed by 2518

Abstract

We present a case of a chronic mass-forming pancreatitis (CMFP) detected by 18F-choline (FCH) PET/CT in a male affected by prostate cancer. FCH PET/CT scan showed a focal uptake in the uncinate process of the pancreas, later diagnosed as a CMFP at biopsy. [...] Read more.

We present a case of a chronic mass-forming pancreatitis (CMFP) detected by 18F-choline (FCH) PET/CT in a male affected by prostate cancer. FCH PET/CT scan showed a focal uptake in the uncinate process of the pancreas, later diagnosed as a CMFP at biopsy. Although the physiological distribution of FCH in the pancreas, a careful interpretation of the images in this area is warranted. Full article

(This article belongs to the Collection Interesting Images)

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Diagnostics, Volume 11, Issue 8 (August 2021) – 217 articles

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