Diagnostics

15 pages, 3702 KiB

Open AccessArticle

A Prospective Study Comparing Three-Dimensional Rectal Water Contrast Transvaginal Ultrasonography and Computed Tomographic Colonography in the Diagnosis of Rectosigmoid Endometriosis

by Fabio Barra, Ennio Biscaldi, Carolina Scala, Antonio Simone Laganà, Valerio Gaetano Vellone, Cesare Stabilini, Fabio Ghezzi and Simone Ferrero

Diagnostics 2020, 10(4), 252; https://doi.org/10.3390/diagnostics10040252 - 24 Apr 2020

Cited by 22 | Viewed by 4880

Abstract

(1) Objectives: In patients with symptoms suggestive of rectosigmoid endometriosis, imaging techniques are required to confirm the presence and establish the extent of the disease. The objective of the current study was to compare the performance of three-dimensional rectal water contrast transvaginal ultrasonography [...] Read more.

(1) Objectives: In patients with symptoms suggestive of rectosigmoid endometriosis, imaging techniques are required to confirm the presence and establish the extent of the disease. The objective of the current study was to compare the performance of three-dimensional rectal water contrast transvaginal ultrasonography (3D-RWC-TVS) and computed tomographic colonography (CTC) in predicting the presence and characteristics of rectosigmoid endometriosis. (2) Methods: This prospective study included patients with suspicion of rectosigmoid endometriosis who underwent both 3D-RWC-TVS and CTC and subsequently were surgically treated. The findings of imaging techniques were compared with surgical and histological results. (3) Results: Out of 68 women included in the study, 37 (48.9; 95% C.I. 38.2–59.7%) had rectosigmoid nodules and underwent bowel surgery. There was no significant difference in the accuracy of 3D-RWC-TVS and CTC in diagnosing the presence of rectosigmoid endometriotic nodules (p = 0.118), although CTC was more precise in diagnosing endometriosis located in the sigmoid (p = 0.016). 3D-RWC-TVS and CTC had similar precision in estimating the largest diameter of the main endometriotic nodule (p = 0.099) and, in patients undergoing segmental resection, the degree of the stenosis of the bowel lumen (p = 0.293). CTC was more accurate in estimating the distance between the lower margin of the intestinal nodule and the anal verge (p = 0.030) but was less tolerated than 3D-RWC-TVS (p < 0.001). (4) Conclusion: This was the first study comparing the performance of 3D-RWC-TVS and CTC in the diagnosis of rectosigmoid endometriosis. Both techniques allowed for the evaluation of the profile of the bowel lumen in a pseudoendoscopic fashion and had a similar performance for the diagnosis of rectosigmoid endometriosis, although CTC was more accurate in diagnosing and characterizing sigmoid nodules. Full article

(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)

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9 pages, 686 KiB

Open AccessArticle

Unstimulated Parotid Saliva Sampling in Juvenile Idiopathic Arthritis and Healthy Controls: A Proof-of-Concept Study on Biomarkers

by Alexandra Dimitrijevic Carlsson, Bijar Ghafouri, Carin Starkhammar Johansson and Per Alstergren

Diagnostics 2020, 10(4), 251; https://doi.org/10.3390/diagnostics10040251 - 24 Apr 2020

Cited by 4 | Viewed by 4133

Abstract

The aims of this proof-of-concept study were to develop a collecting method for unstimulated parotid saliva in juvenile idiopathic arthritis (JIA) patients and healthy children and to investigate if inflammatory biomarkers could be detected in these samples. Forty-five children with JIA (median age [...] Read more.

The aims of this proof-of-concept study were to develop a collecting method for unstimulated parotid saliva in juvenile idiopathic arthritis (JIA) patients and healthy children and to investigate if inflammatory biomarkers could be detected in these samples. Forty-five children with JIA (median age of 12 years and 25th–75th percentile of 10–15 years; 33 girls and 12 boys) and 16 healthy children as controls (median age of 13 years and 25–75th percentile of 10–13 years; 11 girls and 5 boys) were enrolled in this study. Unstimulated parotid saliva was collected with a modified Carlson–Crittenden collector. The salivary flow rate and salivary concentrations of total protein and inflammatory mediators were assessed. The Meso Scale Discovery electrochemiluminescence immunoassay was used for analyzing protein concentrations and the inflammatory biomarkers. Sufficient parotid saliva volumes to be analyzed could be collected with the collection device. JIA patients had a lower sampling saliva volume (p = 0.008) and saliva flow rate (p = 0.039) than controls. The total protein concentrations and inflammatory biomarkers were measured in the last six healthy subjects. The median protein concentration was 1312 µg/mL (25th percentile: 844 µg/mL and 75th percentile: 2062 µg/mL; n = 6) and quantifiable concentrations of 39 inflammatory proteins could be assessed in these samples. In conclusion, this study indicates that the saliva sampling method, as used in the present study, is able to collect sufficient sample volumes in children, and that it is possible to analyze various inflammatory biomarkers in the collected saliva. Full article

(This article belongs to the Special Issue Salivary Biomarkers and Their Application to Diagnosis and Monitoring Human Diseases)

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17 pages, 1453 KiB

Open AccessArticle

Molecular Diagnostic of Solid Tumor Using a Next Generation Sequencing Custom-Designed Multi-Gene Panel

by Dario de Biase, Giorgia Acquaviva, Michela Visani, Viviana Sanza, Chiara M. Argento, Antonio De Leo, Thais Maloberti, Annalisa Pession and Giovanni Tallini

Diagnostics 2020, 10(4), 250; https://doi.org/10.3390/diagnostics10040250 - 23 Apr 2020

Cited by 48 | Viewed by 4720

Abstract

Next generation sequencing (NGS) allows parallel sequencing of multiple genes at a very high depth of coverage. The need to analyze a variety of targets for diagnostic/prognostic/predictive purposes requires multi-gene characterization. Multi-gene panels are becoming standard approaches for the molecular analysis of solid [...] Read more.

Next generation sequencing (NGS) allows parallel sequencing of multiple genes at a very high depth of coverage. The need to analyze a variety of targets for diagnostic/prognostic/predictive purposes requires multi-gene characterization. Multi-gene panels are becoming standard approaches for the molecular analysis of solid lesions. We report a custom-designed 128 multi-gene panel engineered to cover the relevant targets in 22 oncogene/oncosuppressor genes for the analysis of the solid tumors most frequently subjected to routine genotyping. A total of 1695 solid tumors were analyzed for panel validation. The analytical sensitivity is 5%. Analytical validation: (i) Accuracy: sequencing results obtained using the multi-gene panel are concordant using two different NGS platforms and single-gene approach sequencing (100% of 83 cases); (ii) Precision: consistent results are obtained in the samples analyzed twice with the same platform (100% of 20 cases). Clinical validation: the frequency of mutations identified in different tumor types is consistent with the published literature. This custom-designed multi-gene panel allows to analyze with high sensitivity and throughput 22 oncogenes/oncosuppressor genes involved in diagnostic/prognostic/predictive characterization of central nervous system tumors, non-small-cell lung carcinomas, colorectal carcinomas, thyroid nodules, pancreatic lesions, melanoma, oral squamous carcinomas and gastrointestinal stromal tumors. Full article

(This article belongs to the Special Issue Next-Generation Sequencing in Tumor Diagnosis and Treatment)

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12 pages, 1916 KiB

Open AccessArticle

Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study

by Hyera Kim, Minji Lim, Jin Young Kim, So-Jin Shin, Yoon-Kyoung Cho and Chi Heum Cho

Diagnostics 2020, 10(4), 249; https://doi.org/10.3390/diagnostics10040249 - 23 Apr 2020

Cited by 15 | Viewed by 5033

Abstract

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in [...] Read more.

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45−, and 4′,6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were <3. CTC counts were correlated with CA125 levels in three patients without recurrence; they were elevated in three patients with recurrence and normal CA125 concentrations. CTC counts and CA125 levels showed high concordance with directional changes (increasing 71.4%; non-increasing 75.0%). CTC counts showed higher associations with clinical status, sensitivity (100.0% vs. 60.0%), positive predictive value (55.6% vs. 42.9%), and negative predictive value (100.0% vs. 87.5%) than CA125 levels. CTC counts were better associated with treatment response and recurrence than CA125 levels. Full article

(This article belongs to the Collection Biomarkers in Medicine)

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16 pages, 337 KiB

Open AccessReview

Dried Blood Spot in Laboratory: Directions and Prospects

by Kristina Malsagova, Artur Kopylov, Alexander Stepanov, Tatyana Butkova, Alexander Izotov and Anna Kaysheva

Diagnostics 2020, 10(4), 248; https://doi.org/10.3390/diagnostics10040248 - 23 Apr 2020

Cited by 70 | Viewed by 10756

Abstract

Over the past few years, dried blood spot (DBS) technology has become a convenient tool in both qualitative and quantitative biological analysis. DBS technology consists of a membrane carrier (MC) on the surface of which a biomaterial sample becomes absorbed. Modern analytical, immunological [...] Read more.

Over the past few years, dried blood spot (DBS) technology has become a convenient tool in both qualitative and quantitative biological analysis. DBS technology consists of a membrane carrier (MC) on the surface of which a biomaterial sample becomes absorbed. Modern analytical, immunological or genomic methods can be employed for analysis after drying the sample. DBS has been described as the most appropriate method for biomaterial sampling due to specific associated inherent advantages, including the small volumes of biomaterials required, the absence of a need for special conditions for samples’ storage and transportation, improved stability of analytes and reduced risk of infection resulting from contaminated samples. This review illustrates information on the current state of DBS technology, which can be useful and helpful for biomedical researchers. The prospects of using this technology to assess the metabolomic profile, assessment, diagnosis of communicable diseases are demonstrated. Full article

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

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12 pages, 2374 KiB

Open AccessArticle

Magnetic Resonance Imaging Derived Biomarkers of IDH Mutation Status and Overall Survival in Grade III Astrocytomas

by Paola Feraco, Antonella Bacci, Patrizia Ferrazza, Luc van den Hauwe, Riccardo Pertile, Salvatore Girlando, Mattia Barbareschi, Cesare Gagliardo, Alessio Giuseppe Morganti and Benedetto Petralia

Diagnostics 2020, 10(4), 247; https://doi.org/10.3390/diagnostics10040247 - 23 Apr 2020

Cited by 13 | Viewed by 3990

Abstract

The evaluation of the isocitrate dehydrogenase (IDH) mutation status in the glioma decision-making process has diagnostic, prognostic and therapeutic implications. The aim of this study was to evaluate whether conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) can noninvasively predict the [...] Read more.

The evaluation of the isocitrate dehydrogenase (IDH) mutation status in the glioma decision-making process has diagnostic, prognostic and therapeutic implications. The aim of this study was to evaluate whether conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) can noninvasively predict the most common IDH mutational status (R132H) in GIII-astrocytomas and the overall survival (OS). Hence, twenty-two patients (9-F, 13-M) with a histological diagnosis of GIII-astrocytoma and evaluation of IDH-mutation status (12-wild type, 10-mutant) were retrospectively evaluated. Imaging studies were reviewed for the morphological feature and mean ADC values (ADCm). Statistics included a Fisher’s exact test, Student’s t-test, Spearman’s Test and receiver operating characteristic analysis. A p ≤ 0.05 value was considered statistically significant for all the tests. A younger age and a frontal location were more likely related to mutational status. IDH-wild type (Wt) exhibited a slight enhancement (p = 0.039). The ADCm values in IDH-mutant (Mut) patients were higher than those of IDH-Wt patients (p < 0.0004). The value of ADC ≥ 0.99 × 10⁻³ mm²/s emerged as a “cut-off” to differentiate the mutation state. In the overall group, a positive relationship between the ADCm values and OS was detected (p = 0.003; r = 0.62). Adding quantitative measures of ADC values to conventional MR imaging could be used routinely as a noninvasive marker of specific molecular patterns. Full article

(This article belongs to the Special Issue Molecular Diagnostics of CNS Tumours)

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10 pages, 1584 KiB

Open AccessArticle

Increased Tissue Expression of Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Is Associated with Disease Severity in Chronic Rhinosinusitis with Nasal Polyps

by Manabu Nishida, Sachio Takeno, Kohta Takemoto, Daisuke Takahara, Takao Hamamoto, Takashi Ishino and Tomohiro Kawasumi

Diagnostics 2020, 10(4), 246; https://doi.org/10.3390/diagnostics10040246 - 23 Apr 2020

Cited by 5 | Viewed by 2650

Abstract

Background: The oxidative stress, induced by both environmental and intrinsic stimuli, underlies the onset and persistency of chronic rhinosinusitis (CRS). Scavenger receptors (SRs) are a broad family of transmembrane receptors involved in a dysfunctional host–environment interaction through a reaction with reactive oxygen species [...] Read more.

Background: The oxidative stress, induced by both environmental and intrinsic stimuli, underlies the onset and persistency of chronic rhinosinusitis (CRS). Scavenger receptors (SRs) are a broad family of transmembrane receptors involved in a dysfunctional host–environment interaction through a reaction with reactive oxygen species (ROS) production. Objective: We hypothesized possible roles of two major SRs in CRS pathology that can translate to clinical phenotypes or histological subtypes: lectin-like oxidized low-density lipoproteins (LDL) receptor-1 (LOX-1) and scavenger receptor class B type 1 (SR-B1). Patients and Methods: We collected ethmoid sinus mucosa specimens and blood samples from patients with CRS with nasal polyps (CRSwNP; n = 31) or CRS without NP (CRSsNP; n = 13) and 19 control subjects. We performed an RT-PCR analysis, ELISA assay, and immunostaining to determine the expressions and distributions of LOX-1 and SR-B1. Results: The CRSwNP group showed a significant increase in LOX-1 mRNA expression compared to the control group. There was no significant difference in SR-B1 mRNA levels among the three groups. The LOX-1 mRNA levels were positively correlated with the sinus computed tomography (CT) scores. Sinus tissue, but not serum samples, showed elevated concentrations of LOX-1 protein in the CRSwNP group versus the control group. The LOX-1 protein distribution was localized in inflammatory cells and vascular endothelial cells. Conclusion: LOX-1 is a major receptor for oxidized low-density lipoprotein produced by oxidative stress. This is the first study to report alterations in LOX-1 expression and production triggered by persistent inflammatory processes in CRSwNP patients. Our findings reveal complex but important roles for SRs that may contribute to the onset of different CRS phenotypes. Full article

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

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12 pages, 1043 KiB

Open AccessArticle

Thyroid Pathology in End-Stage Renal Disease Patients on Hemodialysis

by Laura Cotoi, Florin Borcan, Ioan Sporea, Daniela Amzar, Oana Schiller, Adalbert Schiller, Cristina A. Dehelean, Gheorghe Nicusor Pop, Andreea Borlea and Dana Stoian

Diagnostics 2020, 10(4), 245; https://doi.org/10.3390/diagnostics10040245 - 23 Apr 2020

Cited by 15 | Viewed by 4525

Abstract

Objectives: Chronic kidney disease is a rising cause of morbidity and mortality in developed countries, including end-stage renal disease (ESRD). The prevalence of thyroid comorbidities in persons with chronic kidney disease is documented higher than in normal population. The study aims to investigate [...] Read more.

Objectives: Chronic kidney disease is a rising cause of morbidity and mortality in developed countries, including end-stage renal disease (ESRD). The prevalence of thyroid comorbidities in persons with chronic kidney disease is documented higher than in normal population. The study aims to investigate the prevalence of morphological and functional thyroid disorders in patients with chronic kidney disease, with renal replacement therapy (hemodialysis). Methods: A cross-sectional study was performed on 123 consecutive patients with chronic kidney disease stage 5, on hemodialysis during a period of one month (May 2019–June 2020). All patients were enrolled for maintenance hemodialysis in B Braun Hemodialysis Center Timisoara and were examined on conventional 2B ultrasound. Thyroid blood tests were done, including serum free thyroxin (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) at the time of starting hemodialysis. Results: We evaluated 123 patients (male to female ratio 70/53) mean age 62.2 ± 11.01, mostly above 65 years old, enrolled in the end-stage renal disease program, on renal replacement therapy. From the cohort, 76/123 presented thyroid disease, including autoimmune hypothyroidism, nodular goiter or thyroid cancer. Among them, 63 patients presented nodular goiter, including 3 thyroid cancers, confirmed by surgery and histopathological result, 22 patients had thyroid autoimmune disease. The serum thyroid-stimulating hormone levels found in the cohort was 3.36 ± 2.313 mUI/mL, which was in the normal laboratory reference range. The thyroid volume was 13 ± 7.18 mL. A single patient in the cohort presented Graves Basedow disease, under treatment and three patients present subclinical hyperthyroidism. We have found that thyroid disease risk is increased by 3.4-fold for the female gender and also the increase of body mass index (BMI) with one unit raises the risk of developing thyroid disease with 1.083 times (p = 0.018). Conclusion: To conclude, this study aimed to quantify the prevalence of thyroid disease in end-stage kidney disease population, especially nodular goiter, important for differential diagnosis in cases with secondary hyperparathyroidism. Thyroid autoimmune disease can be prevalent among these patients, as symptoms can overlap those of chronic disease and decrease the quality of life. We have found that thyroid disease has a high prevalence among patients with end-stage renal disease on hemodialysis. Thyroid goiter and nodules in ESRD patients were more prevalent than in the general population. Clinical surveillance and routine screening for thyroid disorders can improve the quality of life in these patients. Full article

(This article belongs to the Special Issue New Insights in Thyroid Diagnostics)

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16 pages, 5157 KiB

Open AccessReview

HRCT Patterns of Drug-Induced Interstitial Lung Diseases: A Review

by Giulio Distefano, Luigi Fanzone, Monica Palermo, Francesco Tiralongo, Salvatore Cosentino, Corrado Inì, Federica Galioto, Ada Vancheri, Sebastiano E. Torrisi, Letizia A. Mauro, Pietro V. Foti, Carlo Vancheri, Stefano Palmucci and Antonio Basile

Diagnostics 2020, 10(4), 244; https://doi.org/10.3390/diagnostics10040244 - 22 Apr 2020

Cited by 30 | Viewed by 14737

Abstract

Interstitial Lung Diseases (ILDs) represent a heterogeneous group of pathologies, which may be related to different causes. A low percentage of these lung diseases may be secondary to the administration of drugs or substances. Through the PubMed database, an extensive search was performed [...] Read more.

Interstitial Lung Diseases (ILDs) represent a heterogeneous group of pathologies, which may be related to different causes. A low percentage of these lung diseases may be secondary to the administration of drugs or substances. Through the PubMed database, an extensive search was performed in the fields of drug toxicity and interstitial lung disease. We have evaluated the different classes of drugs associated with pulmonary toxicity. Several different high resolution computed tomography (HRCT) patterns related to pulmonary drug toxicity have been reported in literature, and the most frequent ILDs patterns reported include Nonspecific Interstitial Pneumonia (NSIP), Usual Interstitial Pneumonia (UIP), Hypersensitivity Pneumonitis (HP), Organizing Pneumonia (OP), Acute Respiratory Distress Syndrome (ARDS), and Diffuse Alveolar Damage (DAD). Finally, from the electronic database of our Institute we have selected and commented on some cases of drug-induced lung diseases related to the administration of common drugs. As the imaging patterns are rarely specific, an accurate evaluation of the clinical history is required and a multidisciplinary approach—involving pneumologists, cardiologists, radiologists, pathologists, and rheumatologists—is recommended. Full article

(This article belongs to the Special Issue Clinical and Radiological Features of Interstitial Lung Diseases)

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23 pages, 382 KiB

Open AccessGuidelines

ISIDOG Recommendations Concerning COVID-19 and Pregnancy

by Francesca Donders, Risa Lonnée-Hoffmann, Aristotelis Tsiakalos, Werner Mendling, José Martinez de Oliveira, Philippe Judlin, Fengxia Xue, Gilbert G. G. Donders and ISIDOG COVID-19 Guideline Workgroup

Diagnostics 2020, 10(4), 243; https://doi.org/10.3390/diagnostics10040243 - 22 Apr 2020

Cited by 76 | Viewed by 29394

Abstract

Providing guidelines to health care workers during a period of rapidly evolving viral pandemic infections is not an easy task, but it is extremely necessary in order to coordinate appropriate action so that all patients will get the best possible care given the [...] Read more.

Providing guidelines to health care workers during a period of rapidly evolving viral pandemic infections is not an easy task, but it is extremely necessary in order to coordinate appropriate action so that all patients will get the best possible care given the circumstances they are in. With these International Society of Infectious Disease in Obstetrics and Gynecology (ISIDOG) guidelines we aim to provide detailed information on how to diagnose and manage pregnant women living in a pandemic of COVID-19. Pregnant women need to be considered as a high-risk population for COVID-19 infection, and if suspected or proven to be infected with the virus, they require special care in order to improve their survival rate and the well-being of their babies. Both protection of healthcare workers in such specific care situations and maximal protection of mother and child are envisioned. Full article

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

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9 pages, 578 KiB

Open AccessArticle

High-Sensitivity Troponin I and Creatinine Kinase-Myocardial Band in Screening for Myocardial Injury in Patients with Carbon Monoxide Poisoning

by June-Sung Kim, Byuk Sung Ko, Chang Hwan Sohn, Youn-Jung Kim and Won Young Kim

Diagnostics 2020, 10(4), 242; https://doi.org/10.3390/diagnostics10040242 - 21 Apr 2020

Cited by 10 | Viewed by 3788

Abstract

Myocardial dysfunction due to acute carbon monoxide (CO) poisoning is common and associated with poor outcomes. The role of cardiac markers, including creatine kinase-myocardial band (CK-MB), high-sensitivity troponin I (hsTnI), and brain natriuretic peptide (BNP), in identifying patients with CO-induced cardiomyopathy were evaluated. [...] Read more.

Myocardial dysfunction due to acute carbon monoxide (CO) poisoning is common and associated with poor outcomes. The role of cardiac markers, including creatine kinase-myocardial band (CK-MB), high-sensitivity troponin I (hsTnI), and brain natriuretic peptide (BNP), in identifying patients with CO-induced cardiomyopathy were evaluated. This single-center, retrospective cohort study included 905 consecutive adult patients in the CO poisoning registry from February 2009 to December 2019. Cardiomyopathy was defined as any abnormality on transthoracic echocardiography (TTE), including left ventricular systolic and diastolic dysfunction, right ventricular dysfunction, and wall motion abnormalities. The areas under receiver operating curves (AUCs) for biomarkers were compared. Of the 850 included patients, 101 (11.9%) had CO-induced cardiomyopathy. Initial and peak hsTnI and CK-MB concentrations, and initial BNP concentrations were significantly higher in patients with than without cardiomyopathy (all P-values < 0.01), but the AUCs were higher for hsTnI (0.894) and CK-MB (0.864) than for BNP (0.796). Initial TnI > 0.01 ng/mL and CK-MB > 1.5 ng/mL each had 95% sensitivity and 97% negative predictive value for CO-induced cardiomyopathy. Higher hsTnI or CK-MB levels on admission can identify patients at high-risk of CO-induced cardiomyopathy and can be a screening tool for CO poisoning. Full article

(This article belongs to the Special Issue Role of Imaging Modalities in the Evaluation of Nonischemic Cardiomyopathy)

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11 pages, 1665 KiB

Open AccessArticle

Fast Phase-Contrast Cine MRI for Assessing Intracranial Hemodynamics and Cerebrospinal Fluid Dynamics

by Naoki Ohno, Tosiaki Miyati, Tomohiro Noda, Noam Alperin, Takashi Hamaguchi, Masako Ohno, Tatsuhiko Matsushita, Mitsuhito Mase, Toshifumi Gabata and Satoshi Kobayashi

Diagnostics 2020, 10(4), 241; https://doi.org/10.3390/diagnostics10040241 - 21 Apr 2020

Cited by 15 | Viewed by 3927

Abstract

We propose fast phase-contrast cine magnetic resonance imaging (PC-cine MRI) to allow breath-hold acquisition, and we compared intracranial hemo- and hydrodynamic parameters obtained during breath holding between full inspiration and end expiration. On a 3.0 T MRI, using electrocardiogram (ECG)-synchronized fast PC-cine MRI [...] Read more.

We propose fast phase-contrast cine magnetic resonance imaging (PC-cine MRI) to allow breath-hold acquisition, and we compared intracranial hemo- and hydrodynamic parameters obtained during breath holding between full inspiration and end expiration. On a 3.0 T MRI, using electrocardiogram (ECG)-synchronized fast PC-cine MRI with parallel imaging, rectangular field of view, and segmented k-space, we obtained velocity-mapped phase images at the mid-C2 level with different velocity encoding for transcranial blood flow and cerebrospinal-fluid (CSF) flow. Next, we calculated the peak-to-peak amplitudes of cerebral blood flow (ΔCBF), cerebral venous outflow, intracranial volume change, CSF pressure gradient (ΔPG), and intracranial compliance index. These parameters were compared between the proposed and conventional methods. Moreover, we compared these parameters between different utilized breath-hold maneuvers (inspiration, expiration, and free breathing). All parameters derived from the fast PC method agreed with those from the conventional method. The ΔPG was significantly higher during full inspiration breath holding than at the end of expiration and during free breathing. The proposed fast PC-cine MRI reduced scan time (within 30 s) with good agreement with conventional methods. The use of this method also makes it possible to assess the effects of respiration on intracranial hemo- and hydrodynamics. Full article

(This article belongs to the Special Issue Brain Imaging/Neuroimaging)

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17 pages, 2709 KiB

Open AccessArticle

MicroRNA Expression Profile Changes after Cardiopulmonary Bypass and Ischemia/Reperfusion-Injury in a Porcine Model of Cardioplegic Arrest

by Attila Kiss, Stefan Heber, Anne-Margarethe Kramer, Matthias Hackl, Susanna Skalicky, Seth Hallström, Bruno K. Podesser and David Santer

Diagnostics 2020, 10(4), 240; https://doi.org/10.3390/diagnostics10040240 - 21 Apr 2020

Cited by 9 | Viewed by 3479

Abstract

Identification of microRNAs (miRNA) associated with cardiopulmonary bypass, cardiac arrest and subsequent myocardial ischemia/reperfusion may unravel novel therapeutic targets and biomarkers. The primary aim of the present study was to investigate the effects of cardiopulmonary bypass and temperature of cardioplegic arrest on myocardial [...] Read more.

Identification of microRNAs (miRNA) associated with cardiopulmonary bypass, cardiac arrest and subsequent myocardial ischemia/reperfusion may unravel novel therapeutic targets and biomarkers. The primary aim of the present study was to investigate the effects of cardiopulmonary bypass and temperature of cardioplegic arrest on myocardial miRNA profile in pigs’ left ventricular tissue. We employed next-generation sequencing to analyse miRNA profiles in the following groups: (1) hearts were arrested with antegrade warm St Thomas Hospital No. 2 (STH2) cardioplegia (n = 5; STH2-warm, 37 °C) and (2) cold STH2 (n = 6; STH2-cold, 4 °C) cardioplegia. Sixty min of ischemia was followed by 60 min of on-pump reperfusion with an additional 90 min of off-pump reperfusion. In addition, two groups without cardiac arrest (off-pump and on-pump group; n = 3, respectively) served as additional controls. STH2-warm and STH2-cold cardioplegia revealed no hemodynamic differences. In contrast, coronary venous creatine kinase-myocardial band (CK-MB) levels were significantly lower in pigs receiving STH2-warm cardioplegia (p < 0.05). Principal component analysis revealed that cardiopulmonary bypass and cardioplegic arrest markedly affected miRNAs in left ventricular tissue. Accordingly, ssc-miR-122, ssc-miR-10a-5p, ssc-miR-193a-3p, ssc-miR-499-3p, ssc-miR-374a-5p, ssc-miR-345-5p, ssc-miR-142-3p, ssc-miR-424-5p, ssc-miR-545-3p, ssc-miR-30b-5p, ssc-miR-145-5p, ssc-miR-374b-5p and ssc-miR-139-3p were differently regulated by cardiopulmonary bypass (false discovery rate (FDR) < 0.05 versus off-pump group). However, only ssc-miR-451 was differently expressed between STH2-warm and STH2-cold (FDR < 0.05). These data demonstrate for the first time that cardiopulmonary bypass and temperature of cardioplegic solution affected the expression of miRNAs in left ventricular tissue. In conclusion, specific miRNAs are potential therapeutic targets for limiting ischemia-reperfusion injury in patients undergoing cardiac surgery. Full article

(This article belongs to the Special Issue Animal Models for Studying and Screening Human Diseases)

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12 pages, 885 KiB

Open AccessArticle

Chromatographic Detection of 8-Hydroxy-2′-Deoxyguanosine in Leukocytes of Asbestos Exposed Workers for Assessing Past and Recent Carcinogen Exposures

by Filippo Cellai, Stefano Bonassi, Alfonso Cristaudo, Alessandra Bonotti, Monica Neri, Marcello Ceppi, Marco Bruzzone, Mirta Milić, Armelle Munnia and Marco Peluso

Diagnostics 2020, 10(4), 239; https://doi.org/10.3390/diagnostics10040239 - 21 Apr 2020

Cited by 1 | Viewed by 4054

Abstract

Asbestos fibers include a group of silicate minerals that occur in the environment and are widely employed in occupational settings. Asbestos exposure has been associated to various chronic diseases; such as pulmonary fibrosis; mesothelioma; and lung cancer; often characterized by a long period [...] Read more.

Asbestos fibers include a group of silicate minerals that occur in the environment and are widely employed in occupational settings. Asbestos exposure has been associated to various chronic diseases; such as pulmonary fibrosis; mesothelioma; and lung cancer; often characterized by a long period of latency. Underlying mechanisms that are behind the carcinogenic effect of asbestos have not been fully clarified. Therefore; we have conducted an epidemiological study to evaluate the relationship between 8-hydroxy-2′-deoxyguanosine (8-oxodG), one of the most reliable biomarkers of oxidative stress and oxidative DNA damage; and asbestos exposure in the peripheral blood of residents in Tuscany and Liguria regions; Italy; stratified by occupational exposure to this carcinogen. Levels of 8-oxodG were expressed such as relative adduct labeling (RAL); the frequency of 8-oxodG per 10⁵ deoxyguanosine was significantly higher among exposed workers with respect to the controls; i.e., 3.0 ± 0.2 Standard Error (SE) in asbestos workers versus a value of 1.3 ± 0.1 (SE) in unexposed controls (p < 0.001). When the relationship with occupational history was investigated; significant higher levels of 8-oxodG were measured in current and former asbestos workers vs. healthy controls; 3.1 ± 0.3 (SE) and 2.9 ± 0.2 (SE), respectively. After stratification for occupational history; a significant 194% excess of adducts was found in workers with 10 or more years of past asbestos exposure (p < 0.001). 8-oxodG can be used for medical surveillance programs of cohorts of workers with past and recent exposures to carcinogens for the identification of subjects requiring a more intense clinical surveillance. Full article

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

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13 pages, 1504 KiB

Open AccessArticle

Grip Strength: A Useful Marker for Composite Hepatic Events in Patients with Chronic Liver Diseases

by Kazunori Yoh, Hiroki Nishikawa, Hirayuki Enomoto, Yoshinori Iwata, Naoto Ikeda, Nobuhiro Aizawa, Takashi Nishimura, Hiroko Iijima and Shuhei Nishiguchi

Diagnostics 2020, 10(4), 238; https://doi.org/10.3390/diagnostics10040238 - 20 Apr 2020

Cited by 14 | Viewed by 3022

Abstract

Here we sought to clarify the prognostic impact of sarcopenia-related markers (grip strength (GS), muscle mass using bioimpedance analysis and patient quality of life as assessed by the 36-Item Short-Form Health Survey (SF36)) in patients with chronic liver diseases (CLDs, n = 411; [...] Read more.

Here we sought to clarify the prognostic impact of sarcopenia-related markers (grip strength (GS), muscle mass using bioimpedance analysis and patient quality of life as assessed by the 36-Item Short-Form Health Survey (SF36)) in patients with chronic liver diseases (CLDs, n = 411; 160 liver cirrhosis patients; median age, 64 years) on the incidence of composite hepatic events (CHEs). A GS decrease was defined as <26 kg in men and <18 kg in women, while a skeletal muscle mass index (SMI) decrease was defined as <7.0 kg/m² in men and <5.7 kg/m² in women based on the current guidelines. The physical and metal component summary scores on the SF36 were also included into the analysis. Sixty-two patients (15.1%) had the first incidence of CHEs. The three-year cumulative incidence rates of CHEs in patients with GS decrease or non-decrease were 24.51% and 12.44% (p = 0.0057). The three-year cumulative incidence rates of CHEs in patients with an SMI decrease or non-decrease were 19.65% and 12.99% (p = 0.0982). Multivariate analysis revealed that GS decrease (p = 0.0350) and prothrombin time (p = 0.0293) were significantly associated with the incidence of CHEs. In conclusion, GS can be an independent predictor for CHE development in patients with CLDs. Full article

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

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9 pages, 1180 KiB

Open AccessArticle

Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

by Jung-Ju Lee, Youngki Choi, Soie Chung, Dae Hyun Yoon, Seung Ho Choi, Sung-Min Kang, David Seo and Kyung-Il Park

Diagnostics 2020, 10(4), 237; https://doi.org/10.3390/diagnostics10040237 - 20 Apr 2020

Cited by 9 | Viewed by 4521

Abstract

The increasing prevalence of Alzheimer’s disease (AD) has become a global phenomenon presenting serious social and health challenges. For detecting early molecular changes in the disease, several techniques to measure varied species of amyloid beta in the peripheral blood have been recently developed, [...] Read more.

The increasing prevalence of Alzheimer’s disease (AD) has become a global phenomenon presenting serious social and health challenges. For detecting early molecular changes in the disease, several techniques to measure varied species of amyloid beta in the peripheral blood have been recently developed, but the efforts to associate them with cognitive assessments have yet to produce sufficient data. We prospectively collected participants from the consecutive population who visited our center for brain health screening. In total, 97 participants (F:M = 58:39) aged 69.4 ± 7.52 were assessed. Participants performed the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K), the clinical dementia rating (CDR), plasma oligomeric amyloid-β (OAβ) level tests, routine blood tests, ApoE genotype, and brain MRI. Among total population, 55.7% had a CDR of 0, and 40.2% had a CDR of 0.5. The results showed that word memory and word recall, and the total scores of the CERAD-K were negatively correlated with the plasma OAβ level. With a cut-off value of 0.78 ng/mL for the OAβ level and a −1.5 standard deviation of age/sex/education adjusted norms for the CERAD-K; naming, word memory, word recall, word recognition, and total score were significantly correlated with the OAβ level. No correlation between the OAβ level and mini-mental status examination was found. Our results demonstrate that the level of plasma OAβ was well correlated with the measure of cognitive function through the CERAD-K in the field data collected from consecutive populations. Studies on longitudinal comparisons with large cohorts will further validate the diagnostic value of plasma OAβ as a useful biomarker for screening AD and predicting progression. Full article

(This article belongs to the Special Issue Alzheimer’s Disease Pathophysiology)

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20 pages, 1956 KiB

Open AccessArticle

Postmortem Determination of Short-Term Markers of Hyperglycemia for the Purposes of Medicolegal Opinions

by Karolina Nowak, Tomasz Jurek and Marcin Zawadzki

Diagnostics 2020, 10(4), 236; https://doi.org/10.3390/diagnostics10040236 - 19 Apr 2020

Cited by 3 | Viewed by 2949

Abstract

Diabetes mellitus is classified as the epidemic of the 21st century. Due to the fact that acute carbohydrate metabolism disorders usually do not indicate morphological change, postmortem diagnosis is required to perform biochemical tests. The authors decided to evaluate the usefulness of determining [...] Read more.

Diabetes mellitus is classified as the epidemic of the 21st century. Due to the fact that acute carbohydrate metabolism disorders usually do not indicate morphological change, postmortem diagnosis is required to perform biochemical tests. The authors decided to evaluate the usefulness of determining glucose, lactate, acetone, β-hydroxybutyric acid (BHB), and 1,5-anhydroglucitol (1,5-AG) in postmortem blood/serum, urine, and vitreous humor (VH). Biological material was collected during autopsies. The study group consisted of 50 diabetics, while the control group consisted of 50 non-diabetics, who died a sudden death, with negative test results for the presence of ethyl alcohol and were not resuscitated before death. Statistical analysis was performed using the IBM SPSS Statistics 25 software package. The most statistically significant difference between the two groups was observed for mean 1,5-AG concentration. The authors found many correlations between the concentration of the examined markers in different materials, mainly between blood/serum and VH. The most suitable short-term glycemic marker in postmortem diagnosis is 1,5-AG. Diagnosis may be supported with determinations of acetone and BHB. For medicolegal assessment, the interpretation of the biochemical test results should comprise information on circumstances of death, medical history, results of other toxicological and histopathological tests, and autopsy report. Full article

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

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13 pages, 1777 KiB

Open AccessArticle

Choroidal Changes of Long-Term Type 1 Diabetic Patients without Retinopathy

by Elvira Orduna-Hospital, Lorena Perdices, Ana Sanchez-Cano, Javier Acha, Nicolás Cuenca and Isabel Pinilla

Diagnostics 2020, 10(4), 235; https://doi.org/10.3390/diagnostics10040235 - 19 Apr 2020

Cited by 10 | Viewed by 2810

Abstract

The aim of the study is to assess choroidal thickness (CT) and choroidal volume (CV) in 90 type 1 diabetes mellitus (DM1) patients with no diabetic retinopathy (DR) and 60 control eyes using spectral domain optical coherence tomography (SD-OCT) and swept source (SS)-OCT [...] Read more.

The aim of the study is to assess choroidal thickness (CT) and choroidal volume (CV) in 90 type 1 diabetes mellitus (DM1) patients with no diabetic retinopathy (DR) and 60 control eyes using spectral domain optical coherence tomography (SD-OCT) and swept source (SS)-OCT in the areas of the Early Treatment Diabetic Retinopathy Study (ETDRS). Mean ages were 42.93 ± 13.62 and 41.52 ± 13.05 years in the diabetic and control groups, respectively. Significant differences were obtained between both groups with Spectralis SD-OCT in all ETDRS areas and in the total CV, excluding the temporal perifoveal one. With Triton SS-OCT, statistically significant differences were obtained in the subfoveal CT and in the vertical areas. CT showed the same tendency with both OCTs, with greater CT and CV in the DM1 group than the mean values of the control group. To assess the influence of DM1 evolution in the CT modifications, DM1 patients were divided into Group 1, with less than 24 years of diagnosis, and Group 2, with ≥24 years of DM1 evolution. Using both OCTs, seven of the nine ETDRS areas and the CV had lower values in Group 2. CT and CV measured by OCT were higher in DM1 without DR. There is a choroidal thinning related to disease evolution in DM1. In patients with DM evolution greater than 24 years, the CT is statistically lower than in patients with less evolution of the disease. Full article

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

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10 pages, 1416 KiB

Open AccessArticle

Comparison of Four Commercial Kits for Isolation of Urinary Cell-Free DNA and Sample Storage Conditions

by Eun Young Lee, Eun-Ju Lee, Hana Yoon, Dong Hyeon Lee and Kwang Hyun Kim

Diagnostics 2020, 10(4), 234; https://doi.org/10.3390/diagnostics10040234 - 18 Apr 2020

Cited by 19 | Viewed by 5223

Abstract

Urinary cell-free DNA (cfDNA) is an attractive body fluid for liquid biopsy. In this study, we compared the efficiencies of four commercial kits for urinary cell-free DNA (cfDNA) isolation and of various sample storage conditions. Urinary cfDNA was isolated from 10 healthy individuals [...] Read more.

Urinary cell-free DNA (cfDNA) is an attractive body fluid for liquid biopsy. In this study, we compared the efficiencies of four commercial kits for urinary cell-free DNA (cfDNA) isolation and of various sample storage conditions. Urinary cfDNA was isolated from 10 healthy individuals using four commercial kits: QIAamp Circulating Nucleic Acid Kit (QC; Qiagen), MagMAX™ Cell-Free DNA Isolation Kit (MM; Applied Biosystems), Urine Cell-Free Circulating DNA Purification Midi Kit (NU; Norgen Biotek), and Quick-DNA™ Urine Kit (ZQ; Zymo Research). To assess the isolation efficiency, an Agilent 2100 Bioanalyzer with High Sensitivity DNA chips was used, and cfDNA yield was defined as the amount of cfDNA obtained from 1 mL of urine. MM and QC provided the highest cfDNA yield in the 50–300 bp range, and MM and NU gave the highest cfDNA yield in the 50–100 bp range. In particular, the NU kit was efficient for isolation of more fragmented cfDNA in the range of 50–100 bp with the lowest cellular genomic DNA contamination. ZQ had the best cost-efficiency for isolating the same amount of urinary cfDNA. Samples stored at −70 °C with the addition of 10 mM EDTA resulted in the highest cfDNA yield 3 months after sample collection. Full article

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

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25 pages, 4852 KiB

Open AccessReview

Epithelioid Cutaneous Mesenchymal Neoplasms: A Practical Diagnostic Approach

by Joon Hyuk Choi and Jae Y. Ro

Diagnostics 2020, 10(4), 233; https://doi.org/10.3390/diagnostics10040233 - 17 Apr 2020

Cited by 4 | Viewed by 8949

Abstract

Epithelioid cells are rounded or polygonal cells with abundant eosinophilic or clear cytoplasm and ovoid to round nuclei, superficially resembling epithelial cells. Cutaneous mesenchymal neoplasms composed predominantly or exclusively of epithelioid cells are relatively uncommon and can cause considerable diagnostic difficulties due to [...] Read more.

Epithelioid cells are rounded or polygonal cells with abundant eosinophilic or clear cytoplasm and ovoid to round nuclei, superficially resembling epithelial cells. Cutaneous mesenchymal neoplasms composed predominantly or exclusively of epithelioid cells are relatively uncommon and can cause considerable diagnostic difficulties due to overlapping histologic features among heterogeneous groups of tumors. Familiarity with practical diagnostic approaches and recognition of key histopathologic features are important for correct diagnosis and management. This review summarizes the histologic features of epithelioid cutaneous mesenchymal neoplasms and discusses their differential diagnoses from malignant melanomas and carcinomas. Full article

(This article belongs to the Special Issue Melanoma and Skin Cancer)

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7 pages, 1256 KiB

Open AccessCase Report

Diagnosis of Hourglass-Like Constriction Neuropathy of the Radial Nerve Using High-Resolution Magnetic Resonance Neurography: A Report of Two Cases

by Du Hwan Kim, Duk Hyun Sung and Min Cheol Chang

Diagnostics 2020, 10(4), 232; https://doi.org/10.3390/diagnostics10040232 - 17 Apr 2020

Cited by 9 | Viewed by 4778

Abstract

Hourglass-like constriction neuropathy is a neurological condition caused by fascicular constriction of one or more peripheral nerves, unrelated to intrinsic or extrinsic compression. It is often neglected in clinical practice, and its diagnosis is challenging. Here, we report two cases of hourglass-like constriction [...] Read more.

Hourglass-like constriction neuropathy is a neurological condition caused by fascicular constriction of one or more peripheral nerves, unrelated to intrinsic or extrinsic compression. It is often neglected in clinical practice, and its diagnosis is challenging. Here, we report two cases of hourglass-like constriction neuropathy in the radial nerve diagnosed using high-resolution magnetic resonance neurography (MRN). Two men, aged 47 and 19 years, developed sudden weakness in the left wrist and finger extensors. They were diagnosed with radial neuropathy between the left mid-humerus level and the elbow joint, using the electrodiagnostic test. To evaluate the cause of the nerve lesion and the lesion location, high-resolution MRN was performed. Patient 1 showed an hourglass-like constriction of the left posterior interosseous nerve within the epineurium of the left radial nerve, 8.9 cm proximal to the lateral epicondyle. Patient 2 showed two focal constrictions of the left radial nerve, 8.0 and 6.9 cm proximal to the lateral epicondyle, respectively, and distal to the radial groove. Additionally, bull’s eye signs were observed juxta-proximal to constrictions of the left radial nerve. The findings were indicative of hourglass-like constriction neuropathy. Both of the patients underwent surgery. However, at the 6-month follow-up, their motor weakness showed no improvement. MRN can be beneficial for diagnosing hourglass-like constriction neuropathy and locating the lesion. Full article

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

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9 pages, 197 KiB

Open AccessArticle

Artificial Intelligence in Radiology—Ethical Considerations

by Adrian P. Brady and Emanuele Neri

Diagnostics 2020, 10(4), 231; https://doi.org/10.3390/diagnostics10040231 - 17 Apr 2020

Cited by 68 | Viewed by 8806

Abstract

Artificial intelligence (AI) is poised to change much about the way we practice radiology in the near future. The power of AI tools has the potential to offer substantial benefit to patients. Conversely, there are dangers inherent in the deployment of AI in [...] Read more.

Artificial intelligence (AI) is poised to change much about the way we practice radiology in the near future. The power of AI tools has the potential to offer substantial benefit to patients. Conversely, there are dangers inherent in the deployment of AI in radiology, if this is done without regard to possible ethical risks. Some ethical issues are obvious; others are less easily discerned, and less easily avoided. This paper explains some of the ethical difficulties of which we are presently aware, and some of the measures we may take to protect against misuse of AI. Full article

(This article belongs to the Special Issue Artificial Intelligence in Diagnostics)

11 pages, 1003 KiB

Open AccessArticle

MicroRNA Profile of Patients with Chronic Limb-Threatening Ischemia

by Muzammil H. Syed, Abdelrahman Zamzam, Jason Valencia, Hamzah Khan, Shubha Jain, Krishna K. Singh, Rawand Abdin and Mohammad Qadura

Diagnostics 2020, 10(4), 230; https://doi.org/10.3390/diagnostics10040230 - 17 Apr 2020

Cited by 15 | Viewed by 3084

Abstract

Chronic limb-threatening ischemia (CLTI) results in devastating complications such as lower-limb amputations. In this study, a genome-wide plasma microRNAs (miRNA) sequencing was performed to identify miRNA(s) associated with CLTI. Blood samples were collected from early stage CLTI patients (ABI < 0.9) and non-PAD [...] Read more.

Chronic limb-threatening ischemia (CLTI) results in devastating complications such as lower-limb amputations. In this study, a genome-wide plasma microRNAs (miRNA) sequencing was performed to identify miRNA(s) associated with CLTI. Blood samples were collected from early stage CLTI patients (ABI < 0.9) and non-PAD controls (ABI ≥ 0.9) for 3 experiments: discovery phase (n = 23), confirmatory phase (n = 52) and validation phase (n = 20). In the discovery phase, next generation sequencing (NGS) was used to identify miRNA circulating in the plasma CLTI (n = 13) patients, compared to non-PAD controls (n = 10). Two down-regulated miRNAs (miRNA-6843-3p and miRNA-6766-5p) and three upregulated miRNAs (miRNA-1827, miRNA-320 and miRNA-98-3p) were identified (≥2-fold change). In the confirmatory phase, these 5 deregulated miRNAs were further investigated in non-PAD (n = 21) and CTLI (n = 31) patients using qRT-PCR. Only miRNA-1827 was found to be significantly upregulated (≥3-fold, p-value < 0. 001) in the CLTI group. Lastly, to minimize the influence of confounding factors, miRNA-1827 plasma levels were validated in a third cohort of CLTI patients (n = 10) matched to non-PAD controls (n = 10). Our analysis demonstrated that miRNA-1827 expression was increased in the CLTI cohort (≥2-folds, p-value < 0.001). In summary, circulating miRNA-1827 is significantly elevated in patients with CLTI. Full article

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

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14 pages, 4184 KiB

Open AccessArticle

Geographical Accessibility to Glucose-6-Phosphate Dioxygenase Deficiency Point-of-Care Testing for Antenatal Care in Ghana

by Desmond Kuupiel, Kwame M. Adu, Vitalis Bawontuo, Duncan A. Adogboba, Paul K. Drain, Mosa Moshabela and Tivani P. Mashamba-Thompson

Diagnostics 2020, 10(4), 229; https://doi.org/10.3390/diagnostics10040229 - 16 Apr 2020

Cited by 18 | Viewed by 6204

Abstract

Background: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency screening test is essential for malaria treatment, control, and elimination programs. G6PD deficient individuals are at high risk of severe hemolysis when given anti-malarial drugs such as primaquine, quinine, other sulphonamide-containing medicines, and chloroquine, which has recently been [...] Read more.

Background: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency screening test is essential for malaria treatment, control, and elimination programs. G6PD deficient individuals are at high risk of severe hemolysis when given anti-malarial drugs such as primaquine, quinine, other sulphonamide-containing medicines, and chloroquine, which has recently been shown to be potent for the treatment of coronavirus disease (COVID-19). We evaluated the geographical accessibility to POC testing for G6PD deficiency in Ghana, a malaria-endemic country. Methods: We obtained the geographic information of 100 randomly sampled clinics previously included in a cross-sectional survey. We also obtained the geolocated data of all public hospitals providing G6PD deficiency testing services in the region. Using ArcGIS 10.5, we quantified geographical access to G6PD deficiency screening test and identified clinics as well as visualize locations with poor access for targeted improvement. The travel time was estimated using an assumed speed of 20 km per hour. Findings: Of the 100 clinics, 58% were Community-based Health Planning and Services facilities, and 42% were sub-district health centers. The majority (92%) were Ghana Health Service facilities, and the remaining 8% were Christian Health Association of Ghana facilities. Access to G6PD deficiency screening test was varied across the districts, and G6PD deficiency screening test was available in all eight public hospitals. This implies that the health facility-to-population ratio for G6PD deficiency testing service was approximately 1:159,210 (8/1,273,677) population. The spatial analysis quantified the current mean distance to a G6PD deficiency testing service from all locations in the region to be 34 ± 14 km, and travel time (68 ± 27 min). The estimated mean distance from a clinic to a district hospital for G6PD deficiency testing services was 15 ± 11 km, and travel time (46 ± 33 min). Conclusion: Access to POC testing for G6PD deficiency in Ghana was poor. Given the challenges associated with G6PD deficiency, it would be essential to improve access to G6PD deficiency POC testing to facilitate administration of sulphadoxine-pyrimethamine to pregnant women, full implementation of the malaria control program in Ghana, and treatment of COVID-19 patients with chloroquine in malaria-endemic countries. To enable the World Health Organization include appropriate G6PD POC diagnostic tests in its list of essential in-vitro diagnostics for use in resource-limited settings, we recommend a wider evaluation of available POC diagnostic tests for G6PD deficiency, particularly in malaria-endemic countries. Full article

(This article belongs to the Special Issue Implementation and Scale Up of Point of Care (POC) Diagnostics in Resource-Limited Settings)

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17 pages, 2766 KiB

Open AccessArticle

Identification of the Potential Prognostic Markers from the miRNA-lncRNA-mRNA Interactions for Metastatic Renal Cancer via Next-Generation Sequencing and Bioinformatics

by I-Jeng Yeh, Kuan-Ting Liu, Jheng-Heng Shen, Yen-Hung Wu, Yao-Hua Liu, Meng-Chi Yen and Po-Lin Kuo

Diagnostics 2020, 10(4), 228; https://doi.org/10.3390/diagnostics10040228 - 16 Apr 2020

Cited by 14 | Viewed by 3193

Abstract

The survival rate in patients with metastatic renal cell carcinoma (RCC) is low. In addition, metastatic RCC resists traditional treatment. Therefore, identification of novel biomarkers, signaling pathways, and therapeutic targets is an important issue. The aim of the present study is to identify [...] Read more.

The survival rate in patients with metastatic renal cell carcinoma (RCC) is low. In addition, metastatic RCC resists traditional treatment. Therefore, identification of novel biomarkers, signaling pathways, and therapeutic targets is an important issue. The aim of the present study is to identify novel prognostic markers from the miRNA-mediated network for the regulation of metastasis of RCC. To address this issue, the RNA of human RCC cell lines, 786-O and ACHN, derived from primary and metastatic sites, respectively, were collected and subjected to RNA sequencing and small RNA sequencing. The bioinformatic analysis revealed that the pathways of the genes with different expressions were related to tumor progression, and identified miRNA and miRNA-long non-coding RNA (lncRNA) interactions, and mRNA. The results revealed that the expressions of seven miRNAs were associated with the overall survival rate of patients with RCC. Furthermore, the expressions of two lncRNA and three protein-coding genes (mRNA) were significantly associated with the increased or decreased disease-free survival rate. Although the detailed regulatory mechanism between miRNAs and targeted genes was not fully understood, our findings present novel prognostic markers and novel insight on miRNA-mediated pathways for metastatic RCC. Full article

(This article belongs to the Special Issue Next-Generation Sequencing in Tumor Diagnosis and Treatment)

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12 pages, 1388 KiB

Open AccessArticle

Increased E2F1 mRNA and miR-17-5p Expression Is Correlated to Invasiveness and Proliferation of Pituitary Neuroendocrine Tumours

by Araceli García-Martínez, Beatriz López-Muñoz, Carmen Fajardo, Rosa Cámara, Cristina Lamas, Sandra Silva-Ortega, Ignacio Aranda and Antonio Picó

Diagnostics 2020, 10(4), 227; https://doi.org/10.3390/diagnostics10040227 - 16 Apr 2020

Cited by 11 | Viewed by 3023

Abstract

miR-17-5p and E2F1 have been described as deregulated in cancer, but they have scarcely been studied in pituitary neuroendocrine tumours (PitNETs). This study evaluates the relationship of E2F1 and miR-17-5p with the invasiveness and proliferation of PitNETs. In this cross-sectional descriptive study, we [...] Read more.

miR-17-5p and E2F1 have been described as deregulated in cancer, but they have scarcely been studied in pituitary neuroendocrine tumours (PitNETs). This study evaluates the relationship of E2F1 and miR-17-5p with the invasiveness and proliferation of PitNETs. In this cross-sectional descriptive study, we evaluated the expression of E2F1, MYC, and miR-17-5p by quantitative real time PCR analysis in 60 PitNETs: 29 gonadotroph (GT), 15 functioning somatotroph (ST), and 16 corticotroph (CT) tumours, of which 8 were silent (sCT). The clinical data were collected from the Spanish Molecular Register of Pituitary Adenomas (REMAH) database. We defined invasiveness according to the Knosp classification and proliferation according to a molecular expression of Ki-67 ≥ 2.59. E2F1 was more expressed in invasive than in non-invasive tumours in the whole series (p = 0.004) and in STs (p = 0.01). In addition, it was overexpressed in the silent subtypes (GTs and sCTs; all macroadenomas) and normoexpressed in the functioning ones (fCTs and STs; some microadenomas). miR-17-5p was more expressed in proliferative than in non-proliferative tumours (p = 0.041) in the whole series but not by subtypes. Conclusions: Our study suggests that in PitNETs, E2F1 could be a good biomarker of invasiveness, and miR-17-5p of proliferation, helping the clinical management of these tumours. Full article

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

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9 pages, 453 KiB

Open AccessArticle

Fusion and Healing Prediction in Posterolateral Spinal Fusion Using ¹⁸F-Sodium Fluoride-PET/CT

by Caius M. Constantinescu, Michael K. Jacobsen, Oke Gerke, Mikkel Ø. Andersen and Poul F. Høilund-Carlsen

Diagnostics 2020, 10(4), 226; https://doi.org/10.3390/diagnostics10040226 - 16 Apr 2020

Cited by 2 | Viewed by 3633

Abstract

This study measures the total graft of ¹⁸F-sodium fluoride (NaF) uptake in non-instrumented posterolateral lumbar fusion (niPLF) patients one month after surgery and correlates it with the difference in the clinical findings between the baseline and one year after surgery. The walking [...] Read more.

This study measures the total graft of ¹⁸F-sodium fluoride (NaF) uptake in non-instrumented posterolateral lumbar fusion (niPLF) patients one month after surgery and correlates it with the difference in the clinical findings between the baseline and one year after surgery. The walking distance (WLK-D), visual analog scale of back pain (VAS-B), VAS score of leg pain (VAS-L), tandem test (TAN), Oswestry Disability Index questionnaire (ODI), and European Quality of Life-5 Dimensions questionnaire (EQ-5D) were assessed before surgery and one year after. The graft NaF uptake was analyzed quantitatively with a fixed threshold algorithm resulting in the total graft uptake (SUVtotal) and partial volume corrected SUVtotal (cSUVtotal). Only 4 out of 18 patients experienced fusion; they had an insignificantly lower median total graft uptakes, i.e., 1178 SUVtotal vs. 1224 SUVtotal (p = 0.73) and 1282 cSUVtotal vs. 1231 cSUVtotal (p = 0.35), respectively. Similarly, fused patients experienced insignificantly larger pain decreases, i.e., median VAS-B 4.3 vs. 3.8 (p = 0.92) and VAS-L −6.4 vs. −4.4 (p = 0.2). We found an insignificant trend for a lower NaF uptake and less pain in fused patients. The NaF uptake did not correlate with the chronological change in the clinical parameters. Full article

(This article belongs to the Special Issue Positron Emission Tomography (PET) Imaging for Therapy Monitoring)

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11 pages, 433 KiB

Open AccessArticle

Quantification of Ground Glass Opacities Can Be Useful to Describe Disease Activity in Systemic Sclerosis

by Domenico Sambataro, Gianluca Sambataro, Francesca Pignataro, Wanda Maglione, Lorenzo Malatino, Carlo Vancheri, Michele Colaci and Nicoletta Del Papa

Diagnostics 2020, 10(4), 225; https://doi.org/10.3390/diagnostics10040225 - 16 Apr 2020

Cited by 7 | Viewed by 2737

Abstract

Interstitial lung disease (ILD) is the main cause of death in systemic sclerosis (SSc) patients. Usually, patients have lung involvement characterized by ground glass opacities (GGOs), but honeycombing (HC) is also possible. The Wells score is a semi-quantitative index, which is able to [...] Read more.

Interstitial lung disease (ILD) is the main cause of death in systemic sclerosis (SSc) patients. Usually, patients have lung involvement characterized by ground glass opacities (GGOs), but honeycombing (HC) is also possible. The Wells score is a semi-quantitative index, which is able to assess ILD by distinguishing its main components. The aim of this work is to evaluate the Wells score in relation to the disease activity (DA) index. We enrolled 40 consecutive SSc-ILD patients (26 diffuse cutaneous form, dcSSc, and 14 limited form, lcSSc). All patients were evaluated by the European Scleroderma Study Group (ESSG) index, high-resolution computed tomography, transthoracic echocardiogram, pulmonary function tests (PTSs), and nailfold videocapillaroscopy for the number of microhemorrhages (NEMO) score. In our study, the total extent of ILD (TE-ILD), fibrosis and GGOs correlated with dyspnea (p = 0.03, 0.01 and 0.01 respectively), but not with the ESSG index. Considering only the dcSSc patients, TE-ILD and GGOs correlated with the ESSG index (r = 0.5 p = 0.009), while fibrosis grade correlated with disease duration and systolic pulmonary artery pressure. In conclusion, our data suggest that GGO correlates with DA, while fibrosis may be a sign of disease damage. The quantification of pulmonary involvement using the Wells score can be a useful tool for assessing the appropriate treatment in SSc patients. Full article

(This article belongs to the Special Issue Clinical and Radiological Features of Interstitial Lung Diseases)

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3 pages, 581 KiB

Open AccessEditorial

Combining Point-of-Care Diagnostics and Internet of Medical Things (IoMT) to Combat the COVID-19 Pandemic

by Ting Yang, Mattia Gentile, Ching-Fen Shen and Chao-Min Cheng

Diagnostics 2020, 10(4), 224; https://doi.org/10.3390/diagnostics10040224 - 16 Apr 2020

Cited by 88 | Viewed by 11447

Abstract

The current standard testing method for screening coronavirus disease 2019 (COVID-19) is through reverse real-time PCR assay (rRT-PCR), a common molecular-based assay that requires an average of four to six hours to provide results [...] Full article

(This article belongs to the Collection Virus Diagnostic Methods and Techniques: Learning from the COVID-19 Global Outbreak)

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26 pages, 3519 KiB

Open AccessReview

Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications

by Maria-Eliza Nedu, Mihaela Tertis, Cecilia Cristea and Alexandru Valentin Georgescu

Diagnostics 2020, 10(4), 223; https://doi.org/10.3390/diagnostics10040223 - 15 Apr 2020

Cited by 34 | Viewed by 12759

Abstract

Methylene blue and proflavine are fluorescent dyes used to stain nucleic acid from the molecular level to the tissue level. Already clinically used for sentinel node mapping, detection of neuroendocrine tumors, methemoglobinemia, septic shock, ifosfamide-induced encephalopathy, and photodynamic inactivation of RNA viruses, the [...] Read more.

Methylene blue and proflavine are fluorescent dyes used to stain nucleic acid from the molecular level to the tissue level. Already clinically used for sentinel node mapping, detection of neuroendocrine tumors, methemoglobinemia, septic shock, ifosfamide-induced encephalopathy, and photodynamic inactivation of RNA viruses, the antimicrobial, anti-inflammatory, and antioxidant effect of methylene blue has been demonstrated in different in vitro and in vivo studies. Proflavine was used as a disinfectant and bacteriostatic agent against many gram-positive bacteria, as well as a urinary antiseptic involved in highlighting cell nuclei. At the tissue level, the anti-inflammatory effects of methylene blue protect against pulmonary, renal, cardiac, pancreatic, ischemic-reperfusion lesions, and fevers. First used for their antiseptic and antiviral activity, respectively, methylene blue and proflavine turned out to be excellent dyes for diagnostic and treatment purposes. In vitro and in vivo studies demonstrated that both dyes are efficient as perfusion and tissue tracers and permitted to evaluate the minimal efficient concentration in different species, as well as their pharmacokinetics and toxicity. This review aims to identify the optimal concentrations of methylene blue and proflavine that can be used for in vivo experiments to highlight the vascularization of the skin in the case of a perforasome (both as a tissue tracer and in vascular mapping), as well as their effects on tissues. This review is intended to be a comparative and critical presentation of the possible applications of methylene blue (MB) and proflavine (PRO) in the surgical field, and the relevant biomedical findings from specialized literature to date are discussed as well. Full article

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

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Diagnostics, Volume 10, Issue 4 (April 2020) – 75 articles

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