Diagnostics, Volume 11, Issue 7 (July 2021) – 172 articles

Objective: To identify dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters predictive of early disease progression in patients with metastatic renal cell cancer (mRCC) treated with anti-angiogenic tyrosine kinase inhibitors (TKI). Methods: The study was linked to a phase II/III randomised control trial. Patients underwent DCE-MRI before, at 4- and 10-weeks after initiation of TKI. DCE-MRI parameters at each time-point were derived from a single-compartment tracer kinetic model, following semi-automated tumour segmentation by two independent readers. Primary endpoint was correlation of DCE-MRI parameters with disease progression at 6-months. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) values were calculated for parameters associated with disease progression at 6 months. Inter-observer agreement was assessed using the intraclass correlation coefficient (ICC). Results: 23 tumours in 14 patients were measurable. Three patients had disease progression at 6 months. The percentage (%) change in perfused tumour volume between baseline and 4-week DCE-MRI (p = 0.016), mean transfer constant K^trans change (p = 0.038), and % change in extracellular volume (p = 0.009) between 4- and 10-week MRI, correlated with early disease progression (AUC 0.879 for each parameter). Inter-observer agreement was excellent for perfused tumour volume, K^trans and extracellular volume (ICC: 0.928, 0.949, 0.910 respectively). Conclusions: Early measurement of DCE-MRI biomarkers of tumour perfusion at 4- and 10-weeks predicts disease progression at 6-months following TKI therapy in mRCC. Full article

Primary ciliary dyskinesia (PCD) is a rare disease resulting from a defect in ciliary function that generates, among other issues, chronic upper and lower respiratory tract infections. European guidelines recommend studying ciliary function (pattern (CBP) and frequency (CBF)), together with characteristic clinical symptoms, as one of the definitive tests. However, there is no “gold standard”. The present study aims to use high-speed video microscopy to describe how CBF and CBP alter over time and at different temperatures to reduce the error rate in the diagnosis of PCD. Samples of nasal epithelium from 27 healthy volunteers were studied to assess CBF and CBP at 0, 3, 24, 48, and 72 h, at room temperature and 4 °C. It was observed that CBF increased while CBP became dyskinetic, both at room temperature and at 4 °C, as time passed, especially after 3 h. In order to preserve all ciliary function parameters and to perform a reliable analysis to improve the diagnostic process of PCD, analysis should be performed within the first 3 h of sample collection, preferably in reference centers. Full article

Far too often, one meets patients who went for years or even decades from doctor to doctor without obtaining a valid diagnosis. This brings pain to millions of patients and their families, not to speak of the enormous costs. Often patients cannot tell precisely enough which factors (or combinations thereof) trigger their problems. If conventional methods fail, we propose the use of statistics and algebra to provide doctors much more useful inputs from patients. We use statistical regression for triggering factors of medical problems, and in particular, “balanced incomplete block designs” for factors detection. These methods can supply doctors with much more valuable inputs and can also find combinations of multiple factors through very few tests. In order to show that these methods do work, we briefly describe a case in which these methods helped to solve a 60-year-old problem in a patient and provide some more examples where these methods might be particularly useful. As a conclusion, while regression is used in clinical medicine, it seems to be widely unknown in diagnosing. Statistics and algebra can save the health systems much money, as well as the patients a lot of pain. Full article

The present work aims to identify the predictors of hemodynamic failure (HF) developed during pediatric intensive care unit (PICU) stay testing a set of machine learning techniques (MLTs), comparing their ability to predict the outcome of interest. The study involved patients admitted to PICUs between 2010 and 2020. Data were extracted from the Italian Network of Pediatric Intensive Care Units (TIPNet) registry. The algorithms considered were generalized linear model (GLM), recursive partition tree (RPART), random forest (RF), neural networks models, and extreme gradient boosting (XGB). Since the outcome is rare, upsampling and downsampling algorithms have been applied for imbalance control. For each approach, the main performance measures were reported. Among an overall sample of 29,494 subjects, only 399 developed HF during the PICU stay. The median age was about two years, and the male gender was the most prevalent. The XGB algorithm outperformed other MLTs in predicting HF development, with a median ROC measure of 0.780 (IQR 0.770–0.793). PIM 3, age, and base excess were found to be the strongest predictors of outcome. The present work provides insights for the prediction of HF development during PICU stay using machine-learning algorithms. Full article

Since chronic inflammation is associated with ovarian cancer growth and progression, some clinical studies have assessed the association between the pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the prognosis of ovarian cancer. The purpose of this study was to assess the dynamic behavior of the NLR during the course of neoadjuvant chemotherapy (NACT) in patients with high grade serous (HGS) advanced epithelial ovarian cancer and assess its correlation with clinical response, progression free survival (PFS) and changes in other inflammatory indexes. We performed a prospective observational study on 161 patients who underwent NACT at the Department of Gynecologic Oncology, ARNAS G. Brotzu, Cagliari, between 2009 and 2019. NLR was evaluated before starting and after three cycles of NACT. Based on response after three cycles of NACT, patients were divided into two groups: responsive and non-responsive. The primary endpoint was to assess the predictive role of NLR by comparing the responsive and non-responsive patients at baseline and after three cycles of NACT. Secondary endpoints were (a) to correlate NLR with other inflammation markers (CRP, fibrinogen, ferritin, IL-6), albumin, and modified Glasgow Prognostic Score (mGPS) with NLR at baseline and after NACT; (b) to assess the association between NLR and PFS. We found that the NLR value at baseline was not associated with response to NACT, while a decrease in NLR after three cycles was correlated with a better response to NACT. Also, values of CRP, IL-6, ferritin, and mGPS after three cycles of NACT (but not at baseline) were significantly associated with clinical response. Moreover, we found that patients with a low NLR value after 3 cycles of NACT, but not at baseline, had a significantly higher PFS than patients with high NLR after 3 cycles of NACT. In conclusion, NLR change during treatment could serve as a predictive marker of response to NACT in patients with HGS advanced ovarian cancer. This allows for the early identification of non-responsive patients who will need treatment remodeling. Full article

Pulmonary hypertension is a rare condition that impairs patients’ quality of life and life expectancy. The development of noninvasive instruments may help elucidate the prognosis of this cardiorespiratory disease. We aimed to evaluate the utility of routinely performed noninvasive test results as prognostic markers in patients with pulmonary hypertension. We enrolled 198 patients with mean pulmonary artery pressure >25 mmHg measured at cardiac catheterisation or echocardiographic pulmonary artery systolic pressure > 40 mmHg and tricuspid regurgitation Vmax >2.9 m/s, and clinical information regarding management and follow-up studies from the date of diagnosis. Multivariate analysis revealed that female sex [HR: 0.21, (95% CI: 0.07–0.64); p = 0.006], the presence of collagenopathies [HR: 8.63, (95% CI: 2.38–31.32); p = 0.001], an increased red blood cell distribution width [HR: 1.25, (95% CI: 1.04–1.49); p = 0.017] and an increased electrocardiographic P axis (P°)/T axis (T°) ratio [HR: 0.93, (95% CI: 0.88–0.98); p = 0.009] were severity-associated factors, while older age [HR: 1.57, (95% CI: 1.04–1.28); p = 0.006], an increased QRS axis (QRS°)/T° ratio [HR: 1.21, (95% CI: 1.09–1.34); p < 0.001], forced expiratory volume in 1 s [HR: 0.94, (95% CI: 0.91–0.98); p = 0.01] and haematocrit [HR: 0.93, (95% CI: 0.87–0.99); p = 0.04] were mortality-associated factors. Our results support the importance of red blood cell distribution width, electrocardiographic ratios and collagenopathies for assessing pulmonary hypertension prognosis. Full article

Background: Central necrosis can be detected on [¹⁸F]FDG PET/CT as a region with little to no tracer uptake. Currently, there is no consensus regarding the inclusion of regions of central necrosis during volume of interest (VOI) delineation for radiomic analysis. The aim of this study was to assess how central necrosis affects radiomic analysis in PET. Methods: Forty-three patients, either with non-small cell lung carcinomas (NSCLC, n = 12) or with pheochromocytomas or paragangliomas (PPGL, n = 31), were included retrospectively. VOIs were delineated with and without central necrosis. From all VOIs, 105 radiomic features were extracted. Differences in radiomic features between delineation methods were assessed using a paired t-test with Benjamini–Hochberg multiple testing correction. In the PPGL cohort, performances of the radiomic models to predict the noradrenergic biochemical profile were assessed by comparing the areas under the receiver operating characteristic curve (AUC) for both delineation methods. Results: At least 65% of the features showed significant differences between VOI_vital-tumour and VOI_gross-tumour (65%, 79% and 82% for the NSCLC, PPGL and combined cohort, respectively). The AUCs of the radiomic models were not significantly different between delineation methods. Conclusion: In both tumour types, almost two-third of the features were affected, demonstrating that the impact of whether or not to include central necrosis in the VOI on the radiomic feature values is significant. Nevertheless, predictive performances of both delineation methods were comparable. We recommend that radiomic studies should report whether or not central necrosis was included during delineation. Full article

Tumor blood flow (TBF) is related to drug delivery and hypoxia, both of which can impact the efficacy of anti-cancer therapies. Although integrin α_vβ₃ expression is related to tumor angiogenesis, it remains unclear whether the degree of angiogenesis affects TBF. This study aimed to evaluate the expression of integrin α_vβ₃ in mouse tumor models using [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide positron emission tomography (PET) and immunohistochemical staining. PET studies were conducted using mouse C6 glioma models and MIA PaCa-2 (n = 6 each). The [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide was injected via the tail vein (2.17 ± 0.28 MBq), and 10 min static PET scans were performed. Immunohistochemical analysis was conducted using an integrin α_Vβ₃ antibody. [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide PET revealed higher uptake of the radiotracer in C6 gliomas than in MIA PaCa-2 tumors. The mean standardized uptake value was significantly higher in C6 gliomas (0.35 ± 0.058) than in MIA PaCa-2 tumors (0.17 ± 0.045). Histological analysis revealed intense integrin α_Vβ₃ expression in the C6 gliomas, whereas the MIA PaCa-2 tumors had low expression levels. This study showed that the expression of integrin α_vβ₃ can be differentiated by the [⁶⁸Ga]Ga-DOTA-c(RGDfK) peptide, suggesting the potential applicability of this peptide in the evaluation of the relationship between angiogenesis and TBF. Full article

In this short communication, we provide information on the use of the hierarchical cluster analysis of synchrotron ATR-FTIR 2D chemical imaging spectral data as a useful and powerful approach to the microspectroscopic diagnostics of molecular composition in the hybrid sound dentin/dental composite interfaces and materials, including ones developed with the use of biomimetic strategies. The described diagnostic approach can be successfully transferred to the analysis and visualisation of 2D spectral data, collected using laboratory Raman and FTIR microspectroscopy techniques. Full article

Purpose: To evaluate the value of CEUS in differentiating malignant from benign pleural effusions (PEs). Methods: From 2008 to 2017, 83 patients with PEs of unknown cause were examined using B-mode thoracic ultrasound (B-TUS), CEUS, and cytological examination. The extent of enhancement of the pleural thickening, the presence of enhancement of septa or a solid mass within the PE, and the homogeneity of the enhancement in the associated lung consolidation, were examined. Subsequently, the diagnostic value of cytology, B-TUS, and CEUS in differentiating malignant from benign PEs was determined. Results: With CEUS, markedly enhanced pleural thickening and inhomogeneous enhanced lung consolidation were significantly more frequently associated with malignancy (p < 0.05). In the subgroup analysis, the use of CEUS increased the sensitivity from 69.2 to 92.3 in patients with initial negative cytology but clinical suspicion of malignant PE; it also increased the specificity from 63.0 to 90.0, the positive predictive value from 69.2 to 92.3, the negative predictive value from 63.0 to 90.0, and the diagnostic accuracy from 66.7 to 87.5, in the evaluation of PE malignancy. Conclusion: The use of clinically based B-TUS and CEUS as a complementary method to cytological evaluation may be beneficial for evaluating a PE of unknown cause. CEUS patterns of enhanced pleural thickening and inhomogeneous enhanced lung consolidation may suggest a malignant PE. Full article

(1) Background: The early detection of sepsis is still challenging, and there is an urgent need for biomarkers that could identify patients at a high risk of developing it. We recently developed an index, namely the Sepsis Index (SI), based on the combination of two CBC parameters: monocyte distribution width (MDW) and mean monocyte volume (MMV). In this study, we sought to independently validate the performance of SI as a tool for the early detection of patients at a high risk of sepsis in the Emergency Department (ED). (2) Methods: We enrolled all consecutive patients attending the ED with a request of the CBC. MDW and MMV were measured on samples collected in K3-EDTA tubes on the UniCel DxH 900 haematology analyser. SI was calculated based on the MDW and MMV. (3) Results: We enrolled a total of 703 patients stratified into four subgroups according to the Sepsis-2 criteria: control (498), infection (105), SIRS (52) and sepsis (48). The sepsis subgroup displayed the highest MDW (median 27.5, IQR 24.6–32.9) and SI (median 1.15, IQR 1.05–1.29) values. The ROC curve analysis for the prediction of sepsis showed a good and comparable diagnostic accuracy of the MDW and SI. However, the SI displayed an increased specificity, positive predictive value and positive likelihood ratio in comparison to MDW alone. (4) Conclusions: SI improves the diagnostic accuracy of MDW for sepsis screening. Full article

The appraisal of HLA-A29 birdshot retinochoroiditis (BRC) was fraught with pitfalls and misunderstandings. Progress in investigational methods has led to better knowledge and management of the disease. Our aim was to assess some of the steps that have led to better characterisation of the clinical entity of BRC. We performed a literature search analysing the relevant progress in disease origin, investigational and imaging methods, clinicopathology and classification, diagnostic criteria and management. Following developments were judged essential in the better appraisal and understanding of the disease: (1) new immunopathological hypotheses regarding the role of endoplasmic reticulum peptidases, (2) the essential importance of HLA testing, (3) relevant imaging modalities among which indocyanine green angiography is crucial, (4) diagnostic criteria that allow early diagnosis and (5) need of an early prolonged, as well as aggressive treatment combining more than one immunosuppressive agent. Based on these findings it is now possible to better define BRC, an indolent however severe disease, unlike thought before, involving the choroidal stroma and the retina independently and concomitantly that can be diagnosed early thanks to indocyanine green angiography and should be treated early and relentlessly. Full article

The COVID-19 pandemic puts significant stress on the viral testing capabilities of many countries. Rapid point-of-care (PoC) antigen tests are valuable tools but implementing frequent large scale testing is costly. We have developed an inexpensive device for pooling swabs, extracting specimens, and detecting viral antigens with a commercial lateral flow test for the nucleocapsid protein of SARS-CoV-2 as antigen. The holder of the device can be produced locally through 3D printing. The extraction and the elution can be performed with the entire set-up encapsulated in a transparent bag, minimizing the risk of infection for the operator. With 0.35 mL extraction buffer and six swabs, including a positive control swab, 43 ± 6% (n = 8) of the signal for an individual extraction of a positive control standard was obtained. Image analysis still showed a signal-to-noise ratio of approximately 2:1 at 32-fold dilution of the extract from a single positive control swab. The relative signal from the test line versus the control line was found to scale linearly upon dilution (R² = 0.98), indicating that other pooling regimes are conceivable. A pilot project involving 14 participants and 18 pooled tests in a laboratory course at our university did not give any false positives, and an individual case study confirmed the ability to detect a SARS-CoV-2 infection with five-fold or six-fold pooling, including one swab from a PCR-confirmed COVID patient. These findings suggest that pooling can make frequent testing more affordable for schools, universities, and similar institutions, without decreasing sensitivity to an unacceptable level. Full article

Background: There is insufficient information in the literature on the comparative efficacy and tolerability of methotrexate (MTX) and methylprednisolone (MP) in patients with pulmonary sarcoidosis in assessing primary outcomes and the relapse rate. Purpose: The aim of our study was to evaluate primary and long-term outcomes of using MTX and MP in patients with pulmonary sarcoidosis. Methods: A total of 143 patients with newly diagnosed pulmonary sarcoidosis, verified by high-resolution computed tomography (CT) data, were examined. Corticosteroid (CS) therapy was used in 97 patients using MP at a dose of 0.4 mg/kg body weight for 4 weeks, followed by a dose reduction to 0.1 mg/kg by the end of the sixth month. The total duration of CS therapy was 12 months on average. Forty-six patients were treated with MTX at a dose of 10 mg/week (28) and 15 mg/week (18) per os for 6 to 12 months. The study of the relapse rate was conducted within 12 months after the CT data normalization in 60 patients after CS therapy and in 24 after MTX treatment. Results: MP treatment was successfully completed in 68 (70.1%), and MTX in 29 (60.4%) patients. In five MP patients (5.2%) and in five (10.9%) MTX, treatment was discontinued due to serious side effects. In seven (7.2%) MP patients and ten (21.7%) MTX patients, treatment required additional therapy due to the lack of efficacy. Progression with MP treatment (17–17.5%) was more common than with MTX (2–4.3%; Chi square = 4.703, p = 0.031). Relapses after MP therapy were observed in 26 (43.3%) patients, and after MTX therapy in 2 (8.3%; Chi square = 9.450, p = 0.003). Conclusion: In patients with pulmonary sarcoidosis, MTX monotherapy does not differ significantly from MP monotherapy in terms of the level of efficacy and the rate of serious side effects. Increasing the MTX dose from 10 to 15 mg/week accelerates the rate of regression of sarcoidosis, improves treatment efficacy, and does not affect the rate of serious side effects. When using MTX, there is a significant decrease in the incidence of treatment resistance and the relapse rate. Full article

Atrial fibrillation (AF) is an important arrhythmia in hypertrophic cardiomyopathy (HCM). We aimed to explore whether a complex evaluation of the left ventricle (LV) using modern echocardiography techniques, additionally to the left atrium (LA) boosts the probability of AF diagnosis. Standard echocardiography, 2D and 3D speckle tracking, were performed for LA and LV evaluation in HCM patients and healthy volunteers. Of 128 initially qualified HCM patients, 60 fulfilled included criteria, from which 43 had a history of AF, and 17 were without AF. LA volume index and peak strain, LV ejection fraction, and strains were significant predictors of AF. In addition, 2D global longitudinal strain (GLS) for LV at cut off −16% turned out to be the most accurate predictor of AF (OR 48.00 [95% CI 2.68–859.36], p = 0.001), whereas the combination of LA peak strain ≤ 22% and LV GLS ≥ −16% had the highest discriminatory power (OR 76.36 [95% CI 4.13–1411.36], p = 0.001). AF in HCM patients seems to be LA as well as LV disease. Revealing lower strain for LV, in addition to lower LA strain, may have an important impact on accurate characteristics of HCM patients with AF history. Full article

Oral cancer is one of the most common head and neck malignancies and has an overall 5-year survival rate that remains below 50%. Oral cancer is generally preceded by oral potentially malignant disorders (OPMDs) but determining the risk of OPMD progressing to cancer remains a difficult task. Several diagnostic technologies have been developed to facilitate the detection of OPMD and oral cancer, and some of these have been translated into regulatory-approved in vitro diagnostic systems or medical devices. Furthermore, the rapid development of novel biomarkers, electronic systems, and artificial intelligence may help to develop a new era where OPMD and oral cancer are detected at an early stage. To date, a visual oral examination remains the routine first-line method of identifying oral lesions; however, this method has certain limitations and as a result, patients are either diagnosed when their cancer reaches a severe stage or a high-risk patient with OPMD is misdiagnosed and left untreated. The purpose of this article is to review the currently available diagnostic methods for oral cancer as well as possible future applications of novel promising technologies to oral cancer diagnosis. This will potentially increase diagnostic options and improve our ability to effectively diagnose and treat oral cancerous-related lesions. Full article

Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis is challenging. We evaluated the influence of pre-procedural imaging and cystic duct cholangiography on ETGBD. Patients who underwent ETGBD for acute cholecystitis were retrospectively examined. The rate of gallbladder contrast on cholangiography, the accuracy of cystic duct direction and location by computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), and the relationship between pre-procedural imaging and the technical success of ETGBD were investigated. A total of 145 patients were enrolled in this study. Gallbladder contrast on cholangiography was observed in 29 patients. The accuracy of cystic duct direction and location (proximal or distal, right or left, and cranial or caudal) by CT were, respectively, 79%, 60%, and 58% by CT and 68%, 55%, and 58% by MRCP. Patients showing gallbladder contrast on cholangiography underwent ETGBD with a significantly shorter procedure time and a lower rate of cystic duct injury. No other factors affecting procedure time, technical success, and cystic duct injury were identified. Pre-procedural evaluation of cystic duct direction and location by CT or MRCP was difficult in patients with acute cholecystitis. Patients who showed gallbladder contrast on cholangiography showed a shorter procedure time and a lower rate of cystic duct injury. Full article

The detection and monitoring of biomarkers in body fluids has been used to improve human healthcare activities for decades. In recent years, researchers have focused their attention on applying the point-of-care (POC) strategies into biomarker detection. The evolution of mobile technologies has allowed researchers to develop numerous portable medical devices that aim to deliver comparable results to clinical measurements. Among these, optical-based detection methods have been considered as one of the common and efficient ways to detect and monitor the presence of biomarkers in bodily fluids, and emerging aggregation-induced emission luminogens (AIEgens) with their distinct features are merging with portable medical devices. In this review, the detection methodologies that use optical measurements in the POC systems for the detection and monitoring of biomarkers in bodily fluids are compared, including colorimetry, fluorescence and chemiluminescence measurements. The current portable technologies, with or without the use of smartphones in device development, that are combined with optical biosensors for the detection and monitoring of biomarkers in body fluids, are also investigated. The review also discusses novel AIEgens used in the portable systems for the detection and monitoring of biomarkers in body fluid. Finally, the potential of future developments and the use of optical detection-based portable devices in healthcare activities are explored. Full article

Today, there are many parameters used for cardiovascular risk quantification and to identify many of the high-risk subjects; however, many of them do not reflect reality. Modern personalized medicine is the key to fast and effective diagnostics and treatment of cardiovascular diseases. One step towards this goal is a better understanding of connections between numerous risk factors. We used Factor analysis to identify a suitable number of factors on observed data about patients hospitalized in the East Slovak Institute of Cardiovascular Diseases in Košice. The data describes 808 participants cross-identifying symptomatic and coronarography resulting characteristics. We created several clusters of factors. The most significant cluster of factors identified six factors: basic characteristics of the patient; renal parameters and fibrinogen; family predisposition to CVD; personal history of CVD; lifestyle of the patient; and echo and ECG examination results. The factor analysis results confirmed the known findings and recommendations related to CVD. The derivation of new facts concerning the risk factors of CVD will be of interest to further research, focusing, among other things, on explanatory methods. Full article

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is an environment that provides various biological niches, such as the teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome also plays an important role in the triggering, development, and progression of oral and systemic diseases. In recent years, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology and is overwhelmingly promising compared to the previous era. It has been found that patients with oral and systemic diseases have variations in their oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that the oral microbiome plays in influencing oral and systemic diseases and furthers the knowledge related to the oral microbiome produced over the past 30 years. A wide range of updates were provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and can help to develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics. Full article

Purpose: In recent years, cardiac magnetic resonance (CMR) has been used to assess LV diastolic function. In this systematic review, studies were identified where CMR parameters had been evaluated in healthy and/or patient groups with proven diastolic dysfunction or known to develop heart failure with preserved ejection fraction. We aimed at describing the parameters most often used, thresholds where possible, and correlation to echocardiographic and invasive measurements. Methods and results: A systematic literature review was performed using the databases of PubMed, Embase, and Cochrane. In total, 3808 articles were screened, and 102 studies were included. Four main CMR techniques were identified: tagging; time/volume curves; mitral inflow quantification with velocity-encoded phase-contrast sequences; and feature tracking. Techniques were described and estimates were presented in tables. From published studies, peak change of torsion shear angle versus volume changes in early diastole (−dφ′/dV′) (from tagging analysis), early peak filling rate indexed to LV end-diastolic volume <2.1 s⁻¹ (from LV time-volume curve analysis), enlarged LA maximal volume >52 mL/m², lowered LA total (<40%), and lowered LA passive emptying fractions (<16%) seem to be reliable measures of LV diastolic dysfunction. Feature tracking, especially of the atrium, shows promise but is still a novel technique. Conclusion: CMR techniques of LV untwisting and early filling and LA measures of poor emptying are promising for the diagnosis of LV filling impairment, but further research in long-term follow-up studies is needed to assess the ability for the parameters to predict patient related outcomes. Full article

Background: Malignant mesothelioma (MM) is an aggressive and incurable carcinoma that is primarily caused by asbestos exposure. However, the current diagnostic tool for MM is still under-developed. Therefore, the aim of this study is to explore the diagnostic significance of a strategy that combined plasma-based metabolomics with machine learning algorithms for MM. Methods: Plasma samples collected from 25 MM patients and 32 healthy controls (HCs) were randomly divided into train set and test set, after which analyzation was performed by liquid chromatography-mass spectrometry-based metabolomics. Differential metabolites were screened out from the samples of the train set. Subsequently, metabolite-based diagnostic models, including receiver operating characteristic (ROC) curves and Random Forest model (RF), were established, and their prediction accuracies were calculated for the test set samples. Results: Twenty differential plasma metabolites were annotated in the train set; 10 of these metabolites were validated in the test set. The seven most prevalent diagnostic metabolites were taurocholic acid), 0.7142 (uracil), 0.7142 (biliverdin), 0.8571 (histidine), 0.5000 (tauroursodeoxycholic acid), 0.8571 (pyrroline hydroxycarboxylic acid), and 0.7857 (phenylalanine). Furthermore, RF based on 20 annotated metabolites showed a prediction accuracy of 0.9286, and its optimized version achieved 1.0000 in the test set. Moreover, the comparison between the samples of peritoneal MM (n = 8) and pleural MM (n = 17) illustrated a significant increase in levels of taurocholic acid and tauroursodeoxycholic acid, as well as an evident decrease in biliverdin. Conclusions: Our results revealed the potential diagnostic value of plasma-based metabolomics combined with machine learning for MM. Further research with large sample size is worthy conducting. Moreover, our data demonstrated dysregulated metabolism pathways in MM, which aids in better understanding of molecular mechanisms related to the initiation and development of MM. Full article

There has been no machine learning study with a rich collection of clinical, sonographic markers to compare the performance measures for a variety of newborns’ weight-for-height indicators. This study compared the performance measures for a variety of newborns’ weight-for-height indicators based on machine learning, ultrasonographic data and maternal/delivery information. The source of data for this study was a multi-center retrospective study with 2949 mother–newborn pairs. The mean-squared-error-over-variance measures of five machine learning approaches were compared for newborn’s weight, newborn’s weight/height, newborn’s weight/height² and newborn’s weight/hieght³. Random forest variable importance, the influence of a variable over average node impurity, was used to identify major predictors of these newborns’ weight-for-height indicators among ultrasonographic data and maternal/delivery information. Regarding ultrasonographic fetal biometry, newborn’s weight, newborn’s weight/height and newborn’s weight/height² were better indicators with smaller mean-squared-error-over-variance measures than newborn’s weight/height³. Based on random forest variable importance, the top six predictors of newborn’s weight were the same as those of newborn’s weight/height and those of newborn’s weight/height²: gestational age at delivery time, the first estimated fetal weight and abdominal circumference in week 36 or later, maternal weight and body mass index at delivery time, and the first biparietal diameter in week 36 or later. These six predictors also ranked within the top seven for large-for-gestational-age and the top eight for small-for-gestational-age. In conclusion, newborn’s weight, newborn’s weight/height and newborn’s weight/height² are more suitable for ultrasonographic fetal biometry with smaller mean-squared-error-over-variance measures than newborn’s weight/height³. Machine learning with ultrasonographic data would be an effective noninvasive approach for predicting newborn’s weight, weight/height and weight/height². Full article

Hereditary hemochromatosis (HH) is a genetic disease leading to excessive iron absorption, its accumulation, and oxidative stress induction causing different organ damage, including the heart. The process of cardiac involvement is slow and lasts for years. Cardiac pathology manifests as an impaired diastolic function and cardiac hypertrophy at first and as dilatative cardiomyopathy and heart failure with time. From the moment of heart failure appearance, the prognosis is poor. Therefore, it is crucial to prevent those lesions by upfront therapy at the preclinical phase of the disease. The most useful diagnostic tool for detecting cardiac involvement is echocardiography. However, during an early phase of the disease, when patients do not present severe abnormalities in serum iron parameters and severe symptoms of other organ involvement, heart damage may be overlooked due to the lack of evident signs of cardiac dysfunction. Considerable advancement in echocardiography, with particular attention to speckle tracking echocardiography, allows detecting discrete myocardial abnormalities and planning strategy for further clinical management before the occurrence of substantial heart damage. The review aims to present the current state of knowledge concerning cardiac involvement in HH. In addition, it could help cardiologists and other physicians in their everyday practice with HH patients. Full article

Primary Ciliary Dyskinesia (PCD) is a rare, under-recognized disease that affects respiratory ciliary function, resulting in chronic oto-sino-pulmonary disease. The PCD clinical phenotype overlaps with other common respiratory conditions and no single diagnostic test detects all forms of PCD. In 2018, PCD experts collaborated with the American Thoracic Society (ATS) to create a clinical diagnostic guideline for patients across North America, specifically considering the local resources and limitations for PCD diagnosis in the United States and Canada. Nasal nitric oxide (nNO) testing is recommended for first-line testing in patients ≥5 years old with a compatible clinical phenotype; however, all low nNO values require confirmation with genetic testing or ciliary electron micrograph (EM) analysis. Furthermore, these guidelines recognize that not all North American patients have access to nNO testing and isolated genetic testing is appropriate in cases with strong clinical PCD phenotypes. For unresolved diagnostic cases, referral to a PCD Foundation accredited center is recommended. The purpose of this narrative review is to provide insight on the North American PCD diagnostic process, to enhance the understanding of and adherence to current guidelines, and to promote collaboration with diagnostic pathways used outside of North America. Full article

Celiac disease (CD) is diagnosed by a combination of specific serology and typical duodenal lesions. The histological confirmation of CD, mandatory in the majority of patients with suspected CD, is based on invasive and poorly tolerated procedures, such as upper gastrointestinal endoscopy. In this study we propose an alternative and non-invasive methodology able to confirm the diagnosis of CD based on the analysis of serum samples using the Raman spectroscopy technique. Three different bands centered at 1650, 1450 and 1003 cm⁻¹ have been considered and the A₁₄₅₀/A₁₀₀₃ and A₁₆₅₀/A₁₀₀₃ ratios have been computed to discriminate between CD and non-CD subjects. The reliability of the methodology was validated by statistical analysis using receiver operating characteristic (ROC) curves. The Youden index was also determined to obtain optimal cut-off points. The obtained results highlighted that the proposed methodology was able to distinguish between CD and non-CD subjects with 98% accuracy. The optimal cut-off points revealed, for both the A₁₄₅₀/A₁₀₀₃ and A₁₆₅₀/A₁₀₀₃ ratios, high values of sensitivity and specificity (>95.0% and >92.0% respectively), confirming that Raman spectroscopy may be considered a valid alternative to duodenal biopsy and demonstrates spectral changes in the secondary structures of the protein network. Full article

Extracellular vesicles (EVs) are secreted by various cells in the body fluid system and have been found to influence vessel formation and inflammatory responses in a variety of diseases. However, which EVs and their subtypes are involved in vascular retinal diseases is still unclear. Therefore, the aim of this study was to explore the particle distribution of EVs in retinal neovascular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, and central retinal vein occlusion. The aqueous humor was harvested from 20 patients with different retinal neovascular diseases and six patients with cataracts as the control group. The particle distribution was analyzed using nanoparticle tracking analysis (NTA) and transmitting electron microscopy (TEM). The results revealed that the disease groups had large amounts of EVs and their subtypes compared to the control group. After isolating exosomes, a higher expression of CD81⁺ exosomes was shown in the disease groups using flow cytometry. The exosomes were then further classified into three subtypes of exomeres, small exosomes, and large exosomes, and their amounts were shown to differ depending on the disease type. To the best of our knowledge, this is the first study to elucidate the dynamics of EVs in retinal neovascular diseases using clinical cases. Our findings demonstrated the possible functionality of microvesicles and exosomes, indicating the potential of exosomes in the diagnosis and therapy of retinal neovascular diseases. Full article

Biomarkers play a vital role in clinical care. They enable early diagnosis and treatment by identifying a patient’s condition and disease course and act as an outcome measure that accurately evaluates the efficacy of a new treatment or drug. Due to the rapid development of digital technologies, digital biomarkers are expected to grow tremendously. In the era of change, this scoping review was conducted to see which digital biomarkers are progressing in neuromuscular disorders, a diverse and broad-range disease group among the neurological diseases, to discover available evidence for their feasibility and reliability. Thus, a total of 10 studies were examined: 9 observational studies and 1 animal study. Of the observational studies, studies were conducted with amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), and spinal muscular atrophy (SMA) patients. Non-peer reviewed poster presentations were not considered, as the articles may lead to erroneous results. The only animal study included in the present review investigated the mice model of ALS for detecting rest disturbances using a non-invasive digital biomarker. Full article

Background: Endometrial cancer is the most common pelvic gynecological cancer in France. The most frequent symptom is post-menopausal bleeding and is one of the primary reasons for consultation in gynecological emergencies. The treatment is very codified and consists of a surgical intervention for anatomopathological analysis. The latter is frequently reassuring. These interventions are often performed in mild situations and there is currently no element to be sufficiently reassuring to avoid surgery. This study aims to explore the sensitivity of an innovative marker: Human Epididymis 4 (HE4) in the diagnosis approach of endometrial cancer in case of postmenopausal bleedings. Methods: This is a prospective multicenter diagnostic study with three centers involved. Inclusion criteria are any patient with post-menopausal bleeding who is to undergo hysteroscopy, endometrial biopsy, or endometrial resection. In accordance with the recommendations for the management of post-menopausal bleedings, the medical conduct consists of performing a clinical examination, an ultrasound and, in general, even in case of paraclinical examination reassuring, an anatomopathological analysis. This pathological analysis can be obtained in several ways: biopsy, hysteroscopy-curettage (which is the most frequently performed surgery), and hysterectomy. Our protocol consists of taking a blood sample from each woman who will undergo one of the interventions mentioned above. The dosage of HE4 and CA125 requires the withdrawal of an additional heparinized tube during the preoperative assessment usually performed. This research is therefore classified as non-interventional. The primary outcome is to evaluate the sensitivity of the HE4 marker in patients with postmenopausal bleeding in the diagnosis of endometrial cancer. The secondary outcomes are other parameters (specificity, VPP, VPN) of HE4, Evaluating the diagnostic capabilities of the CA125 marker alone and associated with HE4, as well as those of the REM and REM-B algorithms. We aim to include 100 patients over a period of one year in three centers. Discussion: As of now, there is no biological marker used in routine practice in the diagnosis of endometrial cancer. The ultimate goal of HE4 in endometrial cancer is to avoid surgery for those who are identified as non-sick. This study is the precursor of others for use in routine practice, HE4 would represent a great help to diagnosis if our study demonstrates it as reliable in the management of these patients and avoid many unnecessary and risky surgeries. Full article

Widely established compared to myocardial perfusion imaging, cardiac autonomous nervous system (CANS) assessment by radiopharmaceutical means is of potential use especially to arrhythmogenic diseases not correlated with anatomic or functional alterations revealed by classical imaging techniques. Molecular imaging of both pre- and postsynaptic functions of the autonomous nervous system is currently feasible, since single photon emission tomography (SPECT) and positron emission tomography (PET) have the ability to reveal the insights of molecular pathophysiology depicting both sympathetic and parasympathetic imbalance in discrete heart pathologies. This review provides not only a brief presentation of radiopharmaceuticals used for non-invasive CANS imaging in the case of ventricular arrhythmias, but also a current update on ventricular tachycardias, cardiomyopathies, Brugada and Long QT syndrome literature. Full article