Background:Metabolomics has shown promise in gastric cancer (GC) detection. This research sought to identify whether GC has a unique urinary metabolomic profile compared with benign gastric disease ...(BN) and healthy (HE) patients.Methods:Urine from 43 GC, 40 BN, and 40 matched HE patients was analysed using 1 H nuclear magnetic resonance (1 H-NMR) spectroscopy, generating 77 reproducible metabolites (QC-RSD <25%). Univariate and multivariate (MVA) statistics were employed. A parsimonious biomarker profile of GC vs HE was investigated using LASSO regularised logistic regression (LASSO-LR). Model performance was assessed using Receiver Operating Characteristic (ROC) curves.Results:GC displayed a clear discriminatory biomarker profile; the BN profile overlapped with GC and HE. LASSO-LR identified three discriminatory metabolites: 2-hydroxyisobutyrate, 3-indoxylsulfate, and alanine, which produced a discriminatory model with an area under the ROC of 0.95.Conclusions:GC patients have a distinct urinary metabolite profile. This study shows clinical potential for metabolic profiling for early GC diagnosis.
Low grade gliomas are the most frequent brain tumors in children and encompass a spectrum of histologic entities which are currently assigned World Health Organisation grades I and II. They differ ...substantially from their adult counterparts in both their underlying genetic alterations and in the infrequency with which they transform to higher grade tumors. Nonetheless, children with low grade glioma are a therapeutic challenge due to the heterogeneity in their clinical behavior - in particular, those with incomplete surgical resection often suffer repeat progressions with resultant morbidity and, in some cases, mortality. The identification of up-regulation of the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway as a near universal feature of these tumors has led to the development of targeted therapeutics aimed at improving responses while mitigating patient morbidity. Here, we review how molecular information can help to further define the entities which fall under the umbrella of pediatric-type low-grade glioma. In doing so we discuss the specific molecular drivers of pediatric low grade glioma and how to effectively test for them, review the newest therapeutic agents and their utility in treating this disease, and propose a risk-based stratification system that considers both clinical and molecular parameters to aid clinicians in making treatment decisions.
As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination. To interrupt transmission, changes in control strategies are likely to ...require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings. Currently available immunochromatographic lateral flow rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/µL making them insufficiently sensitive for detecting all carriers. Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time. This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination.
Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely ...available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints.
Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry.
Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene.
The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions.
Eosinophilic esophagitis (EoE) is a histologically “patchy” disease with uneven eosinophil distribution along the esophagus, posing a dilemma for histologically analyzing endoscopic biopsy samples, ...especially when biopsy samples are limited to only the distal esophagus.
We investigated whether molecular mRNA profiling of a distal esophageal biopsy sample predicts eosinophilia in the proximal esophagus.
Esophageal biopsy samples (n = 507) from subjects with EoE were collected from multiple institutions, spanning adults and pediatric patients. Subjects were grouped on the basis of distinct distal (D) and proximal (P) eosinophil counts (D+P+, D+P–, D-P+, and D–P–, with + and – defined as ≥15 or <15 eosinophils/hpf, respectively). Molecular profiles were assessed by using the EoE Diagnostic Panel (EDP), a set of 96 esophageal transcripts used to derive the EDP score.
The distal EDP score was correlated with proximal eosinophil levels (r = –0.73; P < .0001). EDP analysis of a histologically negative distal biopsy sample predicted the presence of proximal esophagitis with high sensitivity (85%). In a 2-year follow-up focusing on the cases with discordant histologic and EDP results, histologically negative patients (D–P–) had higher rates of EoE relapse when the EDP was positive than when the EDP was negative (odds ratio = 11; P = .003), indicating predictive medicine capacity.
EDP analysis of a single distal esophageal biopsy sample predicts remote inflammation in patients with spatially heterogeneous eosinophilia and disease relapse in patients with histologic remission, providing diagnostic merit and predictive medicine capacity for molecular diagnosis of EoE.
Acute gastroenteritis (AGE) is caused by a wide range of pathogens. Culture methods for the detection of bacterial pathogens is time consuming and labour intensive. This study compared a ...same-day-to-result commercial molecular method using BD Max™ Enteric Bacterial Panel against conventional culture and laboratory-developed PCR assays (LDTs), and characterised the epidemiology of bacterial AGE in Singapore.
PCRs for Campylobacter spp., Salmonella spp., Shigella spp./Enteroinvasive Escherichia coli (EIEC) and Shiga toxin-producing E. coli (STEC)/Shigella dysenteriae were performed on the BD Max™ platform. Concurrent routine bacterial culture (“reference standard”) was performed for Campylobacter, Salmonella, Shigella, Vibrio and Aeromonas spp. In the event of a discrepancy, an “expanded reference standard” (bacterial culture with LDT) was used.
There were 299 stool specimens in the study, with no bacterial pathogens detected in 190 samples (63.5%). The positive samples (n = 109,36.5%) were detected with Salmonella (n = 57,19.1%), Campylobacter (n = 28,9.4%), Vibrio parahaemolyticus (n = 6,2.0%), Shigella/EIEC (n = 6,2.0%), ETEC (n = 4,1.3%), STEC (n = 2,0.7%), Aeromonas (n = 2,0.7%), Plesiomonas shigelloides (n = 1,0.3%) and 3(1.0%) co-infections. Compared to the “expanded reference standard”, conventional culture missed 38/112 (33.9%) pathogens. Conversely, testing by BD Max™ alone failed to detect 17 pathogens. BD Max™ reported seven (2.3%) false-positive results.
BD Max™ increased the detection rate of bacterial AGE pathogens in the panel, but was limited by the absence of detection capability for Vibrio and Aeromonas spp.
•Acute gastroenteritis (AGE) is caused by a wide range of pathogens.•Culture methods for bacterial detection are time-consuming and labour intensive.•BD Max™ Enteric Bacterial Panel increases detection yield with shorter turnaround.•Combination of culture for Vibrio and Aeromonas with BD Max™ usage is recommended.
The clinical and economical burdens of invasive fungal diseases (IFDs) remain substantial despite advances in diagnostics and therapeutics. Major challenges in diagnosis of IFDs are difficulty in ...obtaining appropriate specimens for histopathology examination and prolonged turnaround time for fungal cultures. Molecular assays for direct detection of fungal DNA from sterile sites such as blood can provide definitive diagnosis of IFDs in a reduced turnaround time. The ePlex BCID-FP Panel from GenMark Diagnostics, a member of the Roche corporation, is currently the largest commercial multiplex fungal pathogen identification panel for blood cultures and has potential for early optimization of treatment and improvement of patient outcomes.
This article provides a comprehensive review of the ePlex BCID-FP Panel including its market profile, assay performance characteristics, clinical profile, and cost-effectiveness. Other currently available diagnostic assays for IFDs are also discussed.
Although molecula- based assays for detection of fungal pathogens such as the ePlex BCID-FP Panel have increased diagnostic capacity for IFDs and provide timelier results compared to the conventional methods, there are still unmet clinical needs in the diagnosis of IFDs. Further development of novel assays is needed to fulfill the diagnostic gaps.
Precision cancer medicine (PCM) holds great promises to offer more effective therapies to patients based on molecular profiling of their individual tumours. Although the PCM approach seems intuitive, ...multiple conceptional and structural challenges interfere with the broad implementation of PCM into clinical practice. Accordingly, concerted national and international efforts are needed to guide the further development and broad adoption of PCM in Germany. With support of the ‘German Cancer Aid’ (Deutsche Krebshilfe DKH) a task force ‘Molecular Diagnostics and Therapy’ was implemented. In two workshops supported by the DKH, delegates from the fourteen comprehensive cancer centresidentified key topics essential to implement quality-guided, harmonized and adaptable PCM. Based on an online questionnaire and using a modified Delphi approach, nine statements were drafted and evaluated within the group. These statements could serve as a basis to define a collaborative strategy for PCM in the future with the aim to sustain and further improve its quality.
•This consenus statement originated from collaborative efforts of all fourteen Comprehensive Cancer Centres in the German Cancer Aid network.•The consensus statement is based on all centres' consent due to implementation of a modified Delphi process.•This consensus statement will serve as a framework to establish sustainable structures for precision cancer medicine in Germany.
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