Diagnostics

Introduction: The increasing usage of NGS technology has enabled the discovery of new causal genes in ciliopathies, including the DCDC2 gene. The aim of our study was to present the clinical, pathological and molecular report of six patients (from three unrelated families) with DCDC2 biallelic pathogenic variants. A detailed overview of the reported patients with DCDC2-related disease was provided. Material and methods: A retrospective chart review of the clinical, biochemical, pathological (liver histology) and molecular features of the study group was performed. The database PubMed (MEDLINE) was searched for relevant studies. Results: All the patients presented with cholestatic jaundice and elevated GGT; the mean age was 2 months. The initial liver biopsy was performed in four children at a mean age of 3 months (age range: 2–5 months). In all of them, features of cholestasis, portal fibrosis and mild portal inflammation were observed; in three of them ductular proliferation was observed. One patient had undergone liver transplantation (LTx) at 8 years of age. At hepatectomy, a biliary-pattern cirrhosis was observed. Only one patient presented with features of renal disease. Whole exome sequencing was performed in all patients at the last follow-up visit (mean age 10 years). Three different variants (one novel) in the DCDC2 gene were identified in the study group. With our six patients, a total of 34 patients with DCDC2-related hepatic ciliopathy were identified. The main clinical presentation of DCDC2-related ciliopathy was liver disease in the form of neonatal sclerosing cholangitis. The predominance of early and severe liver disease associated with no or mildly expressed kidney involvement was observed. Conclusions: Our findings expand the molecular spectrum of pathogenic DCDC2 variants, provide a more accurate picture of the phenotypic expression associated with molecular changes in this gene and confirm a loss of functional behaviour as the mechanism of disease. Full article

Medical data, such as electronic health records, are a repository for a patient’s medical records for use in the diagnosis of different diseases. Using medical data for individual patient care raises a number of concerns, including trustworthiness in data management, privacy, and patient data security. The introduction of visual analytics, a computing system that integrates analytics approaches with interactive visualizations, can potentially deal with information overload concerns in medical data. The practice of assessing the trustworthiness of visual analytics tools or applications using factors that affect medical data analysis is known as trustworthiness evaluation for medical data. It has a variety of major issues, such as a lack of important evaluation of medical data, the need to process much of medical data for diagnosis, the need to make trustworthy relationships clear, and the expectation that it will be automated. Decision-making strategies have been utilized in this evaluation process to avoid these concerns and intelligently and automatically analyze the trustworthiness of the visual analytics tool. The literature study found no hybrid decision support system for visual analytics tool trustworthiness in medical data diagnosis. Thus, this research develops a hybrid decision support system to assess and improve the trustworthiness of medical data for visual analytics tools using fuzzy decision systems. This study examined the trustworthiness of decision systems using visual analytics tools for medical data for the diagnosis of diseases. The hybrid multi-criteria decision-making-based decision support model, based on the analytic hierarchy process and sorting preferences by similarity to ideal solutions in a fuzzy environment, was employed in this study. The results were compared to highly correlated accuracy tests. In conclusion, we highlight the benefits of our proposed study, which includes performing a comparison analysis on the recommended models and some existing models in order to demonstrate the applicability of an optimal decision in real-world environments. In addition, we present a graphical interpretation of the proposed endeavor in order to demonstrate the coherence and effectiveness of our methodology. This research will also help medical experts select, evaluate, and rank the best visual analytics tools for medical data. Full article

Medulloblastomas, highly aggressive neoplasms of the central nervous system (CNS) that present significant heterogeneity in clinical presentation, disease course, and treatment outcomes, are common in childhood. Moreover, patients who survive may be diagnosed with subsequent malignancies during their life or could develop treatment-related medical conditions. Genetic and transcriptomic studies have classified MBs into four subgroups: wingless type (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4, with distinct histological and molecular profiles. However, recent molecular findings resulted in the WHO updating their guidelines and stratifying medulloblastomas into further molecular subgroups, changing the clinical stratification and treatment management. In this review, we discuss most of the histological, clinical, and molecular prognostic factors, as well the feasibility of their application, for better characterization, prognostication, and treatment of medulloblastomas. Full article

Lung adenocarcinoma (LUAD) is a rapidly progressive malignancy, and its mortality rate is very high. In this study, we aimed at finding novel prognosis-related genes and constructing a credible prognostic model to improve the prediction for LUAD patients. Differential gene expression, mutant subtype, and univariate Cox regression analyses were conducted with the dataset from the Cancer Genome Atlas (TCGA) database to screen for prognostic features. These features were employed in the following multivariate Cox regression analysis and the produced prognostic model included the stage and expression of SMCO2, SATB2, HAVCR1, GRIA1, and GALNT4, as well as mutation subtypes of TP53. The exactness of the model was confirmed by an overall survival (OS) analysis and disease-free survival (DFS) analysis, which indicated that patients in the high-risk group had a poorer prognosis compared to those in the low-risk group. The area under the receiver operating characteristic curve (AUC) was 0.793 in the training group and 0.779 in the testing group. The AUC of tumor recurrence was 0.778 in the training group and 0.815 in the testing group. In addition, the number of deceased patients increased as the risk scores raised. Furthermore, the knockdown of prognostic gene HAVCR1 suppressed the proliferation of A549 cells, which supports our prognostic model that the high expression of HAVCR1 predicts poor prognosis. Our work created a reliable prognostic risk score model for LUAD and provided potential prognostic biomarkers. Full article

Background: In vivo Hounsfield Unit (HU) values have traditionally been determined using direct CT image measurements. These measurements are dependent on the window/level used to examine the CT image and the individual conducting the fat tissue tracing. Methods: Using an indirect method, a new reference interval (RI) is proposed. A total of 4000 samples of fat tissues were collected from routine abdominal CT examinations. A linear regression equation was then calculated using the linear part of the cumulative frequency plot of their average values. Results: The regression function for total abdominal fat was determined to be y = 35.376*x − 123.48, and a 95% confidence RI of −123 to −89 was computed. A significant difference of 3.82 was observed between the average fat HU values of visceral and subcutaneous areas. Conclusions: Using statistical methods and the in vivo measurements of patient data, a series of RIs were determined for fat HU that is consistent with theoretical values. Full article

Renal cell carcinoma, an aggressive malignancy, is often incidentally diagnosed. The patient remains asymptomatic to the late stage of the disease, when the local or distant metastases are already present. Surgical treatment remains the choice for these patients, although the plan must adapt to the characteristics of the patients and the extension of the neoplasm. Systemic therapy is sometimes needed. It includes immunotherapy, target therapy, or both, with a high level of toxicity. Cardiac biomarkers have prognosis and monitoring values in this setting. Their role in postoperative identification of myocardial injury and heart failure already have been demonstrated, as well as their importance in preoperative evaluation from the cardiac point of view and the progression of renal cancer. The cardiac biomarkers are also part of the new cardio-oncologic approach to establishing and monitoring systemic therapy. They are complementary tests for assessment of the baseline toxicity risk and tools to guide therapy. The goal must be to continue the treatment as long as possible with the initiation and optimisation of the cardiological treatment. Cardiac atrial biomarkers are reported to have also antitumoral and anti-inflammatory properties. This review aims to present the role of cardiac biomarkers in the multidisciplinary management of renal cell carcinoma patients. Full article

Skin cancer is one the most dangerous types of cancer and is one of the primary causes of death worldwide. The number of deaths can be reduced if skin cancer is diagnosed early. Skin cancer is mostly diagnosed using visual inspection, which is less accurate. Deep-learning-based methods have been proposed to assist dermatologists in the early and accurate diagnosis of skin cancers. This survey reviewed the most recent research articles on skin cancer classification using deep learning methods. We also provided an overview of the most common deep-learning models and datasets used for skin cancer classification. Full article

Background: The purpose of the study was to assess the relationship between inflammatory biomarkers (NLR—neutrophil-to-lymphocyte ratio, PLR—platelet-to-lymphocyte ratio, LMR—lymphocyte-to-monocyte ratio, SII—systemic immune-inflammation index) and overall survival in gastric cancer patients. Methods: Over a six-year period (2016–2021), we conducted a longitudinal retrospective cohort research on 549 patients with resectable stomach adenocarcinoma. The overall survival was determined using the univariate and multivariate COX proportional hazards models. Results: The age of the cohort varied between 30 and 89 years old, with an average age of 64.85 ± 10.51 years. Four hundred seventy-six patients (86.7%) had R0 resection margins. Eighty-nine (16.21%) subjects received neoadjuvant chemotherapy. Two hundred sixty-two (47.72%) patients died during the follow-up period. The median survival time in the cohort was 390 days. A significantly lower (p = 0.029—Logrank test) median survival was observed for R1 resections (355 days) in comparison with R0 resections (395 days). Significant differences in survival were observed regarding tumor differentiation, tumoral (T), and node (N) stage. No differences in survival were observed between the low or high value of inflammatory biomarkers (dichotomized by median value in the sample). In the COX univariate and multivariate regression models, elevated NLR proved an independent prognostic factor for lower overall survival [HR = 1.068, (95% CI 1.011–1.12)]. In this study, the other inflammatory ratios (PLR, LMR, and SII) did not prove as prognostic factors for gastric adenocarcinoma. Conclusions: In resectable gastric adenocarcinoma, elevated NLR before surgery was associated with lower overall survival. PLR, LMR, and SII had no prognostic value for the patient’s survival. Full article

Cases of digestive cancers diagnosed during pregnancy are rare. The increasing prevalence of pregnancy in women aged 30–39 years (and not exceptionally 40–49 years) could explain the frequent co-occurrence of cancers and pregnancy. The diagnosis of digestive cancers in pregnancy is difficult due to the overlap between neoplasm symptomatology and the clinical picture of pregnancy. A paraclinical evaluation may also be difficult depending on the trimester of the pregnancy. Diagnosis is also delayed by practitioners’ hesitation to use invasive investigations (imaging, endoscopy, etc.) due to fetal safety concerns. Therefore, digestive cancers are often diagnosed during pregnancy in advanced stages, where complications such as occlusions, perforations, and cachexia have already arisen. In this review, we highlight the epidemiology, clinical aspects, paraclinical evaluation, and particularities of the diagnosis and treatment of gastric cancer during pregnancy. Full article

Transcatheter aortic valve implantation (TAVI) has become the standard of care in elderly high-risk patients with symptomatic severe aortic stenosis. Recently, TAVI has been increasingly performed in younger-, intermediate- and lower-risk populations, which underlines the need to investigate the long-term durability of bioprosthetic aortic valves. However, diagnosing bioprosthetic valve dysfunction after TAVI is challenging and only limited evidence-based criteria exist to guide therapy. Bioprosthetic valve dysfunction encompasses structural valve deterioration (SVD) resulting from degenerative changes in the valve structure and function, non-SVD resulting from intrinsic paravalvular regurgitation or patient–prosthesis mismatch, valve thrombosis, and infective endocarditis. Overlapping phenotypes, confluent pathologies, and their shared end-stage bioprosthetic valve failure complicate the differentiation of these entities. In this review, we focus on the contemporary and future roles, advantages, and limitations of imaging modalities such as echocardiography, cardiac computed tomography angiography, cardiac magnetic resonance imaging, and positron emission tomography to monitor the integrity of transcatheter heart valves. Full article

(1) Background: Uveal malignant melanoma is the most common adult eye cancer and presents metabolic reprogramming that affects the tumoral microenvironment by altering the redox balance and producing oncometabolites. (2) Methods: The study prospectively evaluated patients undergoing enucleation surgery or stereotactic radiotherapy for uveal melanoma by following systemic oxidative-stress redox markers serum lipid peroxides, total albumin groups and total antioxidant levels (3) Results: Serum antioxidants and lipid peroxides were elevated from pre-treatment to longer-term follow-up. Antioxidants inversely correlated to lipid peroxides: higher in stereotactic radiosurgery patients pre/6/12/18 months post-treatment (p = 0.001–0.049) versus higher lipid peroxides in enucleation surgery patients pre/after/6 months post-treatment (p = 0.004–0.010). An increased variance in serum antioxidants was observed for enucleation surgery patients (p < 0.001), however enucleation did not increase mean serum antioxidants or albumin thiols; only lipid peroxides were increased post-enucleation (p < 0.001) and at 6-month follow-up (p = 0.029). Mean albumin thiols were increased for 18- and 24-month follow-ups (p = 0.017–0.022). Males who had enucleation surgery presented higher variance in serum determinations and overall higher lipid peroxides values pre/post-treatment and at the 18-month follow-up. (4) Conclusions: Initial oxidative stress-inducing events of surgical enucleation or stereotactic radiotherapy for uveal melanoma are followed by a longer-term inflammatory cascade gradually subsiding at later follow-ups. Full article

Quality Control (QC) and Quality Assurance (QA) principles are essential for effective cervical cancer prevention. Being a crucial diagnostic step, colposcopy’s sensitivity and specificity improvements are strongly advocated worldwide since inter- and intra-observer differences are the main limiting factors. The objective of the present study was the evaluation of colposcopy accuracy through the results of a QC/QA assessment from a survey in Italian tertiary-level academic and teaching hospitals. A web-based, user-friendly platform based on 100 colposcopic digital images was forwarded to colposcopists with different levels of experience. Seventy-three participants were asked to identify colposcopic patterns, provide personal impressions, and indicate the correct clinical practice. The data were correlated with a panel of experts’ evaluation and with the clinical/pathological data of the cases. Overall sensitivity and specificity with the threshold of CIN2+ accounted for 73.7% and 87.7%, respectively, with minor differences between senior and junior candidates. Identification and interpretation of colposcopic patterns showed full agreement with the experts’ panel, ranging from 50% to 82%, in some instances with better results from junior colposcopists. Colposcopic impressions correlated with a 20% underestimation of CIN2+ lesions, with no differences linked to level of experience. Our results demonstrate the good diagnostic performance of colposcopy and the need for improving accuracy through QC assessments and adhesion to standard requirements and recommendations. Full article

COVID-19 is a multisystemic disease that mainly affects and causes dysregulation of the endothelium, causing systemic manifestations. A nailfold video capillaroscopy is a safe, easy, and noninvasive method to evaluate microcirculation alteration. In this review, we analyzed the literature available to date regarding the object of nailfold video capillaroscopy (NVC) use in patients with a SARS-CoV-2 infection, both in the acute phase and after discharge. The scientific evidence pointed out the main alterations in capillary circulation shown by NVC, so reviewing the findings of each article allowed us to define and analyze the future prospects and needs for possibly including NVC within the management of patients with COVID-19, both during and after the acute phase. Full article

Multiple studies presented satisfactory performances for the treatment of various ocular diseases. To date, there has been no study that describes a multiclass model, medically accurate, and trained on large diverse dataset. No study has addressed a class imbalance problem in one giant dataset originating from multiple large diverse eye fundus image collections. To ensure a real-life clinical environment and mitigate the problem of biased medical image data, 22 publicly available datasets were merged. To secure medical validity only Diabetic Retinopathy (DR), Age-Related Macular Degeneration (AMD) and Glaucoma (GL) were included. The state-of-the-art models ConvNext, RegNet and ResNet were utilized. In the resulting dataset, there were 86,415 normal, 3787 GL, 632 AMD and 34,379 DR fundus images. ConvNextTiny achieved the best results in terms of recognizing most of the examined eye diseases with the most metrics. The overall accuracy was 80.46 ± 1.48. Specific accuracy values were: 80.01 ± 1.10 for normal eye fundus, 97.20 ± 0.66 for GL, 98.14 ± 0.31 for AMD, 80.66 ± 1.27 for DR. A suitable screening model for the most prevalent retinal diseases in ageing societies was designed. The model was developed on a diverse, combined large dataset which made the obtained results less biased and more generalizable. Full article

Knee osteoarthritis (OA) detection is an important area of research in health informatics that aims to improve the accuracy of diagnosing this debilitating condition. In this paper, we investigate the ability of DenseNet169, a deep convolutional neural network architecture, for knee osteoarthritis detection using X-ray images. We focus on the use of the DenseNet169 architecture and propose an adaptive early stopping technique that utilizes gradual cross-entropy loss estimation. The proposed approach allows for the efficient selection of the optimal number of training epochs, thus preventing overfitting. To achieve the goal of this study, the adaptive early stopping mechanism that observes the validation accuracy as a threshold was designed. Then, the gradual cross-entropy (GCE) loss estimation technique was developed and integrated to the epoch training mechanism. Both adaptive early stopping and GCE were incorporated into the DenseNet169 for the OA detection model. The performance of the model was measured using several metrics including accuracy, precision, and recall. The obtained results were compared with those obtained from the existing works. The comparison shows that the proposed model outperformed the existing solutions in terms of accuracy, precision, recall, and loss performance, which indicates that the adaptive early stopping coupled with GCE improved the ability of DenseNet169 to accurately detect knee OA. Full article

This prospective pilot study aimed to evaluate whether cerebral inflow and outflow abnormalities assessed by ultrasonographic examination could be associated with recurrent benign paroxysmal positional vertigo (BPPV). Twenty-four patients with recurrent BPPV, affected by at least two episodes, and diagnosed according to American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) criteria, evaluated at our University Hospital, between 1 February 2020 and 30 November 2021, have been included. At the ultrasonographic examination, 22 of 24 patients (92%) reported one or more alterations of the extracranial venous circulation, among those considered for the diagnosis of chronic cerebrospinal venous insufficiency (CCSVI), although none of the studied patients were found to have alterations in the arterial circulation. The present study confirms the presence of alterations of the extracranial venous circulation in recurrent BPPV; these anomalies (such as stenosis, blockages or regurgitation of flow, or abnormal valves, as per the CCSVI) could cause a disruption in the venous inner ear drainage, hampering the inner ear microcirculation and then possibly causing recurrent otolith detachment. Full article

Background: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) can present with overlapping symptoms, making diagnosis and management challenging. Patients with IBD in remission may continue to experience IBS symptoms. Patients with IBS were found to have a disproportionately higher prevalence of abdominal and pelvic surgeries than the general population. Aims: The aim of this study was to determine whether IBS is a risk factor for undergoing surgical interventions in patients with IBD and explore the diagnostic implications of these findings. Methods: A population-based cohort analysis was performed using TriNetX. Patients with Crohn’s disease + IBS (CD + IBS) and ulcerative colitis + IBS (UC + IBS) were identified. The control groups consisted of patients with CD or UC alone without IBS. The main outcome was to compare the risks of undergoing surgical interventions between the cohorts. The secondary outcomes were to compare the risks of developing gastrointestinal symptoms and IBD-related complications between the cohorts. Results: Patients with IBD who subsequently developed IBS were more likely to experience gastrointestinal symptoms than those without IBS (p < 0.0001). Patients with concomitant IBD and IBS were more likely to develop IBD-related complications, including perforation of the intestine, gastrointestinal bleeding, colon cancer, and abdominal abscess (p < 0.05). Patients with concomitant IBD and IBS were more likely to undergo surgical interventions than patients without IBS, including colectomy, appendectomy, cholecystectomy, exploratory laparotomy, and hysterectomy (p < 0.05). Conclusions: IBS appears to be an independent risk factor for patients with IBD to develop IBD-related complications and undergo surgical interventions. Patients with concomitant IBD and IBS could represent a unique subgroup of IBD patients with more severe symptoms, highlighting the importance of accurate diagnosis and management in this population. Full article

Background: Numerous studies have investigated the applicability of Pont’s index using a variety of selection criteria. The morphology of teeth and the shapes of the face are significantly influenced by racial, cultural, and environmental factors, so the current study focused on these demographics. Methods: This study is a retrospective study and included one hundred intraoral scanned images selected from patients seeking orthodontic treatment. Medit design software was used to obtain the real measurements and compare them to the predicted values from Pont’s index. Paired t tests were used to test the validity of Pont’s index, and regression equations were advocated to predict the inter-molar, inter-premolar, and anterior arch widths via SPSS version 25. Results: There were significant differences between the real anterior, inter-premolar, and inter-molar widths and the predicted values obtained from Pont’s index, and there were weak positive correlations between the real values and the predicted values from Pont’s index. Conclusions: Pont’s index is not reliable to predict the arch widths for the Kurdish population, and new formulas are advocated. Hence, space analysis, malocclusion treatment, and arch expansion therapy should all take into account these results. Therefore, the derived equations may have further positive effects on diagnoses and treatment preparation. Full article

White blood cells (WBCs) are one of the main components of blood produced by the bone marrow. WBCs are part of the immune system that protects the body from infectious diseases and an increase or decrease in the amount of any type that causes a particular disease. Thus, recognizing the WBC types is essential for diagnosing the patient’s health and identifying the disease. Analyzing blood samples to determine the amount and WBC types requires experienced doctors. Artificial intelligence techniques were applied to analyze blood samples and classify their types to help doctors distinguish between types of infectious diseases due to increased or decreased WBC amounts. This study developed strategies for analyzing blood slide images to classify WBC types. The first strategy is to classify WBC types by the SVM-CNN technique. The second strategy for classifying WBC types is by SVM based on hybrid CNN features, which are called VGG19-ResNet101-SVM, ResNet101-MobileNet-SVM, and VGG19-ResNet101-MobileNet-SVM techniques. The third strategy for classifying WBC types by FFNN is based on a hybrid model of CNN and handcrafted features. With MobileNet and handcrafted features, FFNN achieved an AUC of 99.43%, accuracy of 99.80%, precision of 99.75%, specificity of 99.75%, and sensitivity of 99.68%. Full article