Diagnostics, Volume 10, Issue 9 (September 2020) – 127 articles

This study reviews the current status and future prospective of knowledge on the use of artificial intelligence for the prediction of spontaneous preterm labor and birth (“preterm birth” hereafter). The summary of review suggests that different machine learning approaches would be optimal for different types of data regarding the prediction of preterm birth: the artificial neural network, logistic regression and/or the random forest for numeric data; the support vector machine for electrohysterogram data; the recurrent neural network for text data; and the convolutional neural network for image data. The ranges of performance measures were 0.79–0.94 for accuracy, 0.22–0.97 for sensitivity, 0.86–1.00 for specificity, and 0.54–0.83 for the area under the receiver operating characteristic curve. The following maternal variables were reported to be major determinants of preterm birth: delivery and pregestational body mass index, age, parity, predelivery systolic and diastolic blood pressure, twins, below high school graduation, infant sex, prior preterm birth, progesterone medication history, upper gastrointestinal tract symptom, gastroesophageal reflux disease, Helicobacter pylori, urban region, calcium channel blocker medication history, gestational diabetes mellitus, prior cone biopsy, cervical length, myomas and adenomyosis, insurance, marriage, religion, systemic lupus erythematosus, hydroxychloroquine sulfate, and increased cerebrospinal fluid and reduced cortical folding due to impaired brain growth. Full article

Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS. Methods: this retrospective bicentric cohort study included 30 patients (f = 13, median age, 66.5 (48–81) years) with pretherapeutic [¹¹¹In-DTPA⁰]octreotide scintigraphy (Octreoscan^®). ASP of functional volumes of up to three leading lesions per patient (n = 74) was calculated after semiautomatic, background-adapted segmentation. Uni- and multivariable Cox regression regarding PFS for clinical factors and the maximum ASP per patient was obtained. Results: all 30 patients showed metachronous or progressive liver metastases. ASP, primary tumor site, metastases pattern, and prior peptide receptor radionuclide therapy (PRRT) were significantly associated with PFS in univariable Cox regression. Only ASP > 12.9% (hazard ratio (HR), 3.33; p = 0.024) and prior PRRT (HR, 0.35; p = 0.043) remained significant in multivariable Cox. Median PFS was 6.7 months for ASP > 12.9% (95% confidence interval (CI), 2.1–11.4 months) versus 14.4 (12.5–16.3) months for ASP ≤ 12.9% (log-rank, p = 0.028). Conclusion: pretherapeutic ASP of SSR positive lesions independently predicted PFS for treatment with everolimus in GEP-NET. ASP may supplement risk-benefit assessment before patient inclusion to treatment. Full article

Incidental findings (IFs) are well known in medical research and clinical practice as unexpected findings having potential health or reproductive importance for an individual. IFs are discovered under different contexts but do not fall within the aim of a study, and/or are unanticipated or unintentionally revealed, and/or are not the specific focus or target of the particular research or clinical query. Today, in forensic settings, we can consider as incidental findings all the information that is neither related to the cause of death nor to the dynamic of the event or the scope of the forensic investigation. The question whether and how professionals should consider traditional values as guiding notions in the reporting of IFs in the context of forensic assessments is the focus of this article. We propose a descriptive analysis, which focuses on the forensic field, describing forensic situations in which IFs may occur, and whether and to whom they may be disclosed. Some considerations will be provided regarding forensic experts concerning their moral commitment to warn relatives about IFs. Full article

The prognostic significance of tumor budding in colon cancer is unequivocally documented, and the recommendations of the International Tumor Budding Consensus Conference (ITBCC) are currently the accepted basis for its assessment. Up to now, it is unknown whether the general use of a supporting cytokeratin immunohistochemistry can improve the interobserver variability and prognostic significance. Six investigators with different levels of experience reassessed 229 cases of colon carcinoma (pT3/4, N+/−, M0) with a supporting cytokeratin immunohistochemistry. The results were compared to previous assessments, which have been performed only on H & E. Bd3 was significantly associated with the occurrence of distant metastases according to the assessments of three out of six investigators (p < 0.05). Only one single investigator reached significant results concerning the cancer specific survival (p = 0.01). The pairwise kappa values range between a poor and moderate level of agreement (range 0.17–0.45; median 0.21). In conclusion, the results show no superiority of the use of an additional cytokeratin immunohistochemistry compared to the conventional analysis on sole H & E slides. Therefore, the general supporting use of a cytokeratin immunohistochemical staining seems to be inadvisable in colon cancer in consideration of necessary resources and costs. Full article

Mesonephric adenocarcinoma is a rare tumor that is considered to develop from mesonephric remnants of the female genital tract. This tumor usually occurs in the lateral wall of the uterine cervix. Herein, we present an exceptionally rare case of mesonephric adenocarcinoma located in the uterine fundus. The tumor exhibited intense hypermetabolism on ¹⁸F-FDG PET/CT. Based on the characteristic histologic features and immunohistochemical phenotypes, the diagnosis of mesonephric adenocarcinoma was confirmed. The patient underwent hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection, and no lymph node or distant metastasis was identified. After 20 months of surveillance without adjuvant therapy, she remains free of relapse. Full article

An accurate estimation of body fat percentage (BF%) in patients who are overweight or obese is of clinical importance. In this study, we aimed to develop an easy-to-use BF% predictive equation based on body mass index (BMI) suitable for individuals in this population. A simplified prediction equation was developed and evaluated for validity using anthropometric measurements from 375 adults of both genders who were overweight or obese. Measurements were taken in the outpatient clinic of the Department of Nutrition and Dietetics at Beirut Arab University (Lebanon). A total of 238 participants were used for model building (training sample) and another 137 participants were used for evaluating validity (validation sample). The final predicted model included BMI and sex, with non-significant prediction bias in BF% of −0.017 ± 3.86% (p = 0.946, Cohen’s d = 0.004). Moreover, a Pearson’s correlation between measured and predicted BF% was strongly significant (r = 0.84, p < 0.05). We are presenting a model that accurately predicted BF% in 61% of the validation sample with an absolute percent error less than 10% and non-significant prediction bias (−0.028 ± 4.67%). We suggest the following equations: BF% _females = 0.624 × BMI + 21.835 and BF% _males = 1.050 × BMI − 4.001 for accurate BF% estimation in patients who are overweight or obese in a clinical setting in Lebanon. Full article

The aim of this study was to determine the conversion factors for the effective dose (ED) per dose length product (DLP) for various computed tomography (CT) protocols based on the 2007 recommendations of the International Commission on Radiological Protection (ICRP). CT dose data from 369 CT scanners and 13,625 patients were collected through a nationwide survey. Data from 3793 patients with a difference in height within 5% of computational human phantoms were selected to calculate ED and DLP. The anatomical CT scan ranges for 11 scan protocols (adult-10, pediatric-1) were determined by experts, and scan lengths were obtained by matching scan ranges to computational phantoms. ED and DLP were calculated using the NCICT program. For each CT protocol, ED/DLP conversion factors were calculated from ED and DLP. Estimated ED conversion factors were 0.00172, 0.00751, 0.00858, 0.01843, 0.01103, 0.02532, 0.01794, 0.02811, 0.02815, 0.02175, 0.00626, 0.00458, 0.00308, and 0.00233 mSv∙mGy⁻¹∙cm⁻¹ for the adult brain, intra-cranial angiography, C-spine, L-spine, neck, chest, abdomen and pelvis, coronary angiography, calcium scoring, aortography, and CT examinations of pediatric brain of <2 years, 4–6 years, 9–11 years, and 13–15 years, respectively. We determined ED conversion factors for 11 CT protocols using CT data obtained from a nationwide survey in Korea and Monte Carlo-based dose calculations. Full article

The aim of the present study was to evaluate breast cancer risk in women aged 40–45 years not included in the routine mammographic screening programme in the Czech Republic and to assess the suitability of the screening interval. Our cohort study was conducted using registry data of one mammography centre (Bulovka Hospital in Prague) between 1 January 2008 and 31 December 2017. The risk of breast cancer was evaluated using a positive predictive finding (PPF) corresponding to the Breast Imaging-Reporting and Data System (BI-RADS) scores of 4 and 5. The annual PPF incidence rate achieved 2.25 per 1000 women aged 40–45 years and was not significantly different from that (3.31) of women of 45–50 years of age as demonstrated by an adjusted hazard ratio of 0.75 (95% confidence interval: 0.42–1.33). It was found that a screening interval longer than 3 years increased the chance of PPF occurrence 1.7 times independently of the women’s age, signalling a risk of failure of early detection of breast cancer. The same PPF incidence rates both in women aged 40–45 years and in older ones indicates that even younger women should be eligible for enrolment in the routine mammographic screening programme in the Czech Republic. Full article

The aim of this study was to analyze results of stenting atrioseptostomy in patients with pulmonary arterial hypertension and a different level of risk for one-year mortality that is not well described. Patients that underwent atrioseptostomy with stenting were retrospectively divided in two groups: “intermediate” (n = 55) or “high” risk (n = 13), according to the 2015 ESC/ESR guideline. Results of atrioseptostomy were assessed during hospital period and at follow-up. Patients from “intermediate” risk group demonstrated lower mortality rate (10/55, vs. 6/13) during the course of the study period, as well as higher freedom from lung transplantation or Potts shunt. At discharge, patients of both groups presented improvement in functional class and mobility. Patients from “intermediate” risk group showed longer 6-min walking distance, and lower levels of brain natriuretic peptide. At the latest follow-up, stable position and full patency of stents with right-to-left or bidirectional shunt at atrial level and absence of syncope was confirmed in patients of both groups. Patients from the “intermediate” risk group demonstrated higher functional class, better performance of walking test, and lower levels of brain natriuretic peptide. Stenting atrioseptostomy reliably secured interatrial communication and improved clinical condition in patients with idiopathic pulmonary arterial hypertension. Mid-term results were better in “intermediate” risk group. Full article

Background: The aim of this study was to investigate the association between temporomandibular disorder (TMD) and migraine through a longitudinal follow-up study using population data from a national health screening cohort. Methods: This cohort study used data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015. Of the 514,866 participants, 3884 TMD patients were matched at a 1:4 ratio with 15,536 control participants. Crude models and models adjusted for obesity, smoking, alcohol consumption, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, and Charlson Comorbidity Index (CCI) scores were calculated. Chi-squared test, Kaplan–Meier analysis, and two-tailed log-rank test were used for statistical analysis. Stratified Cox proportional hazard models were used to assess hazard ratios (HR) and 95% confidence intervals (CIs) for migraine in both control groups. Results: The adjusted HR for migraine was 2.10 (95% CI: 1.81–2.44) in the TMD group compared to the control group, which was consistent in subgroup analyses according to age, sex, and Kaplan–Meier analysis. Conclusions: This study demonstrated that TMD patients have a higher risk of migraine. These results suggest that dentists can decrease the risk of migraine in TMD patients by managing TMD properly. Full article

Peripheral arterial disease (PAD) is a common manifestation of generalized atherosclerosis, which affects more than 200 million patients worldwide. Currently, there is no ideal biomarker for PAD risk stratification and diagnosis. The goal of this research was to investigate the levels of inflammation biomarkers and cystatin C and to explore their utility for the diagnosis of PAD. The study included 296 participants, distributed in two groups: 216 patients diagnosed with PAD and 80 patients without PAD as controls. All studied biomarker levels (C-reactive protein, CRP; fibrinogen; erythrocyte sedimentation rate, ESR; neopterin; beta 2-microglobulin, B2-MG; and cystatin C) were significantly higher in the PAD group and indirectly correlated with the ankle–brachial index (ABI). The final logistic regression model included an association of neopterin, fibrinogen, and cystatin C as the most efficient markers for the prediction of PAD diagnosis. When comparing the area under the curve (AUC) for all biomarkers, the value for neopterin was significantly higher than those of all the other analyzed biomarkers. In agreement with previous studies, this research shows that markers such as fibrinogen, CRP, ESR, B2-MG, and cystatin C have significant value for the diagnosis of PAD, and also clearly underlines the accuracy of neopterin as a leading biomarker in PAD prediction. Full article

Salivary alpha-amylase (sAA) is a marker of psychological stress and might also be a potential marker for pain-associated stress due its non-invasive, cost-effective, and stress-free collection. The current study aimed to investigate whether the levels of sAA are influenced by experimentally induced muscle pain. In this study, 26 healthy, pain-free and age-matched participants (23.8 ± 2.6 years) were included, 13 women and 13 men. Prior to the experiment, questionnaires assessing health and anxiety were completed. Muscle pain was then induced through intramuscular injection of 0.4 mL hypertonic saline (56.5 mg/mL) into the masseter muscle and unstimulated whole saliva samples were collected at baseline before injection, 2 min, and 15 min after injection. A commercially available colorimetric assay was used to analyze the sAA. Perceived pain and stress were assessed using a 0–100 Numeric Rating Scale for each sample. There were no significant differences in sAA levels prior and after injection of hypertonic saline (p > 0.05) although sAA levels showed a slight decrease during experimentally-induced muscle pain. However, a strong correlation was observed between self-reported pain and perceived level of stress during experimentally-induced muscle pain (r₂ = 0.744; p < 0.0001). Furthermore, there was a moderate correlation between the levels of sAA at baseline and during experimental pain (r₂ = 0.687; p < 0.0001). In conclusion, this study could not show any association between the levels of sAA and perceived pain and or/stress. However, since a significant strong correlation could be observed between perceived stress and pain intensity, this study indicates that experimentally-induced muscle pain could be used as a stress model. Full article

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide, and its incidence is on the rise. A small fraction of cancer stem cells was identified within the tumour bulk, which are regarded as cancer-initiating cells, possess self-renewal and propagation potential, and a key driver for tumour heterogeneity and disease progression. Cancer heterogeneity reduces the overall efficacy of chemotherapy and contributes to treatment failure and relapse. The cell-surface and subcellular biomarkers related to breast cancer stem cell (BCSC) phenotypes are increasingly being recognised. These biomarkers are useful for the isolation of BCSCs and can serve as potential therapeutic targets and prognostic tools to monitor treatment responses. Recently, the role of noncoding microRNAs (miRNAs) has extensively been explored as novel biomarker molecules for breast cancer diagnosis and prognosis with high specificity and sensitivity. An in-depth understanding of the biological roles of miRNA in breast carcinogenesis provides insights into the pathways of cancer development and its utility for disease prognostication. This review gives an overview of stem cells, highlights the biomarkers expressed in BCSCs and describes their potential role as prognostic indicators. Full article

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged. Full article

In recent years, significant advances have been made in the diagnosis and therapeutic management of hypertrophic cardiomyopathy (HCM) patients, which has led to an important improvement in their longevity and quality of life. The use of multimodality imaging has an essential role in the diagnosis, assessing the regional distribution and severity of the disease, with important prognostic implications. At the same time, imaging contributes to the identification of optimal treatment for patients with hypertrophic cardiomyopathy, whether it is pharmaceutical, interventional or surgical treatment. Novel pharmacotherapies (like myosin inhibitors), minimally invasive procedures (such as transcatheter mitral valve repair, high-intensity focused ultrasound or radiofrequency ablation) and gene-directed approaches, may soon become alternatives for HCM patients. However, there are only few data on the early diagnosis of patients with HCM, in order to initiate treatment as soon as possible, to reduce the risk of sudden cardiac death (SCD). The aim of our review is to highlight the advantages of contemporary imaging in choosing the optimal management strategies for HCM patients, considering the novel therapies which are currently applied or studied for these patients. Full article

Primary cardiac tumors are extremely rare, with an incidence of 0.001–0.03%. Twenty-five percent of these tumors are malignant, with sarcomas accounting for approximately 95%. Cardiac intimal sarcoma is the least reported subtype of primary cardiac sarcoma. These endocardial mesenchymal tumors most often arise from great arterial vessels, and are rarely located in the heart. They often present with an aggressive clinical course and have a poor prognosis, with surgical resection with achievement of free margins being the mainstay of treatment. This emphasizes the importance of an early, correct diagnosis and timely intervention. We report a 60-year-old Caucasian male with several former cardiac surgical procedures due to congenital aortic stenosis, presenting with functional mitral stenosis/insufficiency and left ventricular outflow tract obstruction (LVOTO) due to massive masses in the left ventricle and atrium of the heart. Hybrid imaging with 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography/computed tomography (2-[¹⁸F]FDG PET/CT) was performed prior to surgery to characterize the intracardiac masses and estimate tumor burden, as well as to identify a potential extracardiac primary malignancy. Full article

Background: The present study aims to evaluate the diagnostic accuracy between ultrasonography-guided fine-needle aspiration cytology (US-FNAC) and core needle biopsy (CNB) of axillary lymph nodes (ALNs) in patients with breast cancer through a meta-analysis and a diagnostic test accuracy (DTA) review. Methods: The present meta-analysis and DTA review included 67 eligible studies. The diagnostic accuracy of various preoperative assessments, including US-FNAC and CNB, was evaluated for ALNs assessments in patients with breast cancer. In addition, a subgroup analysis based on methods of cytologic preparation was performed. In the DTA review, the sensitivity, specificity, diagnostic odds ratio (OR) and area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve were calculated. Results: The diagnostic accuracy of the preoperative assessments of ALNs was 0.850 (95% confidence interval (CI) 0.833–0.866) for patients with breast cancer. The diagnostic accuracy of CNB was significantly higher than that of US-FNAC (0.896, 95% CI 0.844–0.932 vs. 0.844, 95% CI 0.825–0.862; p = 0.044 in a meta-regression test). In the subgroup analysis based on cytologic preparation, the diagnosis accuracies were 0.860, 0.861 and 0.859 for the methods of conventional smear, liquid-based preparation and cell block, respectively. In the DTA review, CNB showed higher sensitivity than US-FNAC (0.849 vs. 0.760). However, there was no difference in specificity between US-FNAC and CNB (0.997 vs. 1.000). US-FNAC with liquid-based preparation and CNB showed the highest diagnostic OR and AUC on the SROC, respectively. Conclusion: Both US-FNAC and CNB are useful in preoperative assessments of ALNs in patients with breast cancer. Although the most sensitive test was found to be CNB in this study, there was no difference in specificity between various preoperative evaluations and the application of US-FNAC or CNB may be impacted by various factors. Full article

Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s). Full article

[¹⁸F]-FDG-PET/CT ([¹⁸F]-fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)) is increasingly used as a diagnostic tool in suspected infectious or inflammatory conditions. Studies on the value of FDG-PET/CT in children are scarce. This study assesses the role of FDG-PET/CT in suspected infection or inflammation in children. In this multicenter cohort study, 64 scans in 59 children with suspected infection or inflammation were selected from 452 pediatric FDG-PET/CT scans, performed in five hospitals between January 2016 and August 2017. Main outcomes were diagnostic information provided by FDG-PET/CT for diagnostic scans and impact on clinical management for follow-up scans. Of these 64 scans, 50 were performed for primary diagnosis and 14 to monitor disease activity. Of the positive diagnostic scans, 23/27 (85%) contributed to establishing a diagnosis. Of the negative diagnostic scans, 8/21 (38%) contributed to the final diagnosis by narrowing the differential or by providing information on the disease manifestation. In all follow-up scans, FDG-PET/CT results guided management decisions. CRP was significantly higher in positive scans than in negative scans (p = 0.004). In 6% of diagnostic scans, relevant incidental findings were identified. In conclusion, FDG-PET/CT performed in children with suspected infection or inflammation resulted in information that contributed to the final diagnosis or helped to guide management decisions in the majority of cases. Prospective studies assessing the impact of FDG-PET/CT results on diagnosis and patient management using a structured diagnostic protocol are feasible and necessary. Full article

Computer-aided detection and diagnosis (CAD) systems have the potential to improve robustness and efficiency compared to traditional radiological reading of magnetic resonance imaging (MRI). Fully automated segmentation of the prostate is a crucial step of CAD for prostate cancer, but visual inspection is still required to detect poorly segmented cases. The aim of this work was therefore to establish a fully automated quality control (QC) system for prostate segmentation based on T2-weighted MRI. Four different deep learning-based segmentation methods were used to segment the prostate for 585 patients. First order, shape and textural radiomics features were extracted from the segmented prostate masks. A reference quality score (QS) was calculated for each automated segmentation in comparison to a manual segmentation. A least absolute shrinkage and selection operator (LASSO) was trained and optimized on a randomly assigned training dataset (N = 1756, 439 cases from each segmentation method) to build a generalizable linear regression model based on the radiomics features that best estimated the reference QS. Subsequently, the model was used to estimate the QSs for an independent testing dataset (N = 584, 146 cases from each segmentation method). The mean ± standard deviation absolute error between the estimated and reference QSs was 5.47 ± 6.33 on a scale from 0 to 100. In addition, we found a strong correlation between the estimated and reference QSs (rho = 0.70). In conclusion, we developed an automated QC system that may be helpful for evaluating the quality of automated prostate segmentations. Full article

Becker muscular dystrophy (BMD) is an X-linked recessive disorder caused by dystrophin gene mutations. The phenotype and evolution of this muscle disorder are extremely clinical variable. In the last years, circulating biomarkers have acquired remarkable importance in their use as noninvasive biological indicators of prognosis and in monitoring muscle disease progression, especially when associated to muscle MRI imaging. We investigated the levels of circulating microRNAs (myo-miRNAs and inflammatory miRNAs) and of the proteins follistatin (FSTN) and myostatin (GDF-8) and compared results with clinical and radiological imaging data. In eight BMD patients, including two cases with evolving lower extremity weakness treated with deflazacort, we evaluated the expression level of 4 myo-miRNAs (miR-1, miR-206, miR-133a, and miR-133b), 3 inflammatory miRNAs (miR-146b, miR-155, and miR-221), FSTN, and GDF-8 proteins. In the two treated cases, there was pronounced posterior thigh and leg fibrofatty replacement assessed by muscle MRI by Mercuri score. The muscle-specific miR-206 was increased in all patients, and inflammatory miR-221 and miR-146b were variably elevated. A significant difference in myostatin expression was observed between steroid-treated and untreated patients. This study suggests that microRNAs and myostatin protein levels could be used to better understand the progression and management of the disease. Full article

Background: The aortic root diameter (AoD) has been shown to be a marker of cardiovascular risk and heart failure (HF). Data regarding the normal reference ranges in Asians and their correlates with diastolic dysfunction using contemporary guidelines remain largely unexplored. Methods: Among 5343 consecutive population-based asymptomatic Asians with echocardiography evaluations for aortic root diameter (without/with indexing, presented as AoD/AoDi) were related to cardiac structure/function and N-terminal pro-brain B-type natriuretic peptide (Nt-ProBNP), with 245 participants compared with multidetector computed tomography (MDCT)-based aortic root geometry. Results: Advanced age, hypertension, higher diastolic blood pressure, and lower body fat all contributed to greater AoD/AoDi. The highest correlation between echo-based aortic diameter and the MDCT-derived measures was found at the level of the aortic sinuses of Valsalva (r = 0.80, p < 0.001). Age- and sex-stratified normative ranges of AoD/AoDi were provided in 3646 healthy participants. Multivariate linear regressions showed that AoDi was associated with a higher NT-proBNP, more unfavorable left ventricular (LV) remodeling, worsened LV systolic annular velocity (TDI-s′), a higher probability of presenting with LV hypertrophy, and abnormal LV diastolic indices except tricuspid regurgitation velocity by contemporary diastolic dysfunction (DD) criteria (all p < 0.05). AoDi superimposed on key clinical variables significantly expanded C-statistic from 0.71 to 0.84 (p for ∆AUROC: < 0.001). These associations were broadly weaker for AoD. Conclusion: In our large asymptomatic Asian population, echocardiography-defined aortic root dilation was associated with aging and hypertension and were correlated modestly with computed tomography measures. A larger indexed aortic diameter appeared to be a useful indicator in identifying baseline abnormal diastolic dysfunction. Full article

(1) Background: To evaluate the characteristics of fluorescein breakup patterns (FBUPs) among patients with dry eye disease (DED) and efficacy of FBUPs as a diagnostic test for DED subgroups. (2) Methods: The study enrolled 449 patients with DED. FBUPs were categorized as follows: area break (AB), line break (LB), spot break (SB), dimple break (DB), and random break (RB). Schirmer value, fluorescein breakup time (FBUT), keratoconjunctival score, DED subgroups and subjective symptoms were examined. (3) Results: LB patients presented with short FBUT and high keratoconjunctival score. AB patients presented with short FBUT, high cornea and keratoconjunctival scores. SB patients were young with short FBUT. DB patients exhibited low keratoconjunctival score. RB patients were young, with long FBUT and low keratoconjunctival scores. Among DED subgroups, LB and AB constituted 74.7% of aqueous-deficiency dry eye (ADDE). SB and DB constituted 42.4% of short FBUT dry eye (short FBUT-DE). Post-test probabilities and positive likelihood ratios for ADDE were 58.7% and 1.63, respectively; those for short FBUT-DE were 46.3% and 2.02, respectively. Patients with SB and AB exhibited significantly severe subjective symptoms than other FBUPs. (4) Conclusions: FBUPs are associated with both objective findings and symptoms of DED and may be a clinical tool for identification of DED subgroups. Full article

Dental implant surgery is a common treatment for missing teeth. Its survival rate is considerably affected by host bone quality and quantity, which is often assessed prior to surgery through dental cone-beam computed tomography (CBCT). Dental CBCT was used in this study to evaluate dental implant sites for (1) differences in and (2) correlations between cancellous bone density and cortical bone thickness among four regions of the jawbone. In total, 315 dental implant sites (39 in the anterior mandible, 42 in the anterior maxilla, 107 in the posterior mandible, and 127 in the posterior maxilla) were identified in dental CBCT images from 128 patients. All CBCT images were loaded into Mimics 15.0 to measure cancellous bone density (unit: grayscale value (GV) and cortical bone thickness (unit: mm)). Differences among the four regions of the jawbone were evaluated using one-way analysis of variance and Scheffe’s posttest. Pearson coefficients for correlations between cancellous bone density and cortical bone thickness were also calculated for the four jawbone regions. The results revealed that the mean cancellous bone density was highest in the anterior mandible (722 ± 227 GV), followed by the anterior maxilla (542 ± 208 GV), posterior mandible (535 ± 206 GV), and posterior maxilla (388 ± 206 GV). Cortical bone thickness was highest in the posterior mandible (1.15 ± 0.42 mm), followed by the anterior mandible (1.01 ± 0.32 mm), anterior maxilla (0.89 ± 0.26 mm), and posterior maxilla (0.72 ± 0.19 mm). In the whole jawbone, a weak correlation (r = 0.133, p = 0.041) was detected between cancellous bone density and cortical bone thickness. Furthermore, except for the anterior maxilla (r = 0.306, p = 0.048), no correlation between the two bone parameters was observed (all p > 0.05). Cancellous bone density and cortical bone thickness varies by implant site in the four regions of the jawbone. The cortical and cancellous bone of a jawbone dental implant site should be evaluated individually before surgery. Full article

The aim of the present study is to evaluate the intra- and inter-observer agreement in assessing the renal function by means of ^99mTc-MAG3 diuretic renography. One hundred and twenty adults were enrolled in the study. One experienced and one junior radiographer processed the renograms twice by assigning manual and semi-automated regions of interest. The differential renal function (DRF, %), time to maximum counts for the right and left kidney (T_maxR-T_maxL, min) and time to half-peak counts (T_1/2, min) were calculated. The Bland–Altman analysis (bias±95% limits of agreement), Lin’s concordance correlation coefficient and weighted Fleiss’ kappa coefficient were used to assess agreement. Based on the Bland–Altman analysis, the intra-observer repeatability results for the experienced radiographer using the manual and the semi-automated techniques were 0.2 ± 2.6% and 0.3 ± 6.4% (DRF), respectively, −0.01 ± 0.24 and 0.00 ± 0.34 (T_maxR), respectively, and 0.00 ± 0.26 and 0.00 ± 0.33 (T_maxL), respectively. For the junior radiographer, the respective results were 0.5 ± 5.0% and 0.8 ± 9.4% (DRF), 0.00 ± 0.44 and 0.01 ± 0.28 (T_maxR), and 0.01 ± 0.28 and −0.02 ± 0.44 (T_maxL). The inter-observer repeatability for the manual method was 0.6 ± 5.0% (DRF), −0.10 ± 0.42 (T_maxR) and −0.05 ± 0.38 (T_maxL), and for the semi-automated method −0.2 ± 9.1% (DRF), 0.00 ± 0.31 (T_maxR) and −0.05 ± 0.40 (T_maxL). The weighted Fleiss’ kappa coefficient for the T_1/2 assessments ranged between 0.85–0.97 for both intra- and inter-observer repeatability with both methods. These findings suggest a very good repeatability in DRF assessment with the manual method—especially for the experienced observer—but a less good repeatability with the semi-automated approach. The calculation of T_max was also operator-dependent. We conclude that reader experience is important in the calculation of renal parameters. We therefore encourage reader training in renal scintigraphy. Moreover, the manual tool seems to perform better than the semi-automated tool. Thus, we encourage cautious use of automated tools and adjunct validation by manual methods where possible. Full article

Contrast-Enhanced Spectral Mammography (CESM) is a recently introduced mammographic method with characteristics particularly suitable for breast cancer radiomic analysis. This work aims to evaluate radiomic features for predicting histological outcome and two cancer molecular subtypes, namely Human Epidermal growth factor Receptor 2 (HER2)-positive and triple-negative. From 52 patients, 68 lesions were identified and confirmed on histological examination. Radiomic analysis was performed on regions of interest (ROIs) selected from both low-energy (LE) and ReCombined (RC) CESM images. Fourteen statistical features were extracted from each ROI. Expression of estrogen receptor (ER) was significantly correlated with variation coefficient and variation range calculated on both LE and RC images; progesterone receptor (PR) with skewness index calculated on LE images; and Ki67 with variation coefficient, variation range, entropy and relative smoothness indices calculated on RC images. HER2 was significantly associated with relative smoothness calculated on LE images, and grading tumor with variation coefficient, entropy and relative smoothness calculated on RC images. Encouraging results for differentiation between ER+/ER−, PR+/PR−, HER2+/HER2−, Ki67+/Ki67−, High-Grade/Low-Grade and TN/NTN were obtained. Specifically, the highest performances were obtained for discriminating HER2+/HER2− (90.87%), ER+/ER− (83.79%) and Ki67+/Ki67− (84.80%). Our results suggest an interesting role for radiomics in CESM to predict histological outcomes and particular tumors’ molecular subtype. Full article

Objectives: The distribution of venous pathology in stasis leg ulcers is unclear. The main reason for this uncertainty is the lack of objective diagnostic tools. To fill this gap, we assessed the effectiveness of triggered angiography non-contrast-enhanced (TRANCE)-magnetic resonance imaging (MRI) in determining the venous status of patients with stasis leg ulcers. Methods: This prospective observational study included the data of 23 patients with stasis leg ulcers who underwent TRANCE-MRI between April 2017 and May 2020; the data were retrospectively analyzed. TRANCE MRI utilizes differences in vascular signal intensity during the cardiac cycle for subsequent image subtraction, providing not only a venogram but also an arteriogram without the use of contrast agents or radiation. Results: TRANCE MRI revealed that the stasis leg ulcers of nine of the 23 patients could be attributed to valvular insufficiency and venous occlusion (including deep venous thrombosis [DVT], May–Thurner syndrome, and other external compression). Moreover, TRANCE MRI demonstrated no venous pathology in five patients (21.7%). We analyzed TRANCE MRI hemodynamic parameters, namely stroke volume, forward flow volume, backward flow volume, regurgitant fraction, absolute volume, mean flux, stroke distance, and mean velocity, in the external iliac vein, femoral vein, popliteal vein, and great saphenous vein (GSV) in three of the patients with valvular insufficiency and three of those with venous occlusion. We found that the mean velocity and stroke volume in the GSV was higher than that in the popliteal vein in all patients with venous valvular insufficiency. Conclusions: Stasis leg ulcers may have no underlying venous disease and could be confirmed by TRANCE-MRI. TRANCE MRI has good Interrater reliability between Duplex study in greater saphenous venous insufficiency. It also potentially surpasses existing diagnostic modalities in terms of distinguishable hemodynamic figures. Accordingly, TRANCE-MRI is a safe and useful tool for examining stasis leg ulcers and is extensively applied currently. Full article

Asherman syndrome is a multifaceted condition describing the partial or complete removal of the uterine cavity and/or cervical canal. It is a highly debatable topic because of its pronounced influence on both reproductive outcomes and gynaecologic symptoms. The latest reports demonstrated that trauma to the endometrium is the main cause of intrauterine adhesion formation. Left untreated, such adhesions gradually lead to a range of repercussions ranging from mild to severe. Considering the lack of non-invasive approaches, the advent of hysteroscopy has revolutionized the entire field, being otherwise considered the most efficient tool offering new directions and amplifying the chances of treating the Asherman syndrome. Full article

Chronic liver inflammation progressively evokes fibrosis and cirrhosis resulting in compromised liver function, and often leading to cancer. Early diagnosis and staging of fibrosis is crucial because the five-year survival rate of early-stage liver cancer is high. This study investigates the progression of hepatic fibrosis induced in rats following ingestion of diethylnitrosamine (DEN). Changes in oxygen saturation and hemoglobin concentration resulting from chronic inflammation were assayed longitudinally during DEN ingestion by photoacoustic imaging (PAI). Accompanying liver tissue changes were monitored simultaneously by B-mode sonographic imaging. Oxygen saturation and hemoglobin levels in the liver increased over 5 weeks and peaked at 10 weeks before decreasing at 13 weeks of DEN ingestion. The oxygenation changes were accompanied by an increase in hepatic echogenicity and coarseness in the ultrasound image. Histology at 13 weeks confirmed the development of severe fibrosis and cirrhosis. The observed increase in PA signal representing enhanced blood oxygenation is likely an inflammatory physiological response to the dietary DEN insult that increases blood flow by the development of neovasculature to supply oxygen to a fibrotic liver during the progression of hepatic fibrosis. Assessment of oxygenation by PAI may play an important role in the future assessment of hepatic fibrosis. Full article

This meta-analysis aimed to evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1), their associations with the clinicopathological characteristics, and the association between their levels in patients with triple-negative breast cancer (TNBC). PubMed, EMBASE, Scopus, ProQuest, Web of Science, and Cochrane Library databases were searched to obtain the relevant papers. Seven studies with 1152 patients were included in this study. Like the level of TILs, there were no significant associations between PD-L1 expression and tumor size, tumor stage, lymph node metastasis, histological grade, and Ki67 (All p-values ≥ 0.05). Furthermore, there was no significant association between PD-L1 expression with overall survival (OS) and disease-free survival (DFS). In assessment of TILs and survival relationship, the results showed that a high level of TILs was associated with long-term OS (hazard ratios (HR) = 0.48, 95% CI: 0.30 to 0.77, p-value < 0.001) and DFS (HR = 0.53, 95% CI: 0.35 to 0.78, p-value < 0.001). The results displayed that tumoral PD-L1 expression was strongly associated with high levels of TILs in TNBC patients (OR = 8.34, 95% CI: 2.68 to 25.95, p-value < 0.001). In conclusion, the study has shown the prognostic value of TILs and a strong association between tumoral PD-L1 overexpression with TILs in TNBC patients. Full article