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Diagnostics, Volume 11, Issue 11 (November 2021) – 229 articles

Cover Story (view full-size image): We show that nuclease-based enzymatic cleavage of oligonucleotide probes works as an intrinsic amplification module, powering the sensitive detection of pathogens expressing a target nuclease. Ultrasensitive and specific detection of S. aureus bacteria was achieved in a lateral flow strip by targeting the S. aureus nuclease (MN) using chemically modified oligonucleotide substrates. Importantly, we achieved significant reduction of S. aureus bacteria cultures to 6 hours, proving the feasibility and potential of this technology to be extended to other pathogens. View this paper.
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20 pages, 798 KiB  
Guidelines
Best Practice Recommendations for the Implementation of a Digital Pathology Workflow in the Anatomic Pathology Laboratory by the European Society of Digital and Integrative Pathology (ESDIP)
by Filippo Fraggetta, Vincenzo L’Imperio, David Ameisen, Rita Carvalho, Sabine Leh, Tim-Rasmus Kiehl, Mircea Serbanescu, Daniel Racoceanu, Vincenzo Della Mea, Antonio Polonia, Norman Zerbe and Catarina Eloy
Diagnostics 2021, 11(11), 2167; https://doi.org/10.3390/diagnostics11112167 - 22 Nov 2021
Cited by 65 | Viewed by 10713
Abstract
The interest in implementing digital pathology (DP) workflows to obtain whole slide image (WSI) files for diagnostic purposes has increased in the last few years. The increasing performance of technical components and the Food and Drug Administration (FDA) approval of systems for primary [...] Read more.
The interest in implementing digital pathology (DP) workflows to obtain whole slide image (WSI) files for diagnostic purposes has increased in the last few years. The increasing performance of technical components and the Food and Drug Administration (FDA) approval of systems for primary diagnosis led to increased interest in applying DP workflows. However, despite this revolutionary transition, real world data suggest that a fully digital approach to the histological workflow has been implemented in only a minority of pathology laboratories. The objective of this study is to facilitate the implementation of DP workflows in pathology laboratories, helping those involved in this process of transformation to identify: (a) the scope and the boundaries of the DP transformation; (b) how to introduce automation to reduce errors; (c) how to introduce appropriate quality control to guarantee the safety of the process and (d) the hardware and software needed to implement DP systems inside the pathology laboratory. The European Society of Digital and Integrative Pathology (ESDIP) provided consensus-based recommendations developed through discussion among members of the Scientific Committee. The recommendations are thus based on the expertise of the panel members and on the agreement obtained after virtual meetings. Prior to publication, the recommendations were reviewed by members of the ESDIP Board. The recommendations comprehensively cover every step of the implementation of the digital workflow in the anatomic pathology department, emphasizing the importance of interoperability, automation and tracking of the entire process before the introduction of a scanning facility. Compared to the available national and international guidelines, the present document represents a practical, handy reference for the correct implementation of the digital workflow in Europe. Full article
(This article belongs to the Special Issue Digital Pathology: Records of Successful Implementations)
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<p>Differences among analog and the digital workflows. Credit: created with BioRender.</p>
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16 pages, 3546 KiB  
Review
Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: Role of the Radiologist and Oncologist in the Era of Precision Medicine
by Federica Vernuccio, Carlo Messina, Valeria Merz, Roberto Cannella and Massimo Midiri
Diagnostics 2021, 11(11), 2166; https://doi.org/10.3390/diagnostics11112166 - 22 Nov 2021
Cited by 9 | Viewed by 3726
Abstract
The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. [...] Read more.
The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. An adequate staging of pancreatic ductal adenocarcinoma and re-assessment of the tumor after neoadjuvant therapy allows the multidisciplinary team to choose the most appropriate treatment for the patient. This review article discusses advancement in the molecular basis of pancreatic ductal adenocarcinoma, diagnostic tools available for staging and tumor response assessment, and management of resectable or borderline resectable pancreatic cancer. Full article
(This article belongs to the Special Issue Advances in Diagnostic Medical Imaging)
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<p>A 57-year-old man who came to the emergency department for jaundice and abdominal pain. (<b>a</b>,<b>b</b>) US detected a mass in the pancreatic head (white arrow) causing upstream dilatation of the common bile duct (white arrowhead); (<b>c</b>,<b>d</b>) Pancreatic CT scan confirmed the presence of mass in the pancreatic head (*) that caused encasement of the gastroduodenal artery (black arrow) as well as encasement and narrowing of the superior mesenteric-portal venous confluence (black arrowhead), the superior mesenteric vein, and the portal vein.</p>
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<p>A 61-year-old man with non-resectable PDAC. Pancreatic CT scan on (<b>a</b>) arterial and (<b>b</b>) portal venous phases shows the presence of a biliary stent (black arrowhead) and a pancreatic mass (*) causing encasement of both superior mesenteric artery (black arrow) and vein (white arrow). The patient commenced modified FOLFIRINOX regimen at diagnosis. However, after 6 months, (<b>c</b>) liver MRI on diffusion weighted imaging showed appearance of liver metastasis in segment IV (arrowhead in c).</p>
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15 pages, 2786 KiB  
Article
Serum Organ-Specific Anti-Heart and Anti-Intercalated Disk Autoantibodies as New Autoimmune Markers of Cardiac Involvement in Systemic Sclerosis: Frequency, Clinical and Prognostic Correlates
by Alida Linda Patrizia Caforio, Giacomo De Luca, Anna Baritussio, Mara Seguso, Nicoletta Gallo, Elisa Bison, Maria Grazia Cattini, Elena Pontara, Luna Gargani, Alessia Pepe, Corrado Campochiaro, Mario Plebani, Sabino Iliceto, Giovanni Peretto, Antonio Esposito, Lorenzo Tofani, Alberto Moggi-Pignone, Lorenzo Dagna, Renzo Marcolongo, Marco Matucci-Cerinic and Cosimo Bruniadd Show full author list remove Hide full author list
Diagnostics 2021, 11(11), 2165; https://doi.org/10.3390/diagnostics11112165 - 22 Nov 2021
Cited by 13 | Viewed by 2930
Abstract
Background: Heart involvement (HInv) in systemic sclerosis (SSc) may relate to myocarditis and is associated with poor prognosis. Serum anti-heart (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific markers of isolated autoimmune myocarditis. We assessed frequencies, clinical correlates, and prognostic impacts [...] Read more.
Background: Heart involvement (HInv) in systemic sclerosis (SSc) may relate to myocarditis and is associated with poor prognosis. Serum anti-heart (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific markers of isolated autoimmune myocarditis. We assessed frequencies, clinical correlates, and prognostic impacts of AHA and AIDA in SSc. Methods: The study included consecutive SSc patients (n = 116, aged 53 ± 13 years, 83.6% females, median disease duration 7 years) with clinically suspected heart involvement (symptoms, abnormal ECG, abnormal troponin I or natriuretic peptides, and abnormal echocardiography). All SSc patients underwent CMR. Serum AHA and AIDA were measured by indirect immunofluorescence in SSc and in control groups of non-inflammatory cardiac disease (NICD) (n = 160), ischemic heart failure (IHF) (n = 141), and normal blood donors (NBD) (n = 270). AHA and AIDA status in SSc was correlated with baseline clinical, diagnostic features, and outcome. Results: The frequency of AHA was higher in SSc (57/116, 49%, p < 0.00001) than in NICD (2/160, 1%), IHF (2/141, 1%), or NBD (7/270, 2.5%). The frequency of AIDA was higher (65/116, 56%, p < 0.00001) in SSc than in NICD (6/160, 3.75%), IHF (3/141, 2%), or NBD (1/270, 0.37%). AHAs were associated with interstitial lung disease (p = 0.04), history of chest pain (p = 0.026), abnormal troponin (p = 0.006), AIDA (p = 0.000), and current immunosuppression (p = 0.01). AHAs were associated with death (p = 0.02) and overall cardiac events during follow-up (p = 0.017). Conclusions: The high frequencies of AHA and AIDA suggest a high burden of underdiagnosed autoimmune HInv in SSc. In keeping with the negative prognostic impact of HInv in SSc, AHAs were associated with dismal prognosis. Full article
(This article belongs to the Special Issue Advances in Identification and Management of Systemic Sclerosis)
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<p>Representative Anti-Heart Auto-antibodies (AHA) and Anti-Intercalated Disk Autoantibodies (AIDA) patterns by indirect immunofluorescence test. Negative AHA, AIDA, and ANA control serum pattern on human heart tissue (panel (<b>a</b>), ×200) and on human skeletal muscle (panel (<b>b</b>), ×400). <span class="html-italic">Organ-specific AHA pattern</span>: panel (<b>A</b>) on human heart tissue: strong diffuse cytoplasmic staining of cardiac myocytes (organ-specific AHA pattern) (×400); panel (<b>B</b>) (×400) on human skeletal muscle tissue: negative. <span class="html-italic">Organ-specific AHA and AIDA pattern</span>: panel (<b>C</b>) strong linear staining of the intercalated disks (AIDA pattern) (white arrows) and associated organ-specific AHA diffuse and fine striational pattern (×400); panel (<b>D</b>) (×400) on human skeletal muscle tissue: negative. <span class="html-italic">Organ-specific AHA and ANA pattern</span>: panel (<b>E</b>) on human heart tissue: strong diffuse cytoplasmic staining of cardiac myocytes (organ-specific AHA pattern) and associated antinuclear antibody (ANA) (white arrows) (×200); panel (<b>F</b>) (×200) on human skeletal muscle tissue: negative for AHA and positive for ANA (white arrows). Note the intracellular location of ANA on human heart and the peripheral location of ANA on skeletal muscle.</p>
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<p>Survival curves according to auto-antibodies status. (<b>A</b>) Kaplan–Meier survival curves in systemic sclerosis (SSc) patients according to Anti-Heart Autoantibodies (AHA) status. AHA positive SSc patients have lower survival (<span class="html-italic">p</span> = 0.005). (<b>B</b>) Kaplan–Meier curves comparing survival in systemic sclerosis (SSc) patients as a function of Anti-Centromere Autoantibody (ACA); ACA positive SSc patients have better survival (<span class="html-italic">p</span> = 0.036). (<b>C</b>) Anti-Nuclear Autoantibody (ANA) status. ANA positive SSc patients have better survival (<span class="html-italic">p</span> = 0.002). Kaplan–Meier curves in systemic sclerosis (SSc) comparing time to cardiac worsening as a function of (<b>D</b>) Anti-Heart Autoantibodies (AHA), AHA positive SSc patients have lower survival free from cardiac worsening (<span class="html-italic">p</span> = 0.017); (<b>E</b>) Anti-Centromere Autoantibody (ACA), ACA positive SSc patients have higher survival free from cardiac worsening (<span class="html-italic">p</span> = 0.016); (<b>F</b>) Anti-Nuclear Autoantibody (ANA) status. ANA positive SSc patients have higher survival free from cardiac worsening (<span class="html-italic">p</span> = 0.010). In all curves, 0 = negative antibody status, 1 = positive antibody status.</p>
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13 pages, 844 KiB  
Review
Chronic Kidney Disease and Heart Failure–Everyday Diagnostic Challenges
by Anna Adamska-Wełnicka, Marcin Wełnicki, Artur Mamcarz and Ryszard Gellert
Diagnostics 2021, 11(11), 2164; https://doi.org/10.3390/diagnostics11112164 - 22 Nov 2021
Cited by 7 | Viewed by 3750
Abstract
Is advanced chronic kidney disease (CKD) a cardiac “no man’s land”? Chronic heart failure (HF) is widely believed to be one of the most serious medical challenges of the 21st century. Moreover, the number of patients with CKD is increasing. To date, patients [...] Read more.
Is advanced chronic kidney disease (CKD) a cardiac “no man’s land”? Chronic heart failure (HF) is widely believed to be one of the most serious medical challenges of the 21st century. Moreover, the number of patients with CKD is increasing. To date, patients with estimated glomerular filtration rates <30 mL/min/1.73 m2 have frequently been excluded from large, randomized clinical trials. Although this situation is slowly changing, in everyday practice we continue to struggle with problems that are not clearly addressed in the guidelines. This literature review was conducted by an interdisciplinary group, which comprised a nephrologist, internal medicine specialists, and cardiologist. In this review, we discuss the difficulties in ruling out HF for patients with advanced CKD and issues regarding the cardiotoxicity of dialysis fistulas and the occurrence of pulmonary hypertension in patients with CKD. Due to the recent publication of the new HF guidelines by the European Society of Cardiology, this is a good time to address these difficult issues. Contrary to appearances, these are not niche issues, but problems that affect many patients. Full article
(This article belongs to the Special Issue Diagnosis and Management of Heart Failure)
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<p>Basic mechanisms underlying the mutual dependencies of heart and kidney functions. CO, cardiac output; RAAS, renin-angiotensin-aldosterone system. A figure prepared by the authors on the basis of pathophysiological issues described by Rangaswami et al. [<a href="#B8-diagnostics-11-02164" class="html-bibr">8</a>]. The figure shows the influence of heart and kidney function on the afterload and preload values. The decrease in cardiac output due to heart failure causes renal hypoperfusion. The sympathetic nervous system, the renin-angiotensin-aldosterone system and the release of vasopressin are activated in order to increase systemic vascular resistance and circulating blood volume. Increased venous pressure causes renal congestion, which additionally impairs their function. A decrease in glomerular filtration causes not only hypervolemia (increased preload), but also unfavorable changes in ion concentrations, which affects the contractility of cardiomyocytes. In addition, along with the deteriorating kidney function, disturbances in calcium-phosphate metabolism increase and the synthesis of erythropoietin is impaired, which also adversely affects the function of blood vessels and the heart muscle.</p>
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<p>Difficulties in implementing the current diagnostic algorithm for HF for patients with CKD [<a href="#B1-diagnostics-11-02164" class="html-bibr">1</a>,<a href="#B10-diagnostics-11-02164" class="html-bibr">10</a>,<a href="#B11-diagnostics-11-02164" class="html-bibr">11</a>,<a href="#B12-diagnostics-11-02164" class="html-bibr">12</a>,<a href="#B13-diagnostics-11-02164" class="html-bibr">13</a>,<a href="#B14-diagnostics-11-02164" class="html-bibr">14</a>,<a href="#B15-diagnostics-11-02164" class="html-bibr">15</a>,<a href="#B16-diagnostics-11-02164" class="html-bibr">16</a>,<a href="#B17-diagnostics-11-02164" class="html-bibr">17</a>]. The HF diagnostic algorithm (left) includes symptoms that are common in patients with CKD, with or without HF (center). Ruling out HF in patients with CKD may require further differentiation; (right) some potential differentiation factors are proposed; For example, arterial hypertension and diabetes are the primary risk factors for both CKD and HF. In a patient with a significantly reduced eGFR, dyspnea and oedema may be caused by both CKD and concomitant or occurring de novo HF. With the deteriorating renal function, the unequivocal interpretation of the elevated concentration of natriuretic peptides becomes troublesome and electrolyte disturbances may affect the ECG. In such a setting, it is difficult to conclude whether HF coexists with CKD or whether the deterioration of cardiac function is secondary to renal failure and therefore potentially reversible. This issue is discussed in detail later in the article; HF: heart failure; CKD: chronic kidney disease; ECG: electrocardiogram; BNP: brain natriuretic peptide; LV: left ventricular; eGFR: estimated glomerular filtration rate.</p>
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12 pages, 4554 KiB  
Article
A Novel Algorithm Using Cell Population Data (VCS Parameters) as a Screening Discriminant between Alpha and Beta Thalassemia Traits
by Angeli Ambayya, Santina Sahibon, Thoo Wei Yang, Qian-Yun Zhang, Rosline Hassan and Jameela Sathar
Diagnostics 2021, 11(11), 2163; https://doi.org/10.3390/diagnostics11112163 - 22 Nov 2021
Cited by 4 | Viewed by 2410
Abstract
Thalassemia is one of the major inherited haematological disorders in the Southeast Asia region. This study explored the potential utility of red blood cell (RBC) parameters and reticulocyte cell population data (CPD) parameters in the differential diagnosis of α and β-thalassaemia traits as [...] Read more.
Thalassemia is one of the major inherited haematological disorders in the Southeast Asia region. This study explored the potential utility of red blood cell (RBC) parameters and reticulocyte cell population data (CPD) parameters in the differential diagnosis of α and β-thalassaemia traits as a rapid and cost-effective tool for screening of thalassemia traits. In this study, a total of 1597 subjects (1394 apparently healthy subjects, 155 subjects with α-thalassaemia trait, and 48 subjects with β-thalassaemia trait) were accrued. The parameters studied were the RBC parameters and reticulocyte CPD parameters derived from Unicel DxH800. A novel algorithm named αβ-algorithm was developed: (MN-LMALS-RET × RDW) − MCH) to discriminate α from β-thalassaemia trait with a cut-off value of 1742.5 [AUC = 0.966, sensitivity = 92%, specificity = 90%, 95% CI = 0.94–0.99]. Two prospective studies were carried: an in-house cohort to assess the specificity of this algorithm in 310 samples comprising various RBC disorders and in an interlaboratory cohort of 65 α-thalassemia trait, and 30 β-thalassaemia trait subjects to assess the reproducibility of the findings. We propose the αβ-algorithm to serve as a rapid, inexpensive surrogate evaluation tool of α and β-thalassaemia in the population screening of thalassemia traits in geographic regions with a high burden of these inherited blood disorders. Full article
(This article belongs to the Special Issue Advances in Hematology Laboratory)
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<p>(<b>a</b>,<b>b</b>) ROC curves of RBC parameters and reticulocyte CPD to distinguish α from β thalassaemia trait.</p>
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<p>The ROC curve for discriminating α from β-thalassaemia traits generated from the αβ-algorithm.</p>
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<p>(<b>a</b>–<b>d</b>) Box and whisker plot for MCH, RDW, MN-LMALS-RET (labelled as @MNLMALSRET in <a href="#diagnostics-11-02163-f003" class="html-fig">Figure 3</a>c and the αβ-algorithm between the α and β-thalassaemia trait and the control group (apparently healthy subjects). * refers to the outliers.</p>
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<p>Flowchart representing the αβ-algorithm incorporated into the screening algorithm for voluntary and cascade screening in Malaysia’s Clinical Practice Guideline for Management of Transfusion Dependent Thalassaemia [<a href="#B4-diagnostics-11-02163" class="html-bibr">4</a>].</p>
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<p>Box and whisker plot for the αβ-algorithm in various red cell disorders (IDA, HbE trait (labelled as HBE in this figure), iron deficiency, α thalassaemia trait (labelled as alpha thalassemia), and β-thalassaemia trait (labelled as beta-thalassemia). Outliers are marked as “*” and “⁰” in the HbE trait and β-thalassaemia trait groups.</p>
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17 pages, 21600 KiB  
Article
Radiologic Differentiation between Granulomatosis with Polyangiitis and Its Mimics Involving the Skull Base in Humans Using High-Resolution Magnetic Resonance Imaging
by Boeun Lee, Yun Jung Bae, Byung Se Choi, Byung Yoon Choi, Se Jin Cho, Hyojin Kim and Jae Hyoung Kim
Diagnostics 2021, 11(11), 2162; https://doi.org/10.3390/diagnostics11112162 - 22 Nov 2021
Cited by 4 | Viewed by 3077
Abstract
Granulomatosis with polyangiitis (GPA) can involve the skull base or the Eustachian tubes. GPA is diagnosed on the basis of clinical manifestations and serological tests, although it is challenging to discriminate GPA from infectious processes driving skull base osteomyelitis (SBO) and malignant processes [...] Read more.
Granulomatosis with polyangiitis (GPA) can involve the skull base or the Eustachian tubes. GPA is diagnosed on the basis of clinical manifestations and serological tests, although it is challenging to discriminate GPA from infectious processes driving skull base osteomyelitis (SBO) and malignant processes such as nasopharyngeal carcinoma (NPC). Moreover, current serological tests have a low sensitivity and cannot distinguish GPA from these other conditions. We hypothesized that certain MRI characteristics would differ significantly among conditions and aimed to evaluate whether the features could differentiate between GPA, SBO, and NPC involving the skull base. We retrospectively evaluated the MRI findings of patients with GPA, SBO, and NPC. We performed univariable logistic regression analyses to identify the predictive variables for differentiating between conditions and evaluated their diagnostic values. We showed, for the first time, that certain MRI findings significantly differed between patients with GPA and those with SBO or NPC, including the lesion morphology and extent, the apparent diffusion coefficient (ADC) values, the contrast enhancement patterns, the presence or absence of necrosis, and retropharyngeal lymphadenopathy. In conclusion, utilizing certain MRI features can improve the diagnostic performance of MRI by differentiating GPA with skull base involvement from other conditions with similar radiologic findings, including SBO and NPC, facilitating treatment plans and, thus, improving patient outcomes. Full article
(This article belongs to the Special Issue Head and Neck Imaging)
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<p>Comparison of ADC values between GPA lesion (<b>a</b>,<b>b</b>), and SBO lesion (<b>c</b>,<b>d</b>). (<b>a</b>) Axial contrast-enhanced T1WI of a 77-year-old male diagnosed with GPA shows infiltrative enhancing lesion (arrow) involving the right-side nasopharynx, parapharyngeal space, prevertebral muscle, and skull base. (<b>b</b>) His ADC map shows a relatively low ADC value inside the enhancing lesion (arrow). The measured value was 0.71 × 10<sup>−3</sup> mm<sup>2</sup>/s. (<b>c</b>) On axial contrast-enhanced T1WI, a 79-year-old male diagnosed with SBO shows large area of infiltrative enhancing lesion (arrow) involving the nasopharynx, parapharyngeal space, carotid space, prevertebral and retropharyngeal space, skull base, and adjacent infratemporal fossa. (<b>d</b>) On his ADC map, the lesion shows relatively high ADC values inside the enhancing lesion (arrow), which was measured as 1.56 × 10<sup>−3</sup> mm<sup>2</sup>/s.</p>
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<p>Dural involvement in a 54-year-old female patient diagnosed with GPA. (<b>a</b>) Axial, and (<b>b</b>) coronal contrast-enhanced T1WI show enhancing dural thickening at right temporal convexity and right tentorium (arrows).</p>
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<p>Retropharyngeal lymphadenopathy in a 50-year-old male patient diagnosed with NPC. (<b>a</b>) Axial contrast-enhanced T1WI shows enhancing mass-forming lesion in the left posterolateral nasopharynx (arrow). (<b>b</b>) In this patient, bilateral retropharyngeal lymph nodes are enlarged (arrows), suggesting retropharyngeal nodal metastases.</p>
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<p>Comparison between GPA and SBO. (<b>a</b>) On axial contrast-enhanced T1WI of a 45-year-old female, GPA lesion shows relatively homogeneously enhancing infiltrative lesion (arrows) centered in the left side parapharyngeal space, skewed laterally from the nasopharynx. (<b>b</b>) SBO lesion of a 60-year-old male shows heterogeneously enhancing infiltrative lesion involving bilateral nasopharynx, prevertebral space, and skull base. Notably, focal internal necrosis (arrow) is seen in the right skull base area.</p>
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<p>Comparison between GPA and NPC. (<b>a</b>) Axial contrast-enhanced T1WI of a 54-year-old female shows GPA lesion centered in the right parapharyngeal space, skewed laterally from the nasopharynx (arrow). Its infiltrative enhancement causes a poorly defined margin. (<b>b</b>) On the contrary, NPC lesion in a 46-year-old female shows enhancing lesion in the right lateral and posterior nasopharynx (arrow). Although it extends into adjacent parapharyngeal space, the lesion is centered in the nasopharyngeal wall. In addition, the margin of NPC is relatively well-defined compared to that of GPA lesion.</p>
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12 pages, 3100 KiB  
Article
The Clinical Significance of the Hyperintense Acute Reperfusion Marker Sign in Subacute Infarction Patients
by Ji Young Lee, Kyung Mi Lee, Hyug-Gi Kim, Ho-Geol Woo, Jin San Lee and Eui Jong Kim
Diagnostics 2021, 11(11), 2161; https://doi.org/10.3390/diagnostics11112161 - 22 Nov 2021
Viewed by 3232
Abstract
Purpose: The hyperintense acute reperfusion marker (HARM) is characterized by the delayed enhancement of the subarachnoid or subpial space observed on postcontrast fluid-attenuated inversion recovery (FLAIR) images, and is considered a cerebral reperfusion marker for various brain disorders, including infarction. In this study, [...] Read more.
Purpose: The hyperintense acute reperfusion marker (HARM) is characterized by the delayed enhancement of the subarachnoid or subpial space observed on postcontrast fluid-attenuated inversion recovery (FLAIR) images, and is considered a cerebral reperfusion marker for various brain disorders, including infarction. In this study, we evaluated the cerebral distribution patterns of HARM for discriminating between an enhancing subacute infarction and an enhancing mass located in the cortex and subcortical white matter. Materials and methods: We analyzed consecutive patients who experienced a subacute ischemic stroke, were hospitalized, and underwent conventional brain magnetic resonance imaging including postcontrast FLAIR within 14 days from symptom onset, as well as those who had lesions corresponding to a clinical sign detected by diffusion-weighted imaging and postcontrast T1-weighted imaging between May 2019 and May 2021. A total of 199 patients were included in the study. Of them, 94 were finally included in the subacute infarction group. During the same period, 76 enhancing masses located in the cortex or subcortical white matter, which were subcategorized as metastasis, malignant glioma, and lymphoma, were analyzed. We analyzed the overall incidence of HARM in subacute ischemic stroke cases, and compared the enhancement patterns between cortical infarctions and cortical masses. Results: Among 94 patients with subacute stroke, 78 patients (83%) presented HARM, and among 76 patients with subcortical masses, 48 patients (63%) presented peripheral rim enhancement. Of 170 subcortical enhancing lesions, 88 (51.8%) showed HARM, and 78 (88.6%) were determined to be subacute infarction. Among 94 patients with subacute stroke, 48 patients (51%) had diffusion restrictions, and HARM was found in 39 patients (81.2%). Of the 46 patients (49%) without diffusion restriction, 39 patients (84.8%) showed HARM. Conclusions: The presence of HARM was significantly associated with subacute infarctions. For the masses, a peripheral rim enhancement pattern was observed around the mass rather than the cerebral sulci on postcontrast FLAIR. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>Typical HARM related to subacute infarction. A 65-year-old male presented with back pain and left side weakness after slipping in his house. DWI (<b>A</b>) with low signal intensity on the ADC map (not shown) showing a barely discernible hyperintense sign. Postcontrast T1WI (<b>C</b>) showing multiple nodular enhancement at the right parietal cortex (red arrow). A postcontrast FLAIR image (<b>D</b>) showing a linear enhancement along the adjacent right parietal sulci (yellow arrow), which is well-visualized as compared with the non-enhanced FLAIR (<b>B</b>) consistent with the HARM. Carotid TOF-MRA showing occlusion of the right proximal ICA (blue arrow, (<b>E</b>)).</p>
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<p>HARM related to subacute infarction. A 67-year-old male presented with a transient language problem and right arm weakness with preceding thunderclap headache, approximated 10 days. Initial DWI (<b>A</b>) showing no diffusion restriction lesion in the brain. Postcontrast T1WI (<b>C</b>) showing two nodular enhancements at the left frontal cortex (red arrow). Postcontrast FLAIR image (<b>D</b>) showing the typical HARM (yellow arrow), which is well-visualized compared with the non-enhanced FLAIR (<b>B</b>).</p>
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<p>HARM related to a cortical enhancing lesion. A 76-year-old female presented with gait disturbance for 2 weeks. (<b>A</b>–<b>D</b>) Postcontrast T1WI showing nodular enhancement at the left anterior frontal cortex (red arrow). A postcontrast FLAIR image showing enhancement at the left frontal cortex and another linear, and stronger, enhancement along the left frontal sulci and left occipital sulci (yellow arrow, (<b>E</b>–<b>H</b>)). Based on the HARM, this patient was treated with an antiplatelet and aspirin for 3 months, and her symptoms improved.</p>
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<p>Rim enhancement superficial to the metastatic brain tumors. A 55-year-old female presented with headache showed focal homogeneously enhancing mass at right precentral gyrus, unknown cause (red arrow, (<b>A</b>)). Peripheral rim enhancement around the mass is observed on postcontrast FLAIR (yellow arrow, (<b>B</b>)), which means the cortical lesion is a mass rather than an infarction. The patient was diagnosed with lung cancer through further examination, including bronchoscopic lung biopsy, and we concluded that the enhancing lesions were metastasis from lung cancer. Subsequently, she received whole brain radiotherapy, and was started on treatment with combination chemotherapy. Follow up MRI after 3 months shows complete tumor disappearance (<b>C</b>).</p>
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10 pages, 1280 KiB  
Article
A Nomogram for Predicting Laparoscopic and Endoscopic Cooperative Surgery during the Endoscopic Resection of Subepithelial Tumors of the Upper Gastrointestinal Tract
by Shun-Wen Hsiao, Mei-Wen Chen, Chia-Wei Yang, Kuo-Hua Lin, Yang-Yuan Chen, Chew-Teng Kor, Siou-Ping Huang and Hsu-Heng Yen
Diagnostics 2021, 11(11), 2160; https://doi.org/10.3390/diagnostics11112160 - 22 Nov 2021
Cited by 6 | Viewed by 2234
Abstract
Background: Considering the widespread use of esophagogastroduodenoscopy, the prevalence of upper gastrointestinal (GI) subepithelial tumors (SET) increases. For relatively safer removal of upper GI SETs, endoscopic submucosal dissection (ESD) has been developed as an alternative to surgery. This study aimed to analyze the [...] Read more.
Background: Considering the widespread use of esophagogastroduodenoscopy, the prevalence of upper gastrointestinal (GI) subepithelial tumors (SET) increases. For relatively safer removal of upper GI SETs, endoscopic submucosal dissection (ESD) has been developed as an alternative to surgery. This study aimed to analyze the outcome of endoscopic resection for SETs and develop a prediction model for the need for laparoscopic and endoscopic cooperative surgery (LECS) during the procedure. Method: We retrospectively analyzed 123 patients who underwent endoscopic resection for upper GI SETs between January 2012 and December 2020 at our institution. Intraoperatively, they underwent ESD or submucosal tunneling endoscopic resection (STER). Results: ESD and STER were performed in 107 and 16 patients, respectively. The median age was 55 years, and the average tumor size was 1.5 cm. En bloc resection was achieved in 114 patients (92.7%). The median follow-up duration was 242 days without recurrence. Perforation occurred in 47 patients (38.2%), and 30 patients (24.4%) underwent LECS. Most perforations occurred in the fundus. Through multivariable analysis, we built a nomogram that can predict LECS requirement according to tumor location, size, patient age, and sex. The prediction model exhibited good discrimination ability, with an area under the curve (AUC) of 0.893. Conclusions: Endoscopic resection is a noninvasive procedure for small upper-GI SETs. Most perforations can be successfully managed endoscopically. The prediction model for LECS requirement is useful in treatment planning. Full article
(This article belongs to the Special Issue Diagnostic Imaging of Gastrointestinal Diseases)
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<p>Nomogram of the prediction model.</p>
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<p>ROC analysis for predicting LECS requirement during endoscopic resection.</p>
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<p>Calibration plot for predicting LECS requirement during endoscopic resection.</p>
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10 pages, 921 KiB  
Article
Low Lymphocyte-to-Monocyte Ratio Is the Potential Indicator of Worse Overall Survival in Patients with Renal Cell Carcinoma and Venous Tumor Thrombus
by Łukasz Zapała, Michał Kunc, Sumit Sharma, Wojciech Biernat and Piotr Radziszewski
Diagnostics 2021, 11(11), 2159; https://doi.org/10.3390/diagnostics11112159 - 21 Nov 2021
Cited by 10 | Viewed by 2021
Abstract
The purpose of the study was to determine the influence of lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) values on the prognosis in patients with renal cell carcinoma (RCC) and venous tumor thrombus. The respective data of 91 patients treated [...] Read more.
The purpose of the study was to determine the influence of lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) values on the prognosis in patients with renal cell carcinoma (RCC) and venous tumor thrombus. The respective data of 91 patients treated with radical surgery in the years 2012–2021 in 2 tertiary referral urological centers were retrieved from local medical databases. Mean calculated 3-year overall survival (OS) reached 70% (mean follow-up 35.3 months). The association between lower LMR and the presence of tumor necrosis (p = 0.0004) was observed. Amongst systemic inflammatory markers, only LMR was selected as the sensitive marker predicting death with a calculated cut-off value of 2.53. OS was decreased in patients presenting with low LMR when compared to the high LMR group (39% vs. 82%, p = 0.0011). Neither NLR nor PLR were associated with survival rates. In multivariate analysis, LMR was identified as the independent prognostic factor (HR = 0.20, 95% CI 0.07–0.55, p = 0.001). Low values of LMR (<2.53) are independently connected with poorer OS in patients with RCC and coexisting tumor thrombus. The incorporation of the hematological variables into the prognostic model greatly increased its accuracy in predicting survival in the distinctive subpopulation of patients with RCC. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Associations between LMR and tumor necrosis. The presence of necrosis was associated with significantly lower LMR (<span class="html-italic">p</span> = 0.0004, Mann-Whitney U test). Horizontal lines inside boxes show median values. The lower and upper hinges correspond to the first and third quartiles (the 25th and 75th percentiles). Upper and lower whiskers indicate 1.5 interquartile range of the lower and upper quartile, respectively. Circles represent individual measures. Abbreviations: LMR: lymphocyte-to-monocyte ratio; PLR: platelet-to-lymphocyte.</p>
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<p>Receiver operating curves for NLR, LMR, PLR, versus event (death). Q values were calculated with Benjamini-Hochberg correction. *—statistically significant. Abbreviations: NLR: neutrophil-to-lymphocyte ratio; LMR: lymphocyte-to-monocyte ratio; PLR: platelet-to-lymphocyte.</p>
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<p>Kaplan-Meier curves with confidence intervals for overall survival stratified by LMR values. <span class="html-italic">p</span>-value was calculated with log-rank test. Abbreviations: LMR: lymphocyte-to-monocyte ratio. Low LMR: below cut-off.</p>
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10 pages, 1017 KiB  
Article
Sarcopenia Diagnosis: Reliability of the Ultrasound Assessment of the Tibialis Anterior Muscle as an Alternative Evaluation Tool
by Massimiliano Leigheb, Alessandro de Sire, Matteo Colangelo, Domenico Zagaria, Federico Alberto Grassi, Ottavio Rena, Patrizio Conte, Pierluigi Neri, Alessandro Carriero, Gian Mauro Sacchetti, Fabio Penna, Giuseppina Caretti and Elisabetta Ferraro
Diagnostics 2021, 11(11), 2158; https://doi.org/10.3390/diagnostics11112158 - 21 Nov 2021
Cited by 29 | Viewed by 3726
Abstract
Sarcopenia is a skeletal muscle disorder characterized by reduced muscle mass, strength, and performance. Muscle ultrasound can be helpful in assessing muscle mass, quality, and architecture, and thus possibly useful for diagnosing or screening sarcopenia. The objective of this study was to evaluate [...] Read more.
Sarcopenia is a skeletal muscle disorder characterized by reduced muscle mass, strength, and performance. Muscle ultrasound can be helpful in assessing muscle mass, quality, and architecture, and thus possibly useful for diagnosing or screening sarcopenia. The objective of this study was to evaluate the reliability of ultrasound assessment of tibialis anterior muscle in sarcopenia diagnosis. We included subjects undergoing total or partial hip replacement, comparing measures with a healthy control group. We measured the following parameters: tibialis anterior muscle thickness, echogenicity, architecture, stiffness, skeletal muscle index (SMI), hand grip strength, and sarcopenia related quality of life evaluated through the SarQoL questionnaire. We included 33 participants with a mean age of 54.97 ± 23.91 years. In the study group we found reduced tibialis anterior muscle thickness compared to the healthy control group (19.49 ± 4.92 vs. 28.94 ± 3.63 mm, p < 0.05) with significant correlation with SarQoL values (r = 0.80, p < 0.05), dynamometer hand strength (r = 0.72, p < 0.05) and SMI (r = 0.76, p < 0.05). Moreover, we found reduced stiffness (32.21 ± 12.31 vs. 27.07 ± 8.04 Kpa, p < 0.05). AUC measures of ROC curves were 0.89 predicting reduced muscle strength, and 0.97 predicting reduced SMI for tibialis anterior muscle thickness, while they were 0.73 and 0.85, respectively, for muscle stiffness. Our findings showed that ultrasound assessment of tibialis anterior muscle might be considered a reliable measurement tool to evaluate sarcopenia. Full article
(This article belongs to the Special Issue Advance in the Diagnostics and Management of Musculoskeletal Diseases)
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<p>Tibialis anterior muscle ultrasound assessment in terms of echogenicity, grade 1 (<b>A</b>), grade 2 (<b>B</b>), and grade 3 (<b>C</b>), and stiffness, measured with shear wave elastography with grade 1 (<b>D</b>), grade 2 (<b>E</b>), and grade 3 (<b>F</b>).</p>
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<p>ROC curves of tibialis anterior muscle thickness with SMI (<b>a</b>) and HGS (<b>b</b>); ROC curves of tibialis anterior muscle stiffness with SMI (<b>c</b>) and HGS (<b>d</b>).</p>
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10 pages, 438 KiB  
Article
Immunoreactivity of Polish Lyme Disease Patient Sera to Specific Borrelia Antigens—Part 1
by Iwona Wojciechowska-Koszko, Magdalena Mnichowska-Polanowska, Paweł Kwiatkowski, Paulina Roszkowska, Monika Sienkiewicz and Barbara Dołęgowska
Diagnostics 2021, 11(11), 2157; https://doi.org/10.3390/diagnostics11112157 - 21 Nov 2021
Cited by 6 | Viewed by 2908
Abstract
The diverse clinical picture and the non-specificity of symptoms in Lyme disease (LD) require the implementation of effective diagnostics, which should take into account the heterogeneity of Borrelia antigens. According to available guidelines, laboratories should use a two-tier serological diagnosis based on the [...] Read more.
The diverse clinical picture and the non-specificity of symptoms in Lyme disease (LD) require the implementation of effective diagnostics, which should take into account the heterogeneity of Borrelia antigens. According to available guidelines, laboratories should use a two-tier serological diagnosis based on the enzyme-linked immunosorbent (ELISA) screening test and confirmation of the immunoblot (IB). The aim of the study was to investigate the immunoreactivity of LD patient sera to Borrelia antigens and to attempt to identify the genospecies responsible for LD using an ELISA–IB assay combination. Eighty patients with suspected LD and 22 healthy people participated in the study. All samples were tested with ELISA and IB assays in both IgM and IgG antibodies. In the case of the ELISA assay, more positive results were obtained in the IgM class than in the IgG class. In the case of the IB assay, positive results dominated in the IgG class. Positive results obtained in the IB assay most often showed IgM antibodies against the OspC and flagellin antigens, whereas the IgG antibodies were against VlsE, BmpA, OspC, p41, and p83 antigens. The IB assay is an important part of LD serodiagnosis and should be mandatory in diagnostic laboratories. Full article
(This article belongs to the Special Issue Lyme Disease: Companion Diagnostics and Precision Medicine)
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<p>The number of positive results obtained from Lyme disease patients (experimental group) and healthy individuals (control group) for the IgM (<b>a</b>) and IgG (<b>b</b>) antibody types for particular antigens, included in the immunoblot assay. The white-colored mark is the number of antigens obtained from positive results; the grey-colored mark is the number of antigens obtained from negative results.</p>
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12 pages, 777 KiB  
Article
Applicability of Anatomic and Physiologic Scoring Systems for the Prediction of Outcome in Polytraumatized Patients with Blunt Aortic Injuries
by Alexander Omar, Marcel Winkelmann, Emmanouil Liodakis, Jan-Dierk Clausen, Tilman Graulich, Mohamed Omar, Christian Krettek and Christian Macke
Diagnostics 2021, 11(11), 2156; https://doi.org/10.3390/diagnostics11112156 - 21 Nov 2021
Cited by 2 | Viewed by 1526
Abstract
Background: Most patients with blunt aortic injuries, who arrive alive in a clinic, suffer from traumatic pseudoaneurysms. Due to modern treatments, the perioperative mortality has significantly decreased. Therefore, it is unclear how exact the prediction of commonly used scoring systems of the outcome [...] Read more.
Background: Most patients with blunt aortic injuries, who arrive alive in a clinic, suffer from traumatic pseudoaneurysms. Due to modern treatments, the perioperative mortality has significantly decreased. Therefore, it is unclear how exact the prediction of commonly used scoring systems of the outcome is. Methods: We analyzed data on 65 polytraumatized patients with blunt aortic injuries. The following scores were calculated: injury severity score (ISS), new injury severity score (NISS), trauma and injury severity score (TRISS), revised trauma score coded (RTSc) and acute physiology and chronic health evaluation II (APACHE II). Subsequently, their predictive value was evaluated using Spearman´s and Kendall´s correlation analysis, logistic regression and receiver operating characteristics (ROC) curves. Results: A proportion of 83% of the patients suffered from a thoracic aortic rupture or rupture with concomitant aortic wall dissection (54/65). The overall mortality was 24.6% (16/65). The sensitivity and specificity were calculated as the area under the receiver operating curves (AUC): NISS 0.812, ISS 0.791, APACHE II 0.884, RTSc 0.679 and TRISS 0.761. Logistic regression showed a slightly higher specificity to anatomical scoring systems (ISS 0.959, NISS 0.980, TRISS 0.957, APACHE II 0.938). The sensitivity was highest in the APACHE II with 0.545. Sensitivity and specificity for the RTSc were not significant. Conclusion: The predictive abilities of all scoring systems were very limited. All scoring systems, except the RTSc, had a high specificity but a low sensitivity. In our study population, the RTSc was not applicable. The APACHE II was the most sensitive score for mortality. Anatomical scoring systems showed a positive correlation with the amount of transfused blood products. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Recruitment flow diagram. We found 70 patients within our hospital databank. Four had to be excluded due to miss-coding and one excluded due to incomplete data.</p>
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<p>ROC curves for the (<b>a</b>) APACHE II, (<b>b</b>) NISS, (<b>c</b>) ISS, (<b>d</b>) ISS without aortic injuries, (<b>e</b>) RTSc and (<b>f</b>) TRISS. APACHE II—acute physiology and chronic health evaluation II; NISS—new injury severity score; ISS—injury severity score; RTSc—revised trauma score coded; TRISS—trauma and injury severity score.</p>
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<p>ROC curves for the (<b>a</b>) APACHE II, (<b>b</b>) NISS, (<b>c</b>) ISS, (<b>d</b>) ISS without aortic injuries, (<b>e</b>) RTSc and (<b>f</b>) TRISS. APACHE II—acute physiology and chronic health evaluation II; NISS—new injury severity score; ISS—injury severity score; RTSc—revised trauma score coded; TRISS—trauma and injury severity score.</p>
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21 pages, 5411 KiB  
Article
Controlling Droplet Marangoni Flows to Improve Microscopy-Based TB Diagnosis
by Stephanie I. Pearlman, Eric M. Tang, Yuankai K. Tao and Frederick R. Haselton
Diagnostics 2021, 11(11), 2155; https://doi.org/10.3390/diagnostics11112155 - 21 Nov 2021
Cited by 5 | Viewed by 3928
Abstract
In developing countries, the most common diagnostic method for tuberculosis (TB) is microscopic examination sputum smears. Current assessment requires time-intensive inspection across the microscope slide area, and this contributes to its poor diagnostic sensitivity of ≈50%. Spatially concentrating TB bacteria in a smaller [...] Read more.
In developing countries, the most common diagnostic method for tuberculosis (TB) is microscopic examination sputum smears. Current assessment requires time-intensive inspection across the microscope slide area, and this contributes to its poor diagnostic sensitivity of ≈50%. Spatially concentrating TB bacteria in a smaller area is one potential approach to improve visual detection and potentially increase sensitivity. We hypothesized that a combination of magnetic concentration and induced droplet Marangoni flow would spatially concentrate Mycobacterium tuberculosis on the slide surface by preferential deposition of beads and TB–bead complexes in the center of an evaporating droplet. To this end, slide substrate and droplet solvent thermal conductivities and solvent surface tension, variables known to impact microfluidic flow patterns in evaporating droplets, were varied to select the most appropriate slide surface coating. Optimization in a model system used goniometry, optical coherence tomography, and microscope images of the final deposition pattern to observe the droplet flows and maximize central deposition of 1 μm fluorescent polystyrene particles and 200 nm nanoparticles (NPs) in 2 μL droplets. Rain-X® polysiloxane glass coating was identified as the best substrate material, with a PBS-Tween droplet solvent. The use of smaller, 200 nm magnetic NPs instead of larger 1 μm beads allowed for bright field imaging of bacteria. Using these optimized components, we compared standard smear methods to the Marangoni-based spatial concentration system, which was paired with magnetic enrichment using iron oxide NPs, isolating M. bovis BCG (BCG) from samples containing 0 and 103 to 106 bacilli/mL. Compared to standard smear preparation, paired analysis demonstrated a combined volumetric and spatial sample enrichment of 100-fold. With further refinement, this magnetic/Marangoni flow concentration approach is expected to improve whole-pathogen microscopy-based diagnosis of TB and other infectious diseases. Full article
(This article belongs to the Special Issue Point-of-Care Diagnostics for Low-Resource Settings)
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<p>Physical phenomena that contribute to Marangoni flow formation and direction. Surface tension (γ) and thermal conductivity (k) of the surface (k<sub>s</sub>) and droplet solvent (k<sub>L</sub>) can be manipulated to create inward- or outward-oriented Marangoni flow patterns in an evaporating droplet. In this case, nonuniform evaporation along the liquid–air interface of the droplet (blue triangle arrows) occurs. This creates a temperature gradient (T) that results in a nonuniform surface tension gradient. When k<sub>s</sub> &lt; 1.45 k<sub>L</sub>, where the temperature at the top of the droplet is warmest, while the contact line is coldest (indicated by red circle), the microfluidic flows within the droplet circulate radially inward along the solid substrate (black triangle arrows) independent of surface tension [<a href="#B10-diagnostics-11-02155" class="html-bibr">10</a>,<a href="#B11-diagnostics-11-02155" class="html-bibr">11</a>] (Adapted from ref. [<a href="#B11-diagnostics-11-02155" class="html-bibr">11</a>]).</p>
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<p>Workflow for combined volumetric and spatial concentration of <span class="html-italic">M.tb</span>. (<b>A</b>) Magnetic nanoparticles are added, incubated with the sample to capture bacilli, and then magnetically separated from the sample. After washing, the bound sample and nanoparticles are recovered in 50 μL PBS-T. (<b>B</b>) The recovered sample is deposited on the Rain-X<sup>®</sup> + poly-L-lysine-coated microscope slide and evaporated at room temperature over a period of time (Δt). (<b>C</b>) The dried sample is stained using the Ziehl–Neelson method, and the central Marangoni deposition area is inspected using microscopy at 1000× magnification. Representative positive samples with increasing <span class="html-italic">M.tb</span> concentrations are shown. (+)—10<sup>4</sup> bacilli/mL; (++) 10<sup>5</sup> bacilli/mL; (+++) 10<sup>6</sup> bacilli/mL. Black scale bar—1 mm; white scale bar—50 μm.</p>
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<p>Deposition of poly-L-lysine onto Rain-X<sup>®</sup>-coated slide. (<b>A</b>) A marked grid was affixed to the back of the microscope slide using tape. (<b>B</b>) Droplets 10 μL in size containing 0.01% poly-L-lysine were spotted onto the microscope slide where indicated. (<b>C</b>) After removing excess poly-L-lysine, 50 μL droplets containing the volumetrically concentrated samples were placed over the poly-L-lysine landing zone and allowed to dry. Location of landing zone in center of droplets indicated by dashed circle. Dyes added to droplets for visualization.</p>
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<p>Contact angle measurements, as shown in insert, of 2 μL MilliQ water droplets on each candidate substrate (mean ± s.d.; n ≥ 13). Coatings with a contact angle less than 85° did not centrally deposit particles during evaporation. Red downward arrow indicates substrate selected for final design (H2O Repel). * Indicates Rain-X<sup>®</sup> product.</p>
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<p>Particle deposition patterns of 2 μL droplets containing green fluorescent polystyrene particles (left of each pair) or 200 nm magnetic nanoparticles (right of each pair) in order of decreasing contact angle. Theory states that Marangoni flows in all droplets are oriented radially inward along the substrate, with the exception of ITO, which is oriented radially outward along the substrate. Because of the strong central deposition pattern, we selected Water Repellent Rain-X<sup>®</sup> (H2O Repel) to covalently coat microscope slides, creating our solid substrate. Scale bar = 500 μm, n = 3. * Indicates Rain-X<sup>®</sup> product.</p>
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<p>Time-lapse images demonstrate formation of Marangoni flow patterns oriented radially inward along the substrate. (<b>A</b>) Starting at 1 min, and every 2 min thereafter until the droplets dried, composite images containing 800 repeated frames in 36 s were taken at the diameter of the 1 μL droplet to image the flow fields produced in the droplet using optical coherence tomography. Flow direction is indicated by red arrows. (<b>B</b>) Top-view microscopy image showing movement of particles inward along the substrate surface of a drop in a 5 μL droplet. A single image was captured using fluorescent imaging with an exposure time of 4 s. White arrows indicate flow direction. Sample contains 10<sup>6</sup> and 10<sup>4</sup> particles/μL. Composite videos for OCT and microscopy series can be found in the <a href="#app1-diagnostics-11-02155" class="html-app">Supplementary Information (Videos S1 and S2)</a>. Red scale bar = 125 μm. White scale bar = 100 μm.</p>
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<p>Effect of volumetric concentration and Marangoni spatial enrichment of 50 μL droplets on smear microscopy (n = 3). BCG-stained pink/red with Ziehl–Neelsen stain. Nanoparticles are brown or may appear as red-orange if extremely concentrated, as seen in the lower right most image. Counterstained objects appear dark blue-purple. The most central deposition area inspected for combined volumetric + Marangoni concentration is indicated by a dashed red circle on the 0 bacilli/mL whole drop image at 40× magnification. In the high magnification columns, 1, 2 (black), and 4 (white) arrows indicate a positive smear. Images selected were representative of the samples inspected. White scale bar = 30 μm. Red scale bar = 300 μm.</p>
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10 pages, 2094 KiB  
Article
Detectability of Head and Neck Cancer via New Computed Tomography Reconstruction Tools including Iterative Reconstruction and Metal Artifact Reduction
by Daniel Troeltzsch, Seyd Shnayien, Max Heiland, Kilian Kreutzer, Jan-Dirk Raguse, Bernd Hamm and Stefan M. Niehues
Diagnostics 2021, 11(11), 2154; https://doi.org/10.3390/diagnostics11112154 - 21 Nov 2021
Cited by 8 | Viewed by 2243
Abstract
State-of-the-art technology in Computed Tomography (CT) includes iterative reconstruction algorithms (IR) and metal artefact reduction (MAR) techniques. The objective of the study is to show the benefits of this technology for the detection of primary and recurrent head and neck cancer. A total [...] Read more.
State-of-the-art technology in Computed Tomography (CT) includes iterative reconstruction algorithms (IR) and metal artefact reduction (MAR) techniques. The objective of the study is to show the benefits of this technology for the detection of primary and recurrent head and neck cancer. A total of 131 patients underwent contrast-enhanced CT for diagnosis of primary and recurrent Head and Neck cancer; 110 patients were included. All scans were reconstructed using iterative reconstruction, and metal artifact reduction was applied when indicated. Tumor detectability was evaluated dichotomously. Histopathological findings were used as a standard of reference. Data were analyzed retrospectively, statistics was performed through diagnostic test characteristics. State-of-the-art Head and Neck CT showed a sensitivity of 0.83 (95% CI; 0.61–0.95) with 0.93 specificity (95% CI; 0.84–0.98) for primary tumor detection. Recurrent tumors were identified with a 0.94 sensitivity (95% CI; 0.71–0.99) and 0.93 specificity (95% CI; 0.84–0.98) in this study. Conclusion: State-of-the-art reconstruction tools improve the diagnostic quality of Head and Neck CT, especially for recurrent tumor detection, compared with data published for standard CT. IR and MAR are easily implemented in routine clinical settings and improve image evaluation by reducing artifacts and image noise while lowering radiation exposure. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>Patient inclusion and exclusion; demographic data; and distribution of Head and Neck Squamous Cell Carcinoma (HNSCC); CT findings.</p>
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<p>Axial CT images with (<b>a</b>) AIDR reconstruction and (<b>b</b>) SEMAR reconstruction illustrating greater homogeneity of the SEMAR dataset and significant reduction of metal artifacts.</p>
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<p>Axial CT images of (<b>a</b>) recurrent HNSCC of tongue edge (highlighted) without SEMAR reconstruction and (<b>b</b>) recurrent HNSCC of tongue edge (highlighted) with SEMAR reconstruction.</p>
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16 pages, 1770 KiB  
Article
Multimer Analysis of Von Willebrand Factor in Von Willebrand Disease with a Hydrasys Semi-Automatic Analyzer—Single-Center Experience
by Ingrid Skornova, Tomas Simurda, Jan Stasko, Jana Zolkova, Juraj Sokol, Pavol Holly, Miroslava Dobrotova, Ivana Plamenova, Jan Hudecek, Monika Brunclikova, Alena Stryckova and Peter Kubisz
Diagnostics 2021, 11(11), 2153; https://doi.org/10.3390/diagnostics11112153 - 20 Nov 2021
Cited by 8 | Viewed by 4667
Abstract
von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder. This disorder develops as a result of defects and/or deficiency of the plasma protein von Willebrand factor (VWF). Laboratory testing for VWF-related disorders requires the assessment of both VWF level and [...] Read more.
von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder. This disorder develops as a result of defects and/or deficiency of the plasma protein von Willebrand factor (VWF). Laboratory testing for VWF-related disorders requires the assessment of both VWF level and VWF activity, the latter requiring multiple assays. As an additional step, an evaluation of VWF structural features by multimer analysis is useful in selective investigations. Multimer analysis is also important for the selection of a suitable VWF therapy preparation (desmopressin, VWF/FVIII concentrate, recombinant VWF) and the determination of the correct dose for the patient. Based on clinical and laboratory findings, including the analysis of VWF multimers, we classified our patients into individual types of VWD. Our study group included 58 patients. The study group consisted of 66% (38 patients) with VWD type 1, 5% (3 patients) with VWD type 2, 7% (4 patients) with VWD type 3, 5% (3 patients) with mixed type 1/2A VWD, and 17% (10 patients) comprising an unclassified group. In this article, we provide an overview of our practical experience using a new complementary method—the analysis of von Willebrand factor multimers with a semi-automatic analyzer Hydrasys 2 scan. We explain the principle, procedure, advantages, and pitfalls associated with the introduction of the VWF multimer analysis methodology into standard VWD diagnostics. Full article
(This article belongs to the Special Issue New Assays in the Diagnosis of Coagulation Protein Disorders)
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<p>Densitometric representation of VWF multimers. (<b>A</b>) Peak intensity directly correlates with VWF multimer concentration. (<b>B</b>) Densitometric representation of peaks from left to right, with peaks 1–3 being LMW, peaks 4–7 being IMW, and all other peaks forming HMW (own data).</p>
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<p>Principle of the determination and visualization of VWF multimers via the semi-automatic method of Hydrasys 2 scanning. Incubation of the first immunofixation of VWF multimers in a gel with a polyclonal anti-VWF-IgG antibody, and incubation of the second immunofixation with peroxidase-conjugated anti-IgG antibody. The gel was subsequently incubated in peroxidase and chromogen substrate (TTF1/TTF2), then dried and prepared for interpretation (own data).</p>
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<p>Analysis of VWF multimers of patients with VWD type 1 (sample number 1 in <a href="#diagnostics-11-02153-t001" class="html-table">Table 1</a>), VWD type 2N (sample number 2 in <a href="#diagnostics-11-02153-t001" class="html-table">Table 1</a>), VWD type 3 (sample number 3 in <a href="#diagnostics-11-02153-t001" class="html-table">Table 1</a>), and VWD U (unclassified) (sample number 4 in <a href="#diagnostics-11-02153-t001" class="html-table">Table 1</a>); (<b>A</b>) semi-automatic Hydrasys 2 scan and (<b>B</b>) densitometric evaluation.</p>
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<p>Algorithm for the diagnosis and classification of von Willebrand disease.</p>
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2 pages, 516 KiB  
Interesting Images
A Rare Case of Duodenal Pseudomelanosis
by Marianna D’Ercole, Gianluca Lopez, Luca Elli, Stefano Ferrero and Giorgio Alberto Croci
Diagnostics 2021, 11(11), 2152; https://doi.org/10.3390/diagnostics11112152 - 20 Nov 2021
Cited by 1 | Viewed by 1955
Abstract
A black-spotted duodenal mucosa was observed during endoscopy of a man with several comorbidities including hypertension and end-stage kidney disease. Histopathological examination revealed pigment-laden macrophages in the lamina propria of the duodenal villi, which was consistent with duodenal pseudomelanosis. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>A 75-year-old man underwent endoscopy for obstructive lithiasic cholangitis. His medical history included gastric resection for non-Hodgkin lymphoma, monoclonal gammopathy of undetermined significance (MGUS), HCV infection, hypertension, and stage 4 chronic kidney disease. His medications included furosemide, metoprolol, and amlodipine. During the endoscopy, the duodenal mucosa presented spotted black pigmentation at the tip of the villi (<b>A</b>). Duodenal biopsy samples stained with routine hematoxylin and eosin (<b>B</b>) showed aggregates of pigment-laden macrophages in the lamina propria of the apical portion of the villi, which tested intensely positive with Perl’s stain for iron; enterocytes demonstrated a faint positivity for Perl’s Prussian blue underneath the microvilli (<b>B</b>, inset). These findings were consistent for duodenal pseudomelanosis, a benign condition which harbors no known clinical sequelae [<a href="#B1-diagnostics-11-02152" class="html-bibr">1</a>,<a href="#B2-diagnostics-11-02152" class="html-bibr">2</a>,<a href="#B3-diagnostics-11-02152" class="html-bibr">3</a>,<a href="#B4-diagnostics-11-02152" class="html-bibr">4</a>,<a href="#B5-diagnostics-11-02152" class="html-bibr">5</a>,<a href="#B6-diagnostics-11-02152" class="html-bibr">6</a>,<a href="#B7-diagnostics-11-02152" class="html-bibr">7</a>,<a href="#B8-diagnostics-11-02152" class="html-bibr">8</a>,<a href="#B9-diagnostics-11-02152" class="html-bibr">9</a>,<a href="#B10-diagnostics-11-02152" class="html-bibr">10</a>,<a href="#B11-diagnostics-11-02152" class="html-bibr">11</a>,<a href="#B12-diagnostics-11-02152" class="html-bibr">12</a>,<a href="#B13-diagnostics-11-02152" class="html-bibr">13</a>].</p>
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Review
Advances of Exosomal miRNAs in Breast Cancer Progression and Diagnosis
by Wenwen Chen, Zhongyu Li, Pengwei Deng, Zhengnan Li, Yuhai Xu, Hongjing Li, Wentao Su and Jianhua Qin
Diagnostics 2021, 11(11), 2151; https://doi.org/10.3390/diagnostics11112151 - 20 Nov 2021
Cited by 17 | Viewed by 3865
Abstract
Breast cancer is one of the most commonly diagnosed malignancies and the leading cause of cancer death in women worldwide. Although many factors associated with breast cancer have been identified, the definite etiology of breast cancer is still unclear. In addition, early diagnosis [...] Read more.
Breast cancer is one of the most commonly diagnosed malignancies and the leading cause of cancer death in women worldwide. Although many factors associated with breast cancer have been identified, the definite etiology of breast cancer is still unclear. In addition, early diagnosis of breast cancer remains challenging. Exosomes are membrane-bound nanovesicles secreted by most types of cells and contain a series of biologically important molecules, such as lipids, proteins, and miRNAs, etc. Emerging evidence shows that exosomes can affect the status of cells by transmitting substances and messages among cells and are involved in various physiological and pathological processes. In breast cancer, exosomes play a significant role in breast tumorigenesis and progression through transfer miRNAs which can be potential biomarkers for early diagnosis of breast cancer. This review discusses the potential utility of exosomal miRNAs in breast cancer progression such as tumorigenesis, metastasis, immune regulation and drug resistance, and further in breast cancer diagnosis. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Breast cancer-related exosomal miRNAs in breast cancer progression.</p>
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<p>Detection approaches for breast cancer-related exosomal miRNA analysis. (<b>A</b>) RT-qPCR method for exosomal miRNA analysis, the length of miRNA was increased by stem-loop (left) or poly (<b>A</b>) tailing (right) method [<a href="#B112-diagnostics-11-02151" class="html-bibr">112</a>]. (<b>B</b>) Flow chart for miRNA sequencing. The length of miRNA was increased by an adapter at both 3′ and 5′ sides. (<b>C</b>) Molecular beacon for single (left) [<a href="#B110-diagnostics-11-02151" class="html-bibr">110</a>] and multiple (right) [<a href="#B113-diagnostics-11-02151" class="html-bibr">113</a>] exosomal miRNA analysis. (<b>D</b>) Schematic representation of the electrochemical platform for exosomal miRNA detection [<a href="#B114-diagnostics-11-02151" class="html-bibr">114</a>].</p>
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11 pages, 2585 KiB  
Article
Exploring Machine Learning Techniques to Predict the Response to Omalizumab in Chronic Spontaneous Urticaria
by Davide Stefano Sardina, Giuseppe Valenti, Francesco Papia and Carina Gabriela Uasuf
Diagnostics 2021, 11(11), 2150; https://doi.org/10.3390/diagnostics11112150 - 20 Nov 2021
Cited by 3 | Viewed by 2396
Abstract
Background: Omalizumab is the best treatment for patients with chronic spontaneous urticaria (CSU). Machine learning (ML) approaches can be used to predict response to therapy and the effectiveness of a treatment. No studies are available on the use of ML techniques to predict [...] Read more.
Background: Omalizumab is the best treatment for patients with chronic spontaneous urticaria (CSU). Machine learning (ML) approaches can be used to predict response to therapy and the effectiveness of a treatment. No studies are available on the use of ML techniques to predict the response to Omalizumab in CSU. Methods: Data from 132 CSU outpatients were analyzed. Urticaria Activity Score over 7 days (UAS7) and treatment efficacy were assessed. Clinical and demographic characteristics were used for training and validating ML models to predict the response to treatment. Two methodologies were used to label the data based on the response to treatment (UAS7 ≥ 6): (A) at 1, 3 and 5 months; (B) classifying the patients as early responders (ER), late responders (LR) or non-responders (NR) (ER: UAS 7 ≥ 6 at first month, LR: UAS 7 ≥ 6 at third month, NR: if none of the previous conditions occurred). Results: ER were predominantly characterized by hypertension, while LR mainly suffered from asthma and hypothyroidism. A slight positive correlation (R2 = 0.21) was found between total IgE levels and UAS7 at 1 month. Variable Importance Analysis (VIA) reported D-dimer and C-reactive proteins as the key blood tests for the performance of learning techniques. Using methodology (A), SVM (specificity of 0.81) and k-NN (sensitivity of 0.8) are the best models to predict LR at the third month. Conclusion: k-NN plus the SVM model could be used to identify the response to treatment. D-dimer and C-reactive proteins have greater predictive power in training ML models. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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<p>Variability of the response to Omalizumab over 5 months treatment.</p>
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<p>UAS7 Flow diagram according to CSU patient groups.</p>
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<p>Response to omalizumab in South Italian CSU patients.</p>
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<p>Variable Importance Analysis for the prediction of the response to omalizumab after 1 month treatment.</p>
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<p>Variable Importance Analysis for the prediction of the response to omalizumab after 3 months treatment.</p>
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<p>Variable Importance Analysis for the prediction of the response to omalizumab after 5 months treatment.</p>
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<p>Feature selection algorithm based on importance.</p>
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13 pages, 1336 KiB  
Review
The Influences of Omega-3 Polyunsaturated Fatty Acids on the Development of Skin Cancers
by Yoko Minokawa, Yu Sawada and Motonobu Nakamura
Diagnostics 2021, 11(11), 2149; https://doi.org/10.3390/diagnostics11112149 - 19 Nov 2021
Cited by 8 | Viewed by 4093
Abstract
Dietary nutrition intake is essential for human beings and influences various physiological and pathological actions in the human body. Among various nutritional factors, dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) has been shown to have various beneficial effects against inflammatory diseases. In [...] Read more.
Dietary nutrition intake is essential for human beings and influences various physiological and pathological actions in the human body. Among various nutritional factors, dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) has been shown to have various beneficial effects against inflammatory diseases. In addition to their therapeutic potency against inflammation, omega-3 PUFAs have also been shown to have anti-tumor effects via various mechanisms, such as cell arrest and apoptosis. To date, limited information is available on these effects in cutaneous malignancies. In this review, we focused on the effect of omega-3 PUFAs on skin cancers, especially malignant melanoma, basal cell carcinoma, lymphoma, and squamous cell carcinoma and discussed the detailed molecular mechanism of the omega-3 PUFA-mediated anti-tumor response. We also explored the molecular mechanisms mediated by epigenetic modifications, cell adhesion molecules, and anti-tumor immune responses. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Oncogenesis signaling of malignant melanoma and possible roles of omega-3 PUFAs. BRAF plays a role in MAPK pathway activation, which regulates the development of tumor cells, such as apoptosis, cell growth, and proliferation. NRAS mutations are related to the regulation of PI3K. Ultraviolet light exposure dysregulates p53 expression, leading to the suppression of tumor cell apoptosis.</p>
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<p>Oncogenesis signaling of basal cell carcinoma and possible roles of omega-3 PUFAs. As the detailed oncogenesis of basal cell carcinoma, hedgehog pathway gene mutation activates patched homolog and smoothened homolog, which are responsible for the development of basal cell carcinoma. P53 is suppressed by ultraviolet light exposure, leading to the suppression of apoptosis of basal cell carcinoma.</p>
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<p>Oncogenesis signaling of squamous cell carcinoma and possible roles of omega-3 PUFAs. P53 gene mutation is a crucial step in the development of cutaneous squamous cell carcinoma. P53 is responsible for cell apoptosis, DNA repair, and cell cycle arrest in squamous cell carcinoma. In addition, EGFR-mediated PI3K/AKT signaling and NRAS/RAF/MEK/ERK signaling also contribute to the development of squamous cell carcinoma.</p>
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12 pages, 6575 KiB  
Review
Diagnosis and Management of Inborn Errors of Metabolism in Adult Patients in the Emergency Department
by Isabel Solares, Carlos Heredia-Mena, Francisco Javier Castelbón, Daniel Jericó, Karol Marcela Córdoba, Antonio Fontanellas, Rafael Enríquez de Salamanca and Montserrat Morales-Conejo
Diagnostics 2021, 11(11), 2148; https://doi.org/10.3390/diagnostics11112148 - 19 Nov 2021
Cited by 6 | Viewed by 8616
Abstract
Inborn errors of metabolism (IEM) constitute an important group of conditions characterized by an altered metabolic pathway. There are numerous guidelines for the diagnosis and management of IEMs in the pediatric population but not for adults. Given the increasing frequency of this group [...] Read more.
Inborn errors of metabolism (IEM) constitute an important group of conditions characterized by an altered metabolic pathway. There are numerous guidelines for the diagnosis and management of IEMs in the pediatric population but not for adults. Given the increasing frequency of this group of conditions in adulthood, other clinicians in addition to pediatricians should be aware of them and learn to identify their characteristic manifestations. Early recognition and implementation of an appropriate therapeutic approach would improve the clinical outcome of many of these patients. This review presents when and how to investigate a metabolic disorder with the aim of encouraging physicians not to overlook a treatable disorder. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>How to address a suspected inborn error of metabolism error in the emergency department.</p>
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<p>Inborn errors of metabolism nosological classification.</p>
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<p>IEM classification according to symptoms.</p>
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<p>Recommendation of an hyperammonemia approach in the emergency department.</p>
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<p>Recommended approach for the acute porphyria attack in the emergency department.</p>
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16 pages, 4040 KiB  
Article
Improving Skin Cancer Classification Using Heavy-Tailed Student T-Distribution in Generative Adversarial Networks (TED-GAN)
by Bilal Ahmad, Sun Jun, Vasile Palade, Qi You, Li Mao and Mao Zhongjie
Diagnostics 2021, 11(11), 2147; https://doi.org/10.3390/diagnostics11112147 - 19 Nov 2021
Cited by 32 | Viewed by 4503
Abstract
Deep learning has gained immense attention from researchers in medicine, especially in medical imaging. The main bottleneck is the unavailability of sufficiently large medical datasets required for the good performance of deep learning models. This paper proposes a new framework consisting of one [...] Read more.
Deep learning has gained immense attention from researchers in medicine, especially in medical imaging. The main bottleneck is the unavailability of sufficiently large medical datasets required for the good performance of deep learning models. This paper proposes a new framework consisting of one variational autoencoder (VAE), two generative adversarial networks, and one auxiliary classifier to artificially generate realistic-looking skin lesion images and improve classification performance. We first train the encoder-decoder network to obtain the latent noise vector with the image manifold’s information and let the generative adversarial network sample the input from this informative noise vector in order to generate the skin lesion images. The use of informative noise allows the GAN to avoid mode collapse and creates faster convergence. To improve the diversity in the generated images, we use another GAN with an auxiliary classifier, which samples the noise vector from a heavy-tailed student t-distribution instead of a random noise Gaussian distribution. The proposed framework was named TED-GAN, with T from the t-distribution and ED from the encoder-decoder network which is part of the solution. The proposed framework could be used in a broad range of areas in medical imaging. We used it here to generate skin lesion images and have obtained an improved classification performance on the skin lesion classification task, rising from 66% average accuracy to 92.5%. The results show that TED-GAN has a better impact on the classification task because of its diverse range of generated images due to the use of a heavy-tailed t-distribution. Full article
(This article belongs to the Special Issue Intelligent Data Analysis for Medical Diagnosis)
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<p>Encoder-decoder of VAE is swapped after the training so that output noise from the decoder could be used as an input to the generator of GAN<sub>1</sub>. The figure represents the VAE and the GAN<sub>1</sub> of the proposed methodology. It’s a partial block diagram representation of the proposed TED-GAN.</p>
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<p>The generative adversarial network, GAN<sub>2</sub>, of the proposed framework and the auxiliary classifier. GAN<sub>2</sub> samples the input noise vector from student t-distribution and uses the images generated by GAN<sub>1</sub> for training. Generated images are passed through a high pass filter to improve imperceptibility.</p>
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<p>↑, ↓, BS, FC, BN, and O/P indicate upsampling, downsampling batch size, fully connected layer, batch normalization, and output, respectively. (<b>a</b>) The architecture of Generative adversarial networks used in this study. (<b>b</b>) Variational autoencoder architecture.</p>
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<p>The architecture of a CNN classifier is used to test the classification performance of different generative models. Here P, Max. P, F, and S represent the parameters, maximum pooling, number of filters, and filter size, respectively.</p>
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<p>Artificially generated images of most swear type of skin cancer, melanoma by GANS. The top left, right, and bottom blocks of images represent the melanoma images generated by GAN, DeLiGAN, and TED-GAN (proposed), respectively. By having a close look at upper two blocks of images, we can observe the repetition of generated images. The green, blue, and yellow blocks contain similar images. Diversity in the images can clearly be observed visually in the proposed block (bottom one).</p>
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<p>Features visualization of original and generated melanoma images. Upper and lower rows (original and generated images, respectively) represent the features that the convolutional layer of the classifier learned during the training process.</p>
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<p>Confusion matrices of various generative models. (<b>a</b>) (<b>A</b>)—Confusion matrix of the CNN classifier when trained only on HAM10000 images without any generative image. (<b>B</b>)—When classifier training includes the HAM10000 training set and the images generated by GAN [<a href="#B15-diagnostics-11-02147" class="html-bibr">15</a>]. (<b>C</b>)—When classifier includes HAM10000 training set and the images generated by DeLiGAN. (<b>D</b>)— When classifier training includes the HAM10000 training set and the images generated by proposed TED-GAN. (<b>b</b>) Training loss of the generator of TED-GAN (GAN<sub>2</sub>).</p>
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27 pages, 872 KiB  
Review
Primary Psychosis: Risk and Protective Factors and Early Detection of the Onset
by Claudio Brasso, Benedetta Giordano, Cristina Badino, Silvio Bellino, Paola Bozzatello, Cristiana Montemagni and Paola Rocca
Diagnostics 2021, 11(11), 2146; https://doi.org/10.3390/diagnostics11112146 - 19 Nov 2021
Cited by 19 | Viewed by 6284
Abstract
Primary psychosis, which includes schizophrenia and other psychoses not caused by other psychic or physical conditions, has a strong impact worldwide in terms of disability, suffering and costs. Consequently, improvement of strategies to reduce the incidence and to improve the prognosis of this [...] Read more.
Primary psychosis, which includes schizophrenia and other psychoses not caused by other psychic or physical conditions, has a strong impact worldwide in terms of disability, suffering and costs. Consequently, improvement of strategies to reduce the incidence and to improve the prognosis of this disorder is a current need. The purpose of this work is to review the current scientific literature on the main risk and protective factors of primary psychosis and to examine the main models of prevention, especially those related to the early detection of the onset. The conditions more strongly associated with primary psychosis are socio-demographic and economic factors such as male gender, birth in winter, ethnic minority, immigrant status, and difficult socio-economic conditions while the best-established preventive factors are elevated socio-economic status and an economic well-being. Risk and protective factors may be the targets for primordial, primary, and secondary preventive strategies. Acting on modifiable factors may reduce the incidence of the disorder or postpone its onset, while an early detection of the new cases enables a prompt treatment and a consequential better prognosis. According to this evidence, the study of the determinants of primary psychosis has a pivotal role in designing and promoting preventive policies aimed at reducing the burden of disability and suffering of the disorder. Full article
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<p>PRISMA flow-chart. * No automation tools were used. From: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews [<a href="#B12-diagnostics-11-02146" class="html-bibr">12</a>].</p>
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<p>Interplay between risk and protective factors, prevention, early detection of the onset, and outcomes. DOI: duration of illness; DUP: duration of untreated psychosis. The figure shows how acting on risk and protective factors through prevention (horizontal arrow) and through an early detection of the onset (vertical arrow), is it possible to reduce the incidence, the DOI and the DUP of primary psychosis. This allows ameliorating the prognosis and lowering the global burden of disability of the disease (not shown).</p>
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10 pages, 829 KiB  
Article
The Assessment of Nipple Areola Complex Sensation with Semmes-Weinstein Monofilaments—Normative Values and Its Covariates
by Anna Kasielska-Trojan, Agata Szulia, Tomasz Zawadzki and Bogusław Antoszewski
Diagnostics 2021, 11(11), 2145; https://doi.org/10.3390/diagnostics11112145 - 19 Nov 2021
Cited by 8 | Viewed by 14892
Abstract
Objective: To establish normative data for nipple-areola complex (NAC) sensibility examined with Semmes-Weinstein monofilament test (SWMT) and two-point discrimination (TPD) in women with varying breast sizes, including women with gigantomastia. We also aimed to identify clinical variables influencing NAC sensation. Methods: A total [...] Read more.
Objective: To establish normative data for nipple-areola complex (NAC) sensibility examined with Semmes-Weinstein monofilament test (SWMT) and two-point discrimination (TPD) in women with varying breast sizes, including women with gigantomastia. We also aimed to identify clinical variables influencing NAC sensation. Methods: A total of 320 breasts in 160 Caucasian women (mean age 33.6 years, SD 11 years) were examined (including 50 hypertrophic breasts). NACs sensation was examined using Semmes-Weinstein monofilaments (SWM) and the Weber Two-Point Discrimination Test. Results: The nipple appeared to be the most sensitive part of NAC. In normal-sized breasts, sensation thresholds (SWM) correlated with: age, BMI, history of births, breast size and ptosis (for all locations), breastfeeding history (for nipple and upper areola) and areola diameter (for all locations apart from the nipple). Regression analysis showed that age, cup size and suprasternal notch-to-nipple distance are risk factors for diminished NAC sensation. Sensation thresholds in all NAC locations of hypertrophic breasts were significantly higher compared to normal-sized breasts, while TPD tests did not differ between the groups. Conclusions: We provided normative values of NAC sensation (tactile threshold and TPD) for different NAC areas. Our investigation indicated that SWM are useful diagnostic tools when the following factors are considered while examining NAC sensation: location (nipple vs. areola), age, breast size, suprasternal notch-to-nipple distance, history of births and breastfeeding. Hypertrophic breasts presented significantly higher sensation thresholds for all NAC locations. The report may serve as a reference data for further investigations regarding NAC sensation after different breast surgeries. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Five NAC areas measured for sensation thresholds with SWMs. The measured points 1 cm from the nipple margin were labeled: Ni = nipple, Up = upper, Lo = lower, Me = medial, La = lateral.</p>
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<p>Four NAC areas measured for two-point discrimination with Weber esthesiometer. The most central points of esthesiometer placed 1 cm from the nipple margin were labeled: Up2 = upper, Lo2 = lower, Me2 = medial, La2 = lateral. *—distal point of esthesiometer arm when two-point touch was detected, X—the result of examination.</p>
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17 pages, 3697 KiB  
Case Report
Multidisciplinary In-Depth Investigation in a Young Athlete Suffering from Syncope Caused by Myocardial Bridge
by Mariarita Brancaccio, Cristina Mennitti, Arturo Cesaro, Emanuele Monda, Valeria D’Argenio, Giorgio Casaburi, Cristina Mazzaccara, Annaluisa Ranieri, Fabio Fimiani, Ferdinando Barretta, Fabiana Uomo, Martina Caiazza, Michele Lioncino, Giovanni D’Alicandro, Giuseppe Limongelli, Paolo Calabrò, Daniela Terracciano, Barbara Lombardo, Giulia Frisso and Olga Scudiero
Diagnostics 2021, 11(11), 2144; https://doi.org/10.3390/diagnostics11112144 - 19 Nov 2021
Cited by 11 | Viewed by 3260
Abstract
Laboratory medicine, along with genetic investigations in sports medicine, is taking on an increasingly important role in monitoring athletes’ health conditions. Acute or intense exercise can result in metabolic imbalances, muscle injuries or reveal cardiovascular disorders. This study aimed to monitor the health [...] Read more.
Laboratory medicine, along with genetic investigations in sports medicine, is taking on an increasingly important role in monitoring athletes’ health conditions. Acute or intense exercise can result in metabolic imbalances, muscle injuries or reveal cardiovascular disorders. This study aimed to monitor the health status of a basketball player with an integrated approach, including biochemical and genetic investigations and advanced imaging techniques, to shed light on the causes of recurrent syncope he experienced during exercise. Biochemical analyses showed that the athlete had abnormal iron, ferritin and bilirubin levels. Coronary Computed Tomographic Angiography highlighted the presence of an intramyocardial bridge, suggesting this may be the cause of the observed syncopes. The athlete was excluded from competitive activity. In order to understand if this cardiac malformation could be caused by an inherited genetic condition, both array-CGH and whole exome sequencing were performed. Array-CGH showed two intronic deletions involving MACROD2 and COMMD10 genes, which could be related to a congenital heart defect; whole exome sequencing highlighted the genotype compatible with Gilbert syndrome. However, no clear pathogenic mutations related to the patient’s cardiological phenotype were detected, even after applying machine learning methods. This case report highlights the importance and the need to provide exhaustive personalized diagnostic work up for the athletes in order to cover the cause of their malaise and for safeguarding their health. This multidisciplinary approach can be useful to create ad personam training and treatments, thus avoiding the appearance of diseases and injuries which, if underestimated, can become irreversible disorders and sometimes can result in the death of the athlete. Full article
(This article belongs to the Special Issue Diagnostic Challenges in Sports Cardiology)
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<p>Representative images of the electrocardiogram. (<b>A</b>) Representation of the three electrocardiograms performed, the first at rest (Line 1) and the other two under exercise (Line 2 and 3). (<b>B</b>) Representative ECG cycles taken at rest (column 1) and during exercise (column 2 and 3).</p>
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<p>Representative images of the electrocardiogram. (<b>A</b>) Representation of the three electrocardiograms performed, the first at rest (Line 1) and the other two under exercise (Line 2 and 3). (<b>B</b>) Representative ECG cycles taken at rest (column 1) and during exercise (column 2 and 3).</p>
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<p>(<b>A</b>,<b>B</b>) Representative images of the intramyocardial bridge. (<b>C</b>) Examination performed with CTA and 128 × 2 by gating scanner, dual source, gantry rotation time 280 ms, collimation thickness 0.6mm, during injection of iodate i.v. with multiplanar reconstruction, cMPR (Multi Planar Reformation), MIP (Maximum Intensity Projection) and 3D volume rendering. Double reading exam. Reference standard for SCCT/SIRM international guidelines.</p>
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<p>(<b>A</b>,<b>B</b>) Representative images of the intramyocardial bridge. (<b>C</b>) Examination performed with CTA and 128 × 2 by gating scanner, dual source, gantry rotation time 280 ms, collimation thickness 0.6mm, during injection of iodate i.v. with multiplanar reconstruction, cMPR (Multi Planar Reformation), MIP (Maximum Intensity Projection) and 3D volume rendering. Double reading exam. Reference standard for SCCT/SIRM international guidelines.</p>
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<p>Array-CGH. The CGH analysis shows a heterozygous deletion on the 5 chromosome at q23.1 region, partially including <span class="html-italic">COMMD10</span> gene (<b>left</b>) and a heterozygous deletion on the 20 chromosome at p12.1 region, partially including <span class="html-italic">MACROD2</span> and <span class="html-italic">MACROD2-AS1</span> genes (<b>right</b>).</p>
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<p>Oligogenic Combination Network. (<b>A</b>). Sixty-five genes had a median pathogenic score of ≥0.67. (<b>B</b>). Subset of network with highest median pathogenic score (≥89). Each node in the networks represent a gene reporting a pathogenic variant, while edges connect two genes only when there is at least one candidate disease-causing variant combination as predicted by VarCoPP. The colors of the edge represent the highest pathogenicity score for that pair and, more specifically, the highest Classification Score (CS) computed for a variant combination of that pair. This score is represented in a range from yellow (low pathogenicity score) to dark red (high pathogenicity score).</p>
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17 pages, 1384 KiB  
Review
Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management
by Tomas Simurda, Rosanna Asselta, Jana Zolkova, Monika Brunclikova, Miroslava Dobrotova, Zuzana Kolkova, Dusan Loderer, Ingrid Skornova, Jan Hudecek, Zora Lasabova, Jan Stasko and Peter Kubisz
Diagnostics 2021, 11(11), 2140; https://doi.org/10.3390/diagnostics11112140 - 19 Nov 2021
Cited by 38 | Viewed by 7982
Abstract
Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. The clinical phenotype is highly heterogeneous, being associated with bleeding, thrombosis, or absence of symptoms. Afibrinogenemia and hypofibrinogenemia are the consequence of mutations in [...] Read more.
Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. The clinical phenotype is highly heterogeneous, being associated with bleeding, thrombosis, or absence of symptoms. Afibrinogenemia and hypofibrinogenemia are the consequence of mutations in the homozygous, heterozygous, or compound heterozygous state in one of three genes encoding the fibrinogen chains, which can affect the synthesis, assembly, intracellular processing, stability, or secretion of fibrinogen. In addition to standard coagulation tests depending on the formation of fibrin, diagnostics also includes global coagulation assays, which are effective in monitoring the management of replacement therapy. Genetic testing is a key point for confirming the clinical diagnosis. The identification of the precise genetic mutations of congenital fibrinogen disorders is of value to permit early testing of other at risk persons and better understand the correlation between clinical phenotype and genotype. Management of patients with afibrinogenemia is particularly challenging since there are no data from evidence-based medicine studies. Fibrinogen concentrate is used to treat bleeding, whereas for the treatment of thrombotic complications, administered low-molecular-weight heparin is most often. This review deals with updated information about afibrinogenemia and hypofibrinogenemia, contributing to the early diagnosis and effective treatment of these disorders. Full article
(This article belongs to the Special Issue New Assays in the Diagnosis of Coagulation Protein Disorders)
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<p>Worldwide distribution of RBDs derived from the WFH survey 2019.</p>
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<p>Characterization of clinical phenotype in patients with quantitative fibrinogen disorders.</p>
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<p>Linear correlation (r = 0.9016; <span class="html-italic">p</span> &lt; 0.0001) between PT-derived fibrinogen and fibrinogen Clauss assay in patients with hypofibrinogenemia according to the study published by Skornova et al.</p>
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<p>Rotational thromboelastometry (EXTEM, INTEM, FIBTEM) results and fibrinogen activity in the patient with afibrinogenemia from our center. (<b>A</b>) Basal level; (<b>B</b>) 30 min after administration of 24 mg/kg fibrinogen concentrate (Haemocomplettan<sup>®</sup> P.</p>
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10 pages, 269 KiB  
Review
Serum Biomarkers in Carotid Artery Disease
by Vassiliki I. Kigka, Vassiliki Potsika, Michalis Mantzaris, Vassilis Tsakanikas, Igor Koncar and Dimitrios I. Fotiadis
Diagnostics 2021, 11(11), 2143; https://doi.org/10.3390/diagnostics11112143 - 18 Nov 2021
Cited by 12 | Viewed by 2622
Abstract
Carotid artery disease is considered a major cause of strokes and there is a need for early disease detection and management. Although imaging techniques have been developed for the diagnosis of carotid artery disease and different imaging-based markers have been proposed for the [...] Read more.
Carotid artery disease is considered a major cause of strokes and there is a need for early disease detection and management. Although imaging techniques have been developed for the diagnosis of carotid artery disease and different imaging-based markers have been proposed for the characterization of atherosclerotic plaques, there is still need for a definition of high-risk plaques in asymptomatic patients who may benefit from surgical intervention. Measurement of circulating biomarkers is a promising method to assist in patient-specific disease management, but the lack of robust clinical evidence limits their use as a standard of care. The purpose of this review paper is to present circulating biomarkers related to carotid artery diagnosis and prognosis, which are mainly provided by statistical-based clinical studies. The result of our investigation showed that typical well-established inflammatory biomarkers and biomarkers related to patient lipid profiles are associated with carotid artery disease. In addition to this, more specialized types of biomarkers, such as endothelial and cell adhesion, matrix degrading, and metabolic biomarkers seem to be associated with different carotid artery disease outputs, assisting vascular specialists in selecting patients at high risk for stroke and in need of intervention. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
36 pages, 823 KiB  
Review
Borderline Personality Disorder: Risk Factors and Early Detection
by Paola Bozzatello, Claudia Garbarini, Paola Rocca and Silvio Bellino
Diagnostics 2021, 11(11), 2142; https://doi.org/10.3390/diagnostics11112142 - 18 Nov 2021
Cited by 29 | Viewed by 43489
Abstract
Personality disorders (PDs) exert a great toll on health resources, and this is especially true for borderline personality disorder (BPD). As all PDs, BPD arises during adolescence or young adulthood. It is therefore important to detect the presence of this PD in its [...] Read more.
Personality disorders (PDs) exert a great toll on health resources, and this is especially true for borderline personality disorder (BPD). As all PDs, BPD arises during adolescence or young adulthood. It is therefore important to detect the presence of this PD in its earlier stages in order to initiate appropriate treatment, thus ameliorating the prognosis of this condition. This review aims to highlight the issues associated with BPD diagnosis in order to promote its early detection and treatment. To do so, we conducted a search on PubMed database of current evidence regarding BPD early diagnosis, focusing on risk factors, which represent important conditions to assess during young patient evaluation, and on diagnostic tools that can help the clinician in the assessment process. Our findings show how several risk factors, both environmental and genetic/neurobiological, can contribute to the onset of BPD and help identify at-risk patients who need careful monitoring. They also highlight the importance of a careful clinical evaluation aided by psychometric tests. Overall, the evidence gathered confirms the complexity of BDP early detection and its crucial importance for the outcome of this condition. Full article
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<p>Adapted from Gunderson et al. 2018.</p>
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12 pages, 2104 KiB  
Article
Variation in Sagittal Alignment Parameters in Adult Patients before Spine Surgery: A Serial Imaging Study Using Antero-Posterior and Latero-Lateral Projections
by Hunjong Lim, Eugene Lee, Joon-Woo Lee, Bo-Ram Kim, Yusuhn Kang and Joong-Mo Ahn
Diagnostics 2021, 11(11), 2141; https://doi.org/10.3390/diagnostics11112141 - 18 Nov 2021
Viewed by 6286
Abstract
Sagittal parameters of the spine are closely related to the evaluation and treatment of spine disease. However, there has been little research on variations in preoperative sagittal spinal alignment. This study was conducted to assess the variation in sagittal spinal alignment on serial [...] Read more.
Sagittal parameters of the spine are closely related to the evaluation and treatment of spine disease. However, there has been little research on variations in preoperative sagittal spinal alignment. This study was conducted to assess the variation in sagittal spinal alignment on serial antero-posterior and latero-lateral projections (EOS imaging) in adult patients before spine surgery. The sagittal parameters of 66 patients were collected from two serial images. Comparison between the first and second sagittal parameters was evaluated using the Wilcoxon signed-rank test. Subgroup analysis was performed based on the time interval between radiographs, patient’s age, and type of surgery. The sagittal vertical axis (SVA) exhibited statistically significant changes (p = 0.023), with the mean SVA increasing statistically (61.7 mm vs. 73.6 mm) and standard deviation increasing (51.5 mm vs. 61.6 mm) in the second image. Subgroup analysis showed significant differences in SVA (p = 0.034) in patients with an interval of >3 months; statistical differences in borderline levels in the SVA (p = 0.049) were observed in patients aged >65 years. Other parameters did not show statistically significant differences, except for SVA. Furthermore, SVA differences were statistically significant with increases in the EOS interval (>3 months) and patient age (>65 years). Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>Measurements of sagittal parameters using the EOS imaging system. SVA (sagittal vertical axis), CL (cervical lordosis), TK (thoracic kyphosis), TL (thoracolumbar angle), LL (lumbar lordosis), SS (sacral slope), PT (pelvic tilt), PI (pelvic incidence), T1 slope (angle between a horizontal line and the superior endplate of T1), C2–C4 (Cobb’s angle between the inferior endplates of C2 and C4), and C4–T1 (Cobb’s angle between the inferior endplates of C2 and C4).</p>
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<p>Changes in the sagittal vertical axis (SVA, length of a horizontal line connecting the posterosuperior corner of S1 to vertical plumbline from center of the C7 vertebral body) and T1 slope (angle between a horizontal line and the superior endplate of T1) on serial EOS images. Radiographs of a representative patient showing significant changes in the sagittal vertical axis (SVA, yellow) and T1 slope (white). There was no significant change in thoracic kyphosis (TK, Cobb’s angle between the inferior endplates of C7 and T12, red), sacral slope (SS, angle between the superior plate of S1 and a horizontal line, green), and pelvic incidence (PI, angle between the line connecting the midpoint of the bicoxofemoral axis to the midpoint of the sacral plate and the line perpendicular to the sacral plate, blue) between the two EOS images (time interval between the first and second EOS images is 140 days, the patient underwent surgery 33 days after taking the second EOS).</p>
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11 pages, 256 KiB  
Review
Small-Bowel Capsule Endoscopy—Optimizing Capsule Endoscopy in Clinical Practice
by Fintan O’Hara and Deirdre McNamara
Diagnostics 2021, 11(11), 2139; https://doi.org/10.3390/diagnostics11112139 - 18 Nov 2021
Cited by 10 | Viewed by 2850
Abstract
The small bowel is the longest organ within the gastrointestinal tract. The emergence of small bowel capsule endoscopy (SBCE) over the last 20 years has revolutionized the investigation and diagnosis of small bowel pathology. Its utility as a non-invasive and well-tolerated procedure, which [...] Read more.
The small bowel is the longest organ within the gastrointestinal tract. The emergence of small bowel capsule endoscopy (SBCE) over the last 20 years has revolutionized the investigation and diagnosis of small bowel pathology. Its utility as a non-invasive and well-tolerated procedure, which can be performed in an outpatient setting, has made it a valuable diagnostic tool. The indications for SBCE include obscure gastrointestinal bleeding, small bowel Crohn’s disease, and, less frequently for screening in polyposis syndromes, celiac disease, or other small bowel pathology. Currently, there are several small bowel capsules on the market from different manufacturers; however, they share many technological features. The European Society of Gastrointestinal Endoscopy (ESGE) only recently developed a set of key quality indicators to guide quality standards in this area. Many of the technical aspects of capsule endoscopy still feature a degree of uncertainty in terms of optimal performance. Incomplete studies due to slow transit through the bowel, poor imaging secondary to poor preparation, and the risk of capsule retention remain frustrations in its clinical utility. Capsule review is a time-consuming process; however, artificial intelligence and machine learning offer opportunities to improve this. This narrative review examines our current standing in a number of these aspects and the potential to further the application of SBCE in order to maximize its diagnostic utility. Full article
(This article belongs to the Special Issue Capsule Endoscopy: Clinical Impacts and Innovation since 2001)
13 pages, 7420 KiB  
Article
Low-Dose PET Imaging of Tumors in Lung and Liver Regions Using Internal Motion Estimation
by Sang-Keun Woo, Byung-Chul Kim, Eun Kyoung Ryu, In Ok Ko and Yong Jin Lee
Diagnostics 2021, 11(11), 2138; https://doi.org/10.3390/diagnostics11112138 - 18 Nov 2021
Viewed by 1736
Abstract
Motion estimation and compensation are necessary for improvement of tumor quantification analysis in positron emission tomography (PET) images. The aim of this study was to propose adaptive PET imaging with internal motion estimation and correction using regional artificial evaluation of tumors injected with [...] Read more.
Motion estimation and compensation are necessary for improvement of tumor quantification analysis in positron emission tomography (PET) images. The aim of this study was to propose adaptive PET imaging with internal motion estimation and correction using regional artificial evaluation of tumors injected with low-dose and high-dose radiopharmaceuticals. In order to assess internal motion, molecular sieves imitating tumors were loaded with 18F and inserted into the lung and liver regions in rats. All models were classified into two groups, based on the injected radiopharmaceutical activity, to compare the effect of tumor intensity. The PET study was performed with injection of F-18 fluorodeoxyglucose (18F-FDG). Respiratory gating was carried out by external trigger device. Count, signal to noise ratio (SNR), contrast and full width at half maximum (FWHM) were measured in artificial tumors in gated images. Motion correction was executed by affine transformation with estimated internal motion data. Monitoring data were different from estimated motion. Contrast in the low-activity group was 3.57, 4.08 and 6.19, while in the high-activity group it was 10.01, 8.36 and 6.97 for static, 4 bin and 8 bin images, respectively. The results of the lung target in 4 bin and the liver target in 8 bin showed improvement in FWHM and contrast with sufficient SNR. After motion correction, FWHM was improved in both regions (lung: 24.56%, liver: 10.77%). Moreover, with the low dose of radiopharmaceuticals the PET image visualized specific accumulated radiopharmaceutical areas in the liver. Therefore, low activity in PET images should undergo motion correction before quantification analysis using PET data. We could improve quantitative tumor evaluation by considering organ region and tumor intensity. Full article
(This article belongs to the Special Issue The Use of Motion Analysis for Diagnostics)
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<p>The results of motion correction PET image. (<b>a</b>) The left side image represents no motion correction, and the right side is a motion correction image of the lung. (<b>b</b>) The left side of the PET image represents no motion correction in liver, and right side represents a motion correction image.</p>
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<p>Results of detected motion variation in lung and liver during the PET image acquisition.</p>
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<p>PET images of the molecular sieve in the lung region; (<b>a</b>) a static PET image, (<b>b</b>) a PET image corrected using a fiducial marker, (<b>c</b>) an image corrected using 3D VIBE MRI, (<b>d</b>) an image corrected using 2D FLASH MRI, (<b>e</b>) an image corrected using a 2D tagged MRI.</p>
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<p>Motion correction PET image and result of FWHM in vertical and horizontal directions in the lung. (<b>a</b>) No motion correction PET image, (<b>b</b>) motion corrected PET image.</p>
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<p>Motion correction PET image and result of FWHM in vertical and horizontal direction of liver. (<b>a</b>) No motion correction PET image, (<b>b</b>) motion corrected PET image.</p>
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<p>Gate number effects on the (<b>a</b>) count, (<b>b</b>) SNR, (<b>c</b>) contrast in high- and low-activity PET data.</p>
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<p>Detection of specific areas in liver. (<b>A</b>) Acquired CT data before PET scan, (<b>B</b>) Slice section of small animal, (<b>C</b>) high-activity PET image, (<b>D</b>) low-activity PET image.</p>
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