Diagnostics, Volume 9, Issue 3 (September 2019) – 58 articles

Somatosensory evoked potentials (SSEPs) are a valuable tool to assess functional integrity of the somatosensory pathways and for the prediction of sensorimotor outcome in perinatal injuries, such as perinatal hypoxia-ischemia (HI). In the present research, we studied the translational potential of SSEPs together with sensory function in the male adult rat with perinatal HI compared to the male healthy adult rat. Both somatosensory response and evoked potential were measured at 10-11 months after global perinatal HI. Clear evoked potentials were obtained, but there were no group differences in the amplitude or latency of the evoked potentials of the preceding sensory response. The bilateral tactile stimulation test was also normal in both groups. This lack of effect may be ascribed to the late age-of-testing and functional recovery of the rats. Full article

A urinary tract infection (UTI) can be diagnosed via urinalysis, consisting of a dipstick test and manual microscopic examination. Point-of-care (POC) image-based systems have been designed to automate the microscopic examination for low-volume laboratories or low-resource clinics. In this pilot study, acridine orange (AO) was evaluated as a fluorescence-based contrast agent to aid in detecting and enumerating urine sediment specific for diagnosing a UTI. Acridine orange staining of epithelial cells, leukocytes, and bacteria provided sufficient contrast to successfully implement image segmentation techniques, which enabled the extraction of classifiable morphologic features. Surface area bounded by each cell border was used to differentiate the sediment; epithelial cells were larger than 500μm², bacteria were less than 30μm², and leukocytes in between. This image-based semi-automated technique using AO resulted in similar cell counts to the clinical results, which demonstrates the feasibility of AO as an aid for POC urinalysis systems. Full article

In-depth understanding of early cardiovascular manifestations in diabetes is high on international research and prevention agendas given that cardiovascular events are the leading cause of death for diabetic patients. Our aim was to review recent developments in the echocardiographic assessment of left ventricular diastolic dysfunction (LVDD) as a telltale pre-clinical disturbance preceding diabetic cardiomyopathy. We analyzed papers in which patients had been comprehensively assessed echocardiographically according to the latest LVDD guidelines (2016), and those affording comparisons with previous, widely used recommendations (2009). We found that the updated algorithm for LVDD is more effective in predicting adverse cardiovascular events in patients with established LVDD, and less specific in grading other patients (labelled “indeterminate”). This may prove instrumental for recruiting “indeterminate” LVDD cases among patients with type 2 diabetes mellitus (T2DM) in future screening programs. As an interesting consideration, the elevated values of the index E/e’ can point to early diastolic impairment, foretelling diabetic cardiomyopathy. Identifying subclinical signs early makes clinical sense, but the complex nature of T2DM calls for further research. Specifically, longitudinal studies on rigorously selected cohorts of diabetic patients are needed to better understand and predict the subtle, slow onset of cardiac manifestations with T2DM as a complicating backdrop. Full article

An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response. Full article

Fine needle aspiration (FNA) is considered the gold standard in the diagnostic of thyroid nodules. Using the recommended BETHESDA reporting system, up to 20% of results are classified as intermediate cytology. As there is no consensus whether ultrasound evaluation, lobectomy or surgery is the best treatment option, intermediate cytology results are considered a grey zone of the FNA. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in the process of diagnosis and evaluation of the intermediate cytology cases after FNA. We evaluated 54 consecutive cases with intermediate cytology on FNA, using conventional B-mode ultrasound (2B), and strain elastography, using a linear multifrequency 6–13 MHz linear probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All nodules were classified with our Thyroid Imaging Report and Data System (TI-RADS) proposed model, considering: vertical appearance, with antero-posterior diameter bigger than the transvers diameter, the so called taller than wide shape, irregular borders, intranodular inhomogeneity, marked hypoecogenicity, micro calcifications, the presence of suspect lymph nodes, and increased stiffness as suspicious for malignancy. The classification outcomes were compared with the pathology results, considered the gold standard diagnosis. The prevalence of cancer was 28.8%, with 13/45 cases having a clear diagnostic of cancer. Six cases were diagnosed with borderline follicular neoplasia, a category with unclear evolution, also considered as malignant in the analysis of the imaging results. In total, 16/19 cancer cases had increased stiffness on elastography. The cancer prevalence increased with TI-RADS category, being 25% in TI-RADS 4b category and 92.8% in TI-RADS 5 category. The AUROC (Area Under Receiver Operating Curve) of elastography alone, in differentiation of malignant thyroid nodules was 74.9%; the combination of elastographic and conventional ultrasound characteristics generated an even better AUROC, of 84.5%. The combined conventional ultrasound and elastography identified thyroid cancer in cases with intermediate cytology with a sensitivity of 89.5% with a specificity of 50%. High risk thyroid nodules, identified by combined high risk conventional ultrasound characteristics and increased stiffness, on strain elastography, are highly predictive for malignancy, in the intermediate cytology cases. Full article

Background. Pediatric open-heart surgery with cardiopulmonary bypass (CPB) still remains a risky interventional procedure at high mortality/morbidity. To date, there are no clinical, laboratory, and/or monitoring parameters providing useful information on perioperative stress. We therefore investigated whether blood concentrations of glutathione (GSH), a powerful endogenous antioxidant, changed in the perioperative period. Methods. We conducted an observational study in 35 congenital heart disease (CHD) children in whom perioperative standard laboratory and monitoring parameters and GSH blood levels were assessed at five monitoring time points. Results. GSH showed a pattern characterized by a progressive increase from pre-surgery up to 24 h after surgery, reaching its highest peak at the end of CPB. GSH measured at the end of CPB correlated with CPB duration, cross-clamping, arterial oxygen partial pressure, and with body core temperature. Conclusions. The increase in GSH levels in the perioperative period suggests a compensatory mechanism to oxidative damage during surgical procedure. Caution is needed in controlling different CPB phases, especially systemic reoxygenation in a population that is per se more prone to oxidative stress/damage. The findings may point the way to detecting the optimal temperature and oxygenation target by biomarker monitoring. Full article

Next Generation Sequencing (NGS) is a promising tool for the improvement of tumor molecular profiling in view of the identification of a personalized treatment in oncologic patients. To verify the potentiality of a targeted NGS (Ion AmpliSeq™ Cancer Hotspot Panel v2), selected melanoma samples (n = 21) were retrospectively analyzed on S5 platform in order to compare NGS performance with the conventional techniques adopted in our routine clinical setting (Sequenom MassARRAY system, Sanger sequencing, allele-specific real-time PCR). The capability in the identification of rare and low-frequency mutations in the main genes involved in melanoma (BRAF and NRAS genes) was verified and integrated with the results deriving from other oncogenes and tumor suppressor genes. The analytical evaluation was carried out by the analysis of DNA derived from control cell lines and FFPE (Formalin-Fixed, Paraffin-Embedded) samples to verify that the achieved resolution of uncommon mutations and low-frequency variants was suitable to meet the technical and clinical requests. Our results demonstrate that the amplicon-based NGS approach can reach the sensitivity proper of the allele-specific assays together with the high specificity of a sequencing method. An overall concordance among the tested methods was observed in the identification of classical and uncommon mutations. The assessment of the quality parameters and the comparison with the orthogonal methods suggest that the NGS method could be implemented in the clinical setting for melanoma molecular characterization. Full article

This paper summarises the current status of two novel short cognitive tests (SCT), known as Test Your Memory (TYM) and Test Your Memory for Mild Cognitive Impairment (TYM-MCI). The history of and recent research on the TYM and TYM-MCI are summarised in applications for Alzheimer’s and non-Alzheimer’s dementia and mild cognitive impairment. The TYM test can be used in a general neurology clinic and can help distinguish patients with Alzheimer’s disease (AD) from those with no neurological cause for their memory complaints. An adapted tele-TYM test administered by telephone to patients produces scores which correlate strongly with the clinic-administered Addenbrookes Cognitive Examination revised (ACE-R) test and can identify patients with dementia. Patients with AD decline on the TYM test at a rate of 3.6–4.1 points/year. Full article

There is great interest in the study of brain structural connectivity, as white matter abnormalities have been implicated in many disease states. Diffusion magnetic resonance imaging (MRI) provides a powerful means to characterise structural connectivity non-invasively, by using a fibre-tracking algorithm. The most widely used fibre-tracking strategy is based on the step-wise generation of streamlines. Despite their popularity and widespread use, there are a number of practical considerations that must be taken into account in order to increase the robustness of streamlines tracking results, particularly when these methods are used to study brain structural connectivity, and the connectome. This review article describes what we consider the ‘seven deadly sins’ of mapping structural connections using diffusion MRI streamlines fibre-tracking, with particular emphasis on ‘sins’ that can be practically avoided and they can have an important impact in the results. It is shown that there are important ‘deadly sins’ to be avoided at every step of the pipeline, such as during data acquisition, during data modelling to estimate local fibre architecture, during the fibre-tracking process itself, and during quantification of the tracking results. The recommendations here are intended to inform users on potential important shortcomings of their current tracking protocols, as well as to guide future users on some of the key issues and decisions that must be faced when designing their processing pipelines. Full article

Over the past 35 years, the proliferation of technology and the advent of the internet have resulted in many reliable and easy to administer batteries for assessing cognitive function. These approaches have great potential for affecting how the health care system monitors and screens for cognitive changes in the aging population. Here, we review these new technologies with a specific emphasis on what they offer over and above traditional ‘paper-and-pencil’ approaches to assessing cognitive function. Key advantages include fully automated administration and scoring, the interpretation of individual scores within the context of thousands of normative data points, the inclusion of ‘meaningful change’ and ‘validity’ indices based on these large norms, more efficient testing, increased sensitivity, and the possibility of characterising cognition in samples drawn from the general population that may contain hundreds of thousands of test scores. The relationship between these new computerized platforms and existing (and commonly used) paper-and-pencil tests is explored, with a particular emphasis on why computerized tests are particularly advantageous for assessing the cognitive changes associated with aging. Full article

Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of the IFN score is proposed for the screening of monogenic interferonopathies, like the Aicardi-Goutières syndrome, or to stratify subjects with systemic lupus erythematosus to receive IFN-targeted treatments. Apart from these scenarios, there is no agreement on the diagnostic value of the score in distinguishing IFN-related disorders from diseases dominated by other types of cytokines. Since the IFN score is currently measured in several research hospitals, merging experiences could help define the potential of scoring IFN inflammation in clinical practice. However, the IFN score calculated at different laboratories may be hardly comparable due to the distinct sets of IFN-stimulated genes assessed and to different controls used for data normalization. We developed a reliable approach to minimize the inter-laboratory variability, thereby providing shared strategies for the IFN signature analysis and allowing different centers to compare data and merge their experiences. Full article

The detection of carcinoma in situ (CIS) is essential for the management of high-risk non-muscle invasive bladder cancers. Here, we focused on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with photodynamic diagnosis (PDD) for the detection of CIS. A total of 45 patients undergoing pre-surgical DCE-MRI and PDD-assisted endoscopic surgery accompanied by biopsies of the eight segmentations were analyzed. Immunohistochemical analysis of the biopsies revealed hypervascularity of CIS lesions, a cause of strong submucosal contrast-enhancement. It was found that 56 (16.2%) of 344 biopsies had pathologically proven CIS. In the DCE-MRI, the overall sensitivity and specificity for detecting CIS were 48.2% and 81.9%, respectively. We set out two different combinations of PDD and DCE-MRI for detecting CIS. Combination 1 was positive when either the PDD or DCE-MRI were test-positive. Combination 2 was positive only when both PDD and DCE-MRI were test-positive. The overall sensitivity of combinations 1 and 2 were 75.0% and 37.5%, respectively (McNemar test, vs PDD alone; p = 0.041 and p < 0.001, respectively). However, the specificity was 74.0% and 91.7%, respectively (vs PDD alone; both p < 0.001). Our future goal is to establish ‘MRI-PDD fusion transurethral resction of the bladder tumor (TURBT), which could be an effective therapeutic and diagnostic approach in the clinical management of high-risk disease. Full article

Splenosis is a rare disease which typically forms single or multiple round masses. A 45-year-old male was referred for investigation of an abdominal mass. He had a history of splenic injury from a traffic accident at age 19. Contrast-enhanced computed tomography showed a well-enhanced, multi-nodular mass lesion, 3.5 cm in size, located below the stomach. An endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) for the mass was inconclusive. A surgery was performed, and pathology of the resected mass confirmed splenosis. Clinicians must bear in mind the possibility of occurrence of splenosis after splenic trauma and its image variations. Full article

Isolated tubal torsions presenting to the emergency department are a very rare cause of pediatric acute abdominal pain. Since making the diagnosis early is of importance in terms of affecting tubal damage and fertility, we aimed to evaluate cases of isolated tubal torsions in light of the literature. This study included 10 patients under 18 years of age who presented to the emergency department with abdominal pain between January 2003 and December 2018. The mean age was 14.5 ± 1.43 years (range: 12–17 years). The demographic characteristics, surgical findings and techniques, and concomitant pathology results of these patients were retrospectively evaluated. The reason for presenting to the emergency department for the 10 patients included in the study was abdominal pain. The mean duration of hospital admission with pain was 4.97 days. The onset of pain was less than 24 h in seven patients (70%) and more than 24 h in three patients (30%). Of the patients, nine (90%) had tenderness in the lower abdominal quadrant, five (5%) had defense, and three (30%) had rebound. Nausea, vomiting and leukocytosis were present in 50% of the cases. Right and left tubal involvement of the cases was equal. Seven (70%) of the isolated tubal torsions were accompanied by paraovarian cysts. Eight patients (80%) underwent open surgery and two (20%) underwent laparoscopic intervention. Detorsion was performed on five (50%) patients and salpingectomy was performed on five (50%) patients. Isolated tubal torsion should be considered in children presenting with acute abdominal pain in early adolescence. Early diagnosis is important for the preservation of fertility. Full article

Background: Ultrasound is operator-dependent, and its value and efficacy in fetal morphology assessment in a low-resource setting is poorly understood. We assessed the value and efficacy of fetal morphology ultrasound assessment in a Nigerian setting. Materials and Methods: We surveyed fetal morphology ultrasound performed across five facilities and followed-up each fetus to ascertain the outcome. Fetuses were surveyed in the second trimester (18th–22nd weeks) using the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guideline. Clinical and surgical reports were used as references to assess the diagnostic efficacy of ultrasound in livebirths, and autopsy reports to confirm anomalies in terminated pregnancies, spontaneous abortions, intrauterine fetal deaths, and still births. We calculated sensitivity, specificity, positive and negative predictive values, Area under the curve (AUC), Youden index, likelihood ratios, and post-test probabilities. Results: In total, 6520 fetuses of women aged 15–46 years (mean = 31.7 years) were surveyed. The overall sensitivity, specificity, and AUC were 77.1 (95% CI: 68–84.6), 99.5 (95% CI: 99.3–99.7), and 88.3 (95% CI: 83.7–92.2), respectively. Other performance metrics were: positive predictive value, 72.4 (95% CI: 64.7–79.0), negative predictive value, 99.6 (95% CI: 99.5–99.7), and Youden index (77.1%). Abnormality prevalence was 1.67% (95% CI: 1.37–2.01), and the positive and negative likelihood ratios were 254 (95% CI: 107.7–221.4) and 0.23 (95% CI: 0.16–0.33), respectively. The post-test probability for positive test was 72% (95% CI: 65–79). Conclusion: Fetal morphology assessment is valuable in a poor economics setting, however, the variation in the diagnostic efficacy across facilities and the limitations associated with the detection of circulatory system anomalies need to be addressed. Full article

The measurement of the liver function via the plasma disappearance rate of indocyanine green (PDR_ICG) is a sensitive bed-side tool in critical care. Yet, recent evidence has questioned the value of this method for hyperdynamic conditions. To evaluate this technique in different hemodynamic settings, we analyzed the PDR_ICG and corresponding pharmacokinetic models after endotoxemia or hemorrhagic shock in rats. Male anesthetized Sprague-Dawley rats underwent hemorrhage (mean arterial pressure 35 ± 5 mmHg, 90 min) and 2 h of reperfusion, or lipopolysaccharide (LPS) induced moderate or severe (1.0 vs. 10 mg/kg) endotoxemia for 6 h (each n = 6). Afterwards, PDR_ICG was measured, and pharmacokinetic models were analyzed using nonlinear mixed effects modeling (NONMEM^®). Hemorrhagic shock resulted in a significant decrease of PDR_ICG, compared with sham controls, and a corresponding attenuation of the calculated ICG clearance in 1- and 2-compartment models, with the same log-likelihood. The induction of severe, but not moderate endotoxemia, led to a significant reduction of PDR_ICG. The calculated ICG blood clearance was reduced in 1-compartment models for both septic conditions. 2-compartment models performed with a significantly better log likelihood, and the calculated clearance of ICG did not correspond well with PDR_ICG in both LPS groups. 3-compartment models did not improve the log likelihood in any experiment. These results demonstrate that PDR_ICG correlates well with ICG clearance in 1- and 2-compartment models after hemorrhage. In endotoxemia, best described by a 2-compartment model, PDR_ICG may not truly reflect the ICG clearance. Full article

Liver fibrosis staging is of great clinical importance because it is used to assess the severity of the underlying chronic liver disease. Among various imaging-based methods, apparent diffusion coefficient (ADC) measurement using diffusion-weighted imaging (DWI) has the potential to be used as an imaging biomarker for liver fibrosis assessment. In this study, we investigated the usefulness of liver ADC normalization using the spleen as a reference organ in liver fibrosis staging with 66 patients who underwent liver magnetic resonance imaging (MRI), transient elastography (TE), and surgical resection of a hepatic mass. ADC values of the liver (ADC_liver) and spleen were analyzed, and the spleen was used for ADC_liver normalization (nADC_liver). ADC_liver showed a weak negative correlation with TE (r = −0.246; p = 0.047) and fibrosis stage (r = −0.269; p = 0.029), while n ADC_liver showed a moderate negative correlation with TE (r = −0.504; p < 0.001) and fibrosis stage (r = −0.579; p < 0.001). AUC values for nADC_liver (0.777–0.875) were higher than those for ADC_liver for each stage of fibrosis (0.596–0.713, p = 0.037–0.157). AUC values for TE (0.726–0.884) and nADC_liver were not statistically different. In conclusion, normalized liver ADC can be useful in diagnosing liver fibrosis stage in patients with variable DWI acquisitions. Full article

18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (FDG-PET/CT) and contrast-enhanced computed tomography (CT) can be used for response evaluation in metastatic breast cancer (MBC). In this study, we aimed to review literature comparing the PET Response Criteria in Solid Tumors (PERCIST) with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with MBC. We made a systematic search in Embase, PubMed/Medline, and Cochrane Library using a modified PICO model. The population was MBC patients and the intervention was PERCIST or RECIST. Quality assessment was performed using the QUADAS-2 checklist. A total of 1975 articles were identified. After screening by title/abstract, 78 articles were selected for further analysis of which 2 duplicates and 33 abstracts/out of focus articles were excluded. The remaining 43 articles provided useful information, but only one met the inclusion and none of the exclusion criteria. This was a retrospective study of 65 patients with MBC showing one-year progression-free survival for responders versus non-responders to be 59% vs. 27% (p = 0.2) by RECIST compared to 64% vs. 0% (p = 0.0001) by PERCIST. This systematic literature review identified a lack of studies comparing the use of RECIST (with CE-CT) and PERCIST (with FDG-PET/CT) for response evaluation in metastatic breast cancer. The available sparse literature suggests that PERCIST might be more appropriate than RECIST for predicting prognosis in patients with MBC. Full article

The aim of the study was to analyze the thickness of individual retinal layers in patients with type 1 diabetes (T1D) in comparison to the control group and in relation to markers of diabetes metabolic control. The study group consisted of 111 patients with an average of 6-years of T1D duration. The control group included 36 gender- and age-matched individuals. In all patients optical coherence tomography (OCT) study was performed using HD-OCT Cirrus 5000 with evaluation of optic nerve head (ONH) parameters, thickness of retinal nerve fiber layer (RNFL) with its quadrants, macular full-thickness parameters, ganglion cells with inner plexus layer (GCIPL) and choroidal thickness (CT). Lower disc area value was observed in the study group as compared to controls (p = 0.0215). Negative correlations were found both between age at examination and rim area (R = −0.28, p = 0.0007) and between superior RNFL thickness and duration of diabetes (R = −0.20, p = 0.0336). Positive correlation between center thickness and SD for average glycemia (R = 0.30, p = 0.0071) was noted. Temporal CT correlated positively with age at examination (R = 0.21, p = 0.0127). The selected parameters the HD-OCT study may in the future serve as potential markers of preclinical phase of DR in patients with T1D. Full article

Leukemia is a fatal cancer and has two main types: Acute and chronic. Each type has two more subtypes: Lymphoid and myeloid. Hence, in total, there are four subtypes of leukemia. This study proposes a new approach for diagnosis of all subtypes of leukemia from microscopic blood cell images using convolutional neural networks (CNN), which requires a large training data set. Therefore, we also investigated the effects of data augmentation for an increasing number of training samples synthetically. We used two publicly available leukemia data sources: ALL-IDB and ASH Image Bank. Next, we applied seven different image transformation techniques as data augmentation. We designed a CNN architecture capable of recognizing all subtypes of leukemia. Besides, we also explored other well-known machine learning algorithms such as naive Bayes, support vector machine, k-nearest neighbor, and decision tree. To evaluate our approach, we set up a set of experiments and used 5-fold cross-validation. The results we obtained from experiments showed that our CNN model performance has 88.25% and 81.74% accuracy, in leukemia versus healthy and multi-class classification of all subtypes, respectively. Finally, we also showed that the CNN model has a better performance than other well-known machine learning algorithms. Full article

The need for diagnosing malignant melanoma in its earliest stages results in an increasing number of unnecessary excisions. Objective criteria beyond the visual inspection are needed to distinguish between benign and malignant melanocytic tumors in vivo. Fluorescence spectra collected during the prospective, multicenter observational study (“FLIMMA”) were retrospectively analyzed by the newly developed machine learning algorithm. The formalin-fixed paraffin-embedded (FFPE) tissue samples of 214 pigmented skin lesions (PSLs) from 144 patients were examined by two independent pathologists in addition to the first diagnosis from the FLIMMA study, resulting in three histopathological results per sample. The support vector machine classifier was trained on 17,918 fluorescence spectra from 49 lesions labeled as malignant (1) and benign (0) by three histopathologists. A scoring system that scales linearly with the number of the “malignant spectra” was designed to classify the lesion as malignant melanoma (score > 28) or non-melanoma (score ≤ 28). Finally, the scoring algorithm was validated on 165 lesions to ensure model prediction power and to estimate the diagnostic accuracy of dermatofluoroscopy in melanoma detection. The scoring algorithm revealed a sensitivity of 91.7% and a specificity of 83.0% in diagnosing malignant melanoma. Using additionally the image segmentation for normalization of lesions’ region of interest, a further improvement of sensitivity of 95.8% was achieved, with a corresponding specificity of 80.9%. Full article

We aimed to investigate whether preoperative MRI findings could predict the bladder neck location on postoperative cystography and recovery of urinary incontinence after robot-assisted laparoscopic radical prostatectomy (RALP). We retrospectively reviewed 270 consecutive patients who had complete preoperative data, including MRI, and underwent postoperative observation for more than three months. Preoperative MRI parameters consisted of the membranous urethral length (MUL) and pubic symphysis-prostate apex length (PAL) on sagittal images. The bladder neck location on a postoperative cystography was defined as the lowest extension of the tapering contrast medium in the bladder, and its relation to the pubic symphysis (above (higher group) and below (lower group) the middle of the pubic symphysis height) was evaluated. Those who required no pad or a safety pad were defined as being continent. PAL was significantly shorter in the higher group than that in the lower group (25.5 vs. 29.1 mm; p < 0.0001). The continent group at three months had a significantly longer MUL and shorter PAL than those in the incontinent group (8.1 vs. 6.7 mm; p < 0.05, and 26.0 vs. 28.1 mm; p < 0.05, respectively). Preoperative MRI parameters could predict the bladder neck location on postoperative cystograms and the recovery of urinary incontinence after RALP. Full article

Biological effects of low-dose ionizing radiation (IR) have been unclear until now. Saliva, because of the ease of collection, could be valuable in studying low-dose IR effects by means of surface-enhanced Raman spectroscopy (SERS). The objective of our study was to compare the salivary SER spectra recorded before and after low-dose IR exposure in the case of pediatric patients (PP). Unstimulated saliva was collected from ten PP before and after irradiation with a cone beam computed tomography (CBCT) machine used for diagnostic purposes. The SERS measurements have been recorded on dried saliva samples using a solid nanosilver plasmonic substrate synthesized using an original method developed in our laboratory. The experimental results showed that salivary SER spectra are dominated by three vibrational bands (441,735 and 2107 cm⁻¹) that can be assigned to bending and stretching vibrations of salivary thiocyanate (SCN-). After exposure, an immediate increase of vibrational bands assigned to SCN- has been recorded in the case of all samples, probably as a result of IR interaction with oral cavity. This finding suggests that SCN- could be used as a valuable biomarker for the detection and identification of low-dose radiation effects. Full article

Portable and wearable medical instruments are poised to play an increasingly important role in health monitoring. Mobile spirometers are available commercially, and are used to monitor patients with advanced lung disease. However, these commercial monitors have a fixed product architecture determined by the manufacturer, and researchers cannot easily experiment with new configurations or add additional novel sensors over time. Spirometry combined with exhaled breath metabolite monitoring has the potential to transform healthcare and improve clinical management strategies. This research provides an updated design and benchmark testing for a flexible, portable, open access architecture to measure lung function, using common Arduino/Android microcontroller technologies. To demonstrate the feasibility and the proof-of-concept of this easily-adaptable platform technology, we had 43 subjects (healthy, and those with lung diseases) perform three spirometry maneuvers using our reconfigurable device and an office-based commercial spirometer. We found that our system compared favorably with the traditional spirometer, with high accuracy and agreement for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), and gas measurements were feasible. This provides an adaptable/reconfigurable open access “personalized medicine” platform for researchers and patients, and new chemical sensors and other modular instrumentation can extend the flexibility of the device in the future. Full article

Research in computer-aided diagnosis (CAD) and the application of artificial intelligence (AI) in the endoscopic evaluation of the gastrointestinal tract is novel. Since colonoscopy and detection of polyps can decrease the risk of colon cancer, it is recommended by multiple national and international societies. However, the procedure of colonoscopy is performed by humans where there are significant interoperator and interpatient variations, and hence, the risk of missing detection of adenomatous polyps. Early studies involving CAD and AI for the detection and differentiation of polyps show great promise. In this appraisal, we review existing scientific aspects of AI in CAD of colon polyps and discuss the pitfalls and future directions for advancing the science. This review addresses the technical intricacies in a manner that physicians can comprehend to promote a better understanding of this novel application. Full article

Using next-generation sequencing to decipher the molecular mechanisms underlying aberrant rheumatoid arthritis synovial fibroblasts (RASF) activation, we performed transcriptome-wide RNA-seq and small RNA-seq on synovial fibroblasts from rheumatoid arthritis (RA) subject and normal donor. Differential expression of mRNA and miRNA was integrated with interaction analysis, functional annotation, regulatory network mapping and experimentally verified miRNA–target interaction data, further validated with microarray expression profiles. In this study, 3049 upregulated mRNA and 3552 downregulated mRNA, together with 50 upregulated miRNA and 35 downregulated miRNA in RASF were identified. Interaction analysis highlighted contribution of miRNA to altered transcriptome. Functional annotation revealed metabolic deregulation and oncogenic signatures of RASF. Regulatory network mapping identified downregulated FOXO1 as master transcription factor resulting in altered transcriptome of RASF. Differential expression in three miRNA and corresponding targets (hsa-miR-31-5p:WASF3, hsa-miR-132-3p:RB1, hsa-miR-29c-3p:COL1A1) were also validated. The interactions of these three miRNA–target genes were experimentally validated with past literature. Our transcriptomic and miRNA interactomic investigation identified gene signatures associated with RASF and revealed the involvement of transcription factors and miRNA in an altered transcriptome. These findings help facilitate our understanding of RA with the hope of serving as a springboard for further discoveries relating to the disease. Full article

Less time-consuming, easy-to-apply and more reliable cognitive screening tests are essential for use in primary care. The aim of this study was to investigate the diagnostic value of the Turkish version of the Rapid Cognitive Screen (RCS-T) and Triple Test individually and the combination of RCS-T with each sign and Triple Test to screen elderly patients for cognitive impairment (CI). A total of 357 outpatients aged 60 or older, who underwent comprehensive geriatric assessment, were included in the study. Presence or absence of attended alone sign (AAS), head-turning sign, and applause sign was investigated. The mean age of the patients was 74.29 ± 7.46. Of those, 61 patients (28 men, 33 women) had Alzheimer’s disease (AD), 59 patients had mild cognitive impairment (MCI) (29 men, 30 women), and 237 (80 men, 157 women) were cognitively robust. The sensitivity of the combination of RCS-T and negative for AAS for CI, AD and MCI is 0.79, 0.86 and 0.61, respectively; the specificity was 0.92, 0.93 and 0.92, respectively; and the positive and negative predictive values revealed good diagnostic accuracy. The combination of RCS-T and negative for AAS is a simple, effective and rapid way to identify possible CI in older adults. Full article

purpose: Liquid biopsy is becoming increasingly important as a guide for selecting new drugs and determining their efficacy. In urological cancer, serum markers for renal cell and urothelial cancers has made the development of liquid biopsy for these cancers strongly desirable. Liquid biopsy is less invasive than conventional tissue biopsy is, enabling frequent biopsies and, therefore, is considered effective for monitoring the treatment course. Circulating tumor cells (CTCs) are a representative liquid biopsy specimen. In the present study, we focused on developing our novel technology for capturing renal cell cancer (RCC)-CTCs using an anti-G250 antibody combined with new devices. Basic experiments of our technology showed that it was possible to detect RCC-CTC with a fairly high accuracy of about 95%. Also, RCC-CTC was identified in the peripheral blood of actual RCC patients. Additionally, during the treatment course of the RCC patient, change in the number of RCC-CTC was confirmed in one case. We believe that the technology we developed will be useful for determining the treatment efficacy and drug selection for the treatment of renal cell cancer (RCC). In order to solve issues such as thresholds setting of this technology, large-scale clinical trials are expected. Full article

Full completion of cognitive screening tests can be problematic in the context of a stroke. Our aim was to examine the completion of various brief cognitive screens and explore reasons for untestability. Data were collected from consecutive stroke admissions (May 2016–August 2018). The cognitive assessment was attempted during the first week of admission. Patients were classified as partially untestable (≥1 test item was incomplete) and fully untestable (where assessment was not attempted, and/or no questions answered). We assessed univariate and multivariate associations of test completion with: age (years), sex, stroke severity (National Institutes of Health Stroke Scale (NIHSS)), stroke classification, pre-morbid disability (modified Rankin Scale (mRS)), previous stroke and previous dementia diagnosis. Of 703 patients admitted (mean age: 69.4), 119 (17%) were classified as fully untestable and 58 (8%) were partially untestable. The 4A-test had 100% completion and the clock-draw task had the lowest completion (533/703, 76%). Independent associations with fully untestable status had a higher NIHSS score (odds ratio (OR): 1.18, 95% CI: 1.11–1.26), higher pre-morbid mRS (OR: 1.28, 95% CI: 1.02–1.60) and pre-stroke dementia (OR: 3.35, 95% CI: 1.53–7.32). Overall, a quarter of patients were classified as untestable on the cognitive assessment, with test incompletion related to stroke and non-stroke factors. Clinicians and researchers would benefit from guidance on how to make the best use of incomplete test data. Full article

Our laboratory performs procalcitonin (PCT) assays on a Brahms KRYPTOR analyzer with the Brahms PCT sensitive Kryptor kit. In this study, we wanted to compare the assays obtained in this way with the ones performed on the LIAISON^® XL. From January to May 2017, 171 samples were analyzed, of which 65 from female patients (age: 22–98 years) and 106 from male patients (age: 16–97 years). The PCT determination was performed using the LIAISON^® XL and KRYPTOR analyzers, by chemiluminescence (Chemiluminescence immunoassay—CLIA) (LIAISON^® BRAHMS PCT^® II GEN) and immunofluorescence (Brahms PCT sensitive Kryptor) assay, respectively. For the LIAISON^® BRAHMS PCT^® II GEN, 52% of the results were placed between 0.0 and 0.5 ng/mL, 18% between 0.5 and 2.0 ng/mL, and 30% between 2.0 and 100 ng/mL; the mean was 4.09 ng/mL, the median 0.456 ng/mL, the maximum value 97.2 ng/mL, and the minimum value 0.02 ng/mL. For the Brahms PCT sensitive Kryptor, 55% of the results were positioned between 0.0 and 0.5 ng/mL, 21% between 0.5 and 2.0 ng/mL, and 24% between 2.0 and 100 ng/mL; the mean was 3.72 ng/mL, the median 0.39 ng/mL, the maximum value 103 ng/mL, and the minimum value 0.01 ng/mL. The mean of the results obtained with the two methods showed no significant differences (3.717 for Kryptor and 4.094 for LIAISON^®). PCT assay with Brahms reagents, both on the Kryptor and LIAISON^®XL platforms, offers excellent performance in terms of sensitivity and specificity. Full article