Diagnostics — Open Access Journal

Sepsis, a dysregulated host response to infection, is a major health burden in terms of both mortality and cost. The difficulties clinicians face in diagnosing sepsis, alongside the insufficiencies of diagnostic biomarkers, motivate the present study. This work develops a machine-learning-based sepsis diagnostic for a high-risk patient group, using a geographically and institutionally diverse collection of nearly 500,000 patient health records. Using only a minimal set of clinical variables, our diagnostics outperform common severity scoring systems and sepsis biomarkers and benefit from being available immediately upon ordering. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. PDAC is the fourth leading cause of death in the United States and Japan based on epidemiological data. Early detection of PDAC is very important to improve the prognosis of PDAC.Early detection of pancreatic ductal adenocarcinoma (PDAC) requires further examination after selecting cases with risk factors for the condition, such as family history, hereditary pancreatic carcinoma syndrome, intraductal papillary mucinous neoplasms, or chronic pancreatitis. The Japan Study Group on the Early Detection of Pancreatic Cancer has investigated and clarified the clinicopathological features for the early diagnosis of PDAC. In Japan, an algorithm for the early diagnosis of PDAC, which utilized the cooperation of local clinics and regional general hospitals, has been a breakthrough in the detection of early-stage PDAC. Further approaches for the early diagnosis of PDAC are warranted. Full article

18F-fluorothymidine (18F-FLT) is a radiolabeled thymidine analog that has been reported to help monitor tumor proliferation and has been studied in primary brain tumors; however, knowledge about 18F-FLT positron emission tomography/computed tomography (PET/CT) in metastatic brain lesions is limited. The purpose of this study is to evaluate the performance of 18F-FLT-PET/CT in metastatic brain lesions. A total of 20 PET/CT examinations (33 lesions) were included in the study. Semiquantitative analysis was performed: standard uptake value (SUV) with the utilization of SUVmax, tumor-to-background ratio (T/B), SUVpeak, SUV1cm³, SUV0.5cm³, SUV50%, SUV75%, PV50% (volume × SUV50%), and PV75% (volume × SUV75%) were calculated. Sensitivity, specificity, and accuracy for each parameter were calculated. Optimal cutoff values for each parameter were obtained. Using a receiver operating characteristic (ROC) curve analysis, the optimal cutoff values of SUVmax, T/B, and SUVpeak for discriminating active from non-active lesions were found to be 0.615, 4.21, and 0.425, respectively. In an ROC curve analysis, the area under the curve (AUC) is higher for SUVmax (p-value 0.017) compared to the rest of the parameters, while using optimal cutoff T/B shows the highest sensitivity and accuracy. PVs (proliferation × volumes) did not show any significance in discriminating positive from negative lesions. 18F-FLT-PET/CT can detect active metastatic brain lesions and may be used as a complementary tool. Further investigation should be performed. Full article

Background:While left ventricular ejection fraction (LVEF) has been shown to have prognostic value in ischemic cardiomyopathy (ICMX) patients, right ventricular ejection fraction (RVEF) has not been systematically evaluated in either ICMX or non-ischemic cardiomyopathy (NICMX) patients. Moreover, an accurate estimation of RVEF is problematic due to the geometry of the right ventricle (RV). Over the years, there have been improvements in the resolution, image acquisition and post-processing software for cardiac magnetic resonance imaging (CMR), such that CMR has become the “gold standard” for measuring RV volumetrics and RVEF. We hypothesize that CMR defines RVEF more so than LVEF and might have prognostic capabilities in ischemic and non-ischemic cardiomyopathy patients (ICMX and NICMX). Methods: Patients that underwent CMR at our institution between January 2005 and October 2012 were retrospectively selected if three-dimensional (3D) LVEF < 35%. Patients were further divided into ICMX and NICMX groups. The electronic medical record (EMR) database inquiry determined all-cause mortality and major adverse cardiovascular events (MACE). Additionally, a Social Security Death Index (SSI) database inquiry was performed to determine all-cause mortality in patients who were lost to follow-up. Patients were further sub-grouped on the basis of 3D RVEF ≥ 20%. Separately, patients were sub-grouped by LVEF ≥ 20% in both ICMX and NICMX cases. A cut-off of ≥20% was chosen for the RVEF based on the results of prior studies showing significance based on Kaplan–Meier (KM) survival curves. Cumulative event rates were estimated for each subgroup using the KM analysis and were compared using the log-rank test. The 3D RV/LVEFs were compared to all-cause mortality and MACE. ICMX patients were defined using the World Health Organization (WHO) criteria. Results: From a 7000-patient CMR database, 753 heart failure patients were selected. Eighty-seven patients met WHO definition of ICMX and NICMX (43 ICMX and 44 NICMX). The study patients were followed for a median of 3 years (Interquartile range or IQR 1.5–6.5 years). The mean age of patients was 58 ± 13 years; 79% were male. In ICMX, mean 3D LVEF was 21% ± 6% and mean 3D RVEF was 38% ± 14%, while for NICMX, mean 3D LVEF was 16% ± 6% and mean 3D RVEF was 30% ± 14% (p < 0.005 for intra- and inter-group comparison). It should be noted that LVEF < RVEF in both groups and the ejection fraction (EF) in NICMX was less than the corresponding EF in ICMX. Overall mortality was higher in ICMX than NICMX (12/40, 30% vs. 7/43, 16%; p < 0.05). Patients were stratified based on both RVEF and LVEF with a threshold of EF ≥ 20% separately. RVEF but not LVEF was a significant predictor of death for NICMX (χ² = 8; p < 0.005), while LVEF did not predict death in ICMX (χ² = 2, p = not significant). Similarly, time to MACE was predicted by RVEF for NICMX (χ² = 9; p < 0.005) but not by LVEF in ICMX (χ² = 1; p = NS). Importantly, RVEF, while predictive of NICMX MACE, did not emerge as a predictor of survival or MACE in ICMX. Conclusions: Via 3D CMR in non-ischemic CMX patients, RVEF has important value in predicting death and time to first MACE while 3D LVEF is far less predictive. Full article

Backgrounds: Endoscopic ultrasonography (EUS) is used to observe the stricture of the main pancreatic duct (MPD) and in diagnosing pancreatic cancer (PC). We investigate the findings on EUS by referring to the histopathological findings of resected specimens. Materials and Methods: Six patients with carcinoma in situ (CIS) and 30 patients with invasive carcinoma of 20 mm or less were included. The preoperative EUS findings were classified as follows. A1: Simple stricture type—no findings around the stricture; A2: Hypoecho stricture type—localized hypoechoic area without demarcation around the stricture; A3: Tumor stricture type—tumor on the stricture; B: Dilation type—the dilation of the pancreatic duct without a downstream stricture; C: Parenchymal tumor type—tumor located apart from the MPD. Results: Classes A1 and A2 consisted of 2 CISs, and 4 invasive carcinomas included two cases smaller than 5 mm in diameter. Most of the cancers classified as A3 or C were of invasive carcinoma larger than 5 mm in diameter. All cancers classified as B involved CIS. Serial pancreatic-juice aspiration cytologic examination (SPACE) was selected for all types of cases, with a sensitivity of 92.0%, while EUS-guided fine needle aspiration cytology (EUS-FNA) was only useful for invasive carcinoma, and its sensitivity was 66.7%. Conclusions: Stricture without a tumor could be a finding for invasive PC and pancreatic duct dilation without a downstream stricture could be a finding indicative of CIS. Carcinoma smaller than 5 mm in diameter could not be recognized by EUS. SPACE had a high sensitivity for diagnosing small PC. Full article

Myofascial temporomandibular disorders (TMD) are the most common cause of chronic pain in the orofacial region. Microdialysis has been used to study metabolic changes in the human masseter muscle. The insertion of the microdialysis probe causes acute tissue trauma that could affect the metabolic milieu and thereby influence the results when comparing healthy subjects to those with TMD. This study aimed to investigate the levels of serotonin and glutamate during the acute tissue trauma period in healthy subjects and in patients with TMD. Microdialysis was carried out in 15 patients with TMD and 15 controls, and samples were collected every 20 min during a period of 140 min. No significant alterations of serotonin or glutamate were observed over the 2 h period for the healthy subjects. For the TMD group, a significant decrease in serotonin was observed over time (p < 0.001), followed by a significant increase between 120 and 140 min (p < 0.001). For glutamate, a significant reduction was observed at 40 min compared to baseline. The results showed that there was a spontaneous increase of serotonin 2 h after the insertion of the catheter in patients with TMD. In conclusion, the results showed that there are differences in the masseter muscle levels of serotonin and glutamate during acute nociception in patients with myofascial TMD compared to healthy subjects. Full article

MET is a receptor tyrosine kinase (RTK) that plays important roles in carcinogenesis. Despite being frequently overexpressed in cancer, clinical responses to targeting this receptor have been limited. Recently novel splicing mutations involving the loss of exon 14 (called METex14 skipping) have emerged as potential biomarkers to predict for responsiveness to targeted therapies with Met inhibitors in non-small cell lung cancer (NSCLC). Currently, the diverse genomic alterations responsible for METex14 skipping pose a challenge for routine clinical diagnostic testing. In this report, we examine three different methodologies to detect METex14 and assess their potential utility for use as a diagnostic assay for both the identification of METex14 and intra-tumoural distribution in NSCLC. Full article

Axillary lymph node status is the single most important prognostic indicator in patients with breast cancer. Axillary lymph node dissection, the traditional method of staging breast cancer, is associated with significant morbidity. Sentinel lymph node biopsy has become standard in patients being treated for breast cancer with clinically negative lymph nodes. There is considerable variation in the medical literature regarding technical approaches to sentinel lymph node biopsy in patients with breast cancer. The purpose of this article is to describe our preferred approaches to sentinel lymph node biopsy with a review of the literature. Full article

Tonsillectomy is a commonly performed surgery in the daily practice of an otorhinolaryngologist. For patients as well as health professionals, the best known complication is post-operative bleeding. Among the less noted, but potentially life-threatening, complications are the development of subcutaneous emphysema and the presence of bacteremia due to group A hemolytic streptococci. In this report, we describe a severely complicated clinical course after an uncomplicated adenotonsillectomy in a young boy. Increased awareness of relatively unknown complications after adenotonsillectomy amongst surgeons, pediatricians and anesthesiologists is desirable to facilitate rapid diagnosis and adequate treatment in order to prevent life-threatening situations. Full article

Bacterial blood stream infections (BSI) are a common cause of mortality and morbidity globally. As the causative agents and the resulting treatment decisions vary, near-patient testing and surveillance tools are necessary to monitor bacterial causes and resistance to antimicrobial agents. The gold standard to identify BSIs is blood culture (BC), a methodology not widely available in resource-limited settings. The aim of the study was to map out a target product profile of a simplified BC system (SBCS) to inform product development efforts. To identify the desired characteristics of a SBCS, we enlisted a small group of specialists working in Africa and Asia. Questions were used to understand challenges and how these constraints inform system requirements. The specialists were infectious disease physicians, public health/clinical microbiologists, clinical researchers, and technology experts with different geographical backgrounds. All suggested that BC should ideally be available at the district hospital level. Many of the same operational challenges, such as limited availability of culture bottles, electricity and internet connectivity, profuse dust, the lack of ambient temperature control, and human capacity constraints were identified across the different regions. BCs, although the accepted gold standard for diagnosis of BSIs, are not widely available outside of reference/research centers in Africa and Asia. To extend the reach of this important tool, it is crucial to engage product developers and academic research partners to develop accessible alternatives. Full article

The cell-free genomic DNA (gDNA) concentration in serum ranges from 1500 to 7500 copies/mL within 2 h after phlebotomy (6–24 times the concentration observed in plasma). Here, we aimed to evaluate the gDNA size distribution in serum with time after coagulation and to test if crude serum can be directly used as a source of gDNA for qPCR. Next, we investigated if single nucleotide polymorphisms (SNPs) could be genotyped directly from the crude serum isolated from capillary blood using a hand-powered paper centrifuge. All tested PCR targets (65, 100, 202 and 688 base pairs) could be successfully amplified from DNA extracted from serum, irrespective of their amplicon size. The observed qPCR quantitation cycles suggested that the genomic DNA yield increased in serum with incubation at room temperature. Additionally, only 65 and 101 base pair qPCR targets could be amplified from crude serum soon after the coagulation. Incubation for 4 days at room temperature was necessary for the amplification of PCR targets of 202 base pairs. The 688 base pair qPCR target could not be amplified from serum directly. Lastly, serum was successfully separated from capillary blood using the proposed paper centrifuge and the genotypes were assigned by testing the crude serum using allele-specific qPCR, producing small amplicon sizes in complete agreement with the genotypes assigned by testing the DNA extracted from whole blood. The serum can be used directly as the template in qPCR for SNP genotyping, especially if small amplicon sizes are applied. This shortcut in the SNP genotyping process could further molecular point-of-care diagnostics due to elimination of the DNA extraction step. Full article

Depression is a mental disorder characterized by recurrent sadness and loss of interest in the enjoyment of the positive aspects of life, in addition to fatigue, causing inability to perform daily activities, which leads to a loss of quality of life. To monitor depression (unipolar and bipolar patients), traditional methods rely on reports from patients; nevertheless, bias is commonly present in them. To overcome this problem, Ecological Momentary Assessment (EMA) reports have been widely used, which include data of the behavior, feelings and other types of activities recorded almost in real time through the use of portable devices and smartphones containing motion sensors. In this work a methodology was proposed to detect depressive subjects from control subjects based in the data of their motor activity, recorded by a wearable device, obtained from the “Depresjon” database. From the motor activity signals, the extraction of statistical features was carried out to subsequently feed a random forest classifier. Results show a sensitivity value of 0.867, referring that those subjects with presence of depression have a degree of 86.7% of being correctly classified, while the specificity shows a value of 0.919, referring that those subjects with absence of depression have a degree of 91.9% of being classified with a correct response, using the motor activity signal provided from the wearable device. Based on these results, it is concluded that the motor activity allows distinguishing between the two classes, providing a preliminary and automated tool to specialists for the diagnosis of depression. Full article

This paper reviews non-invasive blood glucose measurements via dielectric spectroscopy at microwave frequencies presented in the literature. The intent is to clarify the key challenges that must be overcome if this approach is to work, to suggest some possible ways towards addressing these challenges and to contribute towards prevention of unnecessary ‘reinvention of the wheel’. Full article

Invasive catheterization is associated with a low risk of serious complications. However, although it is the gold standard for measuring pressure gradients, it induces changes to blood flow and requires significant resources. Therefore, non-invasive alternatives are urgently needed. Pressure gradients are routinely estimated non-invasively in clinical settings using ultrasound and calculated with the simplified Bernoulli equation, a method with several limitations. A PubMed literature search on validation of non-invasive techniques was conducted, and studies were included if non-invasively estimated pressure gradients were compared with invasively measured pressure gradients in vivo. Pressure gradients were mainly estimated from velocities obtained with Doppler ultrasound or magnetic resonance imaging. Most studies used the simplified Bernoulli equation, but more recent studies have employed the expanded Bernoulli and Navier–Stokes equations. Overall, the studies reported good correlation between non-invasive estimation of pressure gradients and catheterization. Despite having strong correlations, several studies reported the non-invasive techniques to either overestimate or underestimate the invasive measurements, thus questioning the accuracy of the non-invasive methods. In conclusion, more advanced imaging techniques may be needed to overcome the shortcomings of current methods. Full article

Radiogenomics is a computational discipline that identifies correlations between cross-sectional imaging features and tissue-based molecular data. These imaging phenotypic correlations can then potentially be used to longitudinally and non-invasively predict a tumor’s molecular profile. A different, but related field termed radiomics examines the extraction of quantitative data from imaging data and the subsequent combination of these data with clinical information in an attempt to provide prognostic information and guide clinical decision making. Together, these fields represent the evolution of biomedical imaging from a descriptive, qualitative specialty to a predictive, quantitative discipline. It is anticipated that radiomics and radiogenomics will not only identify pathologic processes, but also unveil their underlying pathophysiological mechanisms through clinical imaging alone. Here, we review recent studies on radiogenomics and radiomics in liver cancers, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastases to the liver. Full article

We present a case demonstrating the diagnostic work-up of a patient undergoing azathioprine treatment for inflammatory bowel disease (IBD), diagnosed with an acute cytomegalovirus (CMV) infection and CMV colitis. An ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) performed 2 weeks after debut of symptoms revealed pathological ¹⁸F-FDG uptake in the left side of the colon mucosa, mimicked activity of IBD. However, a diagnosis of CMV colitis was based on the presence of CMV IgM antibodies, a seroconversion of CMV IgG antibodies, presence of CMV DNA in plasma and the finding af CMV DNA in biopsies from the intestinal mucosa. The patient responded to treatment with ganciclovir. This case highlights that a positive ¹⁸F-FDG PET/CT scan of the colon can be due to CMV colitis. Full article

Pancreatic cancer (PC) is the fourth leading cause of cancer-related death with a 5-year survival rate less than 10%. In the absence of effective screening methods, such as blood markers, most clinical diagnoses of PC are made at an advanced stage. However, early stage PC is associated with a more favorable five-year survival rate of 85.8% for stage 0, and 68.7% for stage IA. Transabdominal ultrasound (US) is frequently used as a first-line diagnostic tool in the clinical setting and a preferred modality for routine medical evaluations for asymptomatic individuals. Recently published Japanese data show that most PCs diagnosed in early stage had US findings, such as dilated main pancreatic ducts or pancreas cysts. For surveillance of high-risk individuals, such as those with an intraductal papillary mucinous neoplasm (IPMN), US is an ideal modality in terms of its non-invasive and cost-effective nature. However, the diagnostic performance of ultrasound varies greatly by the operator’s experience and the patient’s condition. This article reviews the present situation of early diagnosis of pancreatic cancer by US, along with tips for improving visualization of the pancreas. Full article