Noninvasive Diagnostic Tests Research Articles

Detection of microRNA in urine to identify patients with endometrial cancer: a feasibility study

ObjectiveTo find dysregulated urinary microRNAs associated with endometrial cancer as a first step in finding a non-invasive new diagnostic biomarker. The second objective is to determine the correlation of urinary...

Overview of miRNAs for the non-invasive diagnosis of endometriosis: evidence, challenges and strategies. A systematic review.

ABSTRACTObjective The aim of the study was to assess the evidence on miRNAs as biomarkers for the diagnosis of endometriosis, as well as to provide insights into the challenges and strategies associated with the use of these molecules as accessible tools in clinical practice.Methods Systematic review conducted on PubMed®, Latin American and Caribbean Health Sciences Literature (LILACS), MEDLINE® and Web of Science databases using the search terms endometriosis (all fields) AND miRNA (all fields), evaluating all publication up to May 2019.Results Most miRNAs found to be dysregulated in this study were harvested from tissue samples, which precludes their use as a non-invasive diagnostic test. However, differential expression of 62 miRNAs was reported in samples that may be used for non-invasive diagnosis of endometriosis, such as blood, serum and plasma.Conclusion Despite the identification of several candidates, studies are investigatory in nature and have been conducted with small number of samples. Also, no particular miRNA has been validated for diagnostic purposes so far. Studies based primarily on biological samples and applicable to translational research are warranted. Large databases comprising information on sample type and the use of saliva and vaginal fluid for miRNAs identification may prove essential to overcome current barriers to diagnosis of endometriosis.

Assessing the Severity of Aortic Regurgitation Using 3-D Color Doppler Echocardiography

Transthoracic echocardiography (TTE) is the most common non-invasive diagnostic test that is being used all around the world to assess the heart. With the development of three-dimensional echocardiography over the last decade, accurate, and detailed imaging has allowed for significant improvements in the capability of assessing and understanding cardiac pathology.

Colonic Health in Hospitalized Horses Treated with Non-Steroidal Anti-Inflammatory Drugs – A Preliminary Study

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause right dorsal colitis, but longitudinal clinical studies are lacking. This study investigates whether NSAID treated horses develop right dorsal colonic pathology in a clinical setting. Non-gastrointestinal hospitalized horses treated with NSAIDs >4 days, and untreated hospital-owned teaching horses and non-gastrointestinal client-owned hospitalized horses were included. All horses were monitored over time with clinical examinations (focusing on presence of colic, depression, reduced appetite, unstructured feces), ultrasonographic intestinal wall measurements, fecal occult blood tests (semi-quantitative results), and blood analysis (total protein and albumin concentrations, white blood cell and neutrophil counts). Outcomes were recorded as “ultrasonographically thickened right dorsal colon (RDC) walls”, “colitis” and “right dorsal colitis”. Findings over time were compared to baseline values and to control horses. Seventeen NSAID treated horses and 5 controls were included. NSAID treated horses developed thickened RDC walls (4/9), and subclinical and mild colitis (9/11) and right dorsal colitis (4/10), whereas all control horses remained healthy. The first changes were identified on treatment day 2. RDC walls of treated horses were significantly thicker compared to their own baseline values and compared to control horses. In conclusion, presumptive colon pathology was identified with a high incidence, starting early in the course of treatment, but with low severity. Appropriate monitoring should be advised throughout NSAID treatment. Additional research for noninvasive diagnostic tests for colon pathology is required.

Added value of hyperdense lumen sign in prediction of acute central and peripheral pulmonary embolism on non-contrast CT chest

BackgroundPulmonary embolism (PE) is a common condition with considerable morbidity and mortality; it is more often diagnosed post-mortem by pathologists than in vivo by clinicians. Prompt and accurate diagnosis is difficult because PE may be clinically silent, the symptoms are vague and nonspecific, and in addition, there is no definitive, non-invasive diagnostic test to establish its diagnosis. The aim of this study is to assess the reliability of detection of acute central and peripheral pulmonary embolism (PE) on non-contrast CT especially when no possible alternative is available as in allergic cases or emergency, patients with history of renal disease, or in cases where PE is not the leading diagnosis. CT pulmonary angiography study served as our gold standard.ResultsEighty adult patients were included in our study; 44 were females and 36 males most of which were complaining of dyspnea and chest pain. Acute central pulmonary embolism was confirmed by CTPA. They all underwent a pre-contrast study just prior to the CTPA. Presence of high attenuation emboli in any of the main pulmonary vessels was our key for diagnosis of acute embolism. Non-contrast CT chest diagnosed 26 of the 47 cases confirmed by CTPA. The hyperdense lumen sign had an overall sensitivity of 55.3%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value of 61.1%. The accuracy of non-contrast CT chest study was evaluated using CTPA as our gold standard.ConclusionNon-contrast CT chest is a good indicator in predicting central and peripheral pulmonary embolism, particularly in cases of emergency, those unable to take intravenous contrast for angiography, or in cases where pulmonary embolism is not the leading diagnosis.

Automated Detection of Multiple Sclerosis Lesions in Normal Appearing White Matter from Brain MRI – A Survey

Multiple Sclerosis is an inoperable disease of the Central Nervous System (CNS) that irritates the myelin sheath by forming lesions. This affects all organs of the CNS; the vital of them is the brain. This disease can be detected by diagnosis like Magnetic Resonance Imaging (MRI). It is a non-invasive diagnostic test that provides detailed images of the soft tissues of the body. Out of the different variations of MRI, MS lesions are predominantly visible in the DTI (Diffusion Tensor Imaging) variant of MRI. DTI gives enhanced visualization of normal-appearing white matter tracts of the organs, hence providing a better image of the MS lesion. In this paper, the latest methodologies regarding the identification of the MS lesions in MRI scans like T2 FLAIR or DTI, using automated techniques like deep learning, computer vision, neural network and many more are surveyed. Furthermore, this paper consists of a proposed model which would focus on correlating the lesions found in DTI scan with the basic MRI scan like T2. It would identify the MS lesion in DTI scan and eventually highlight that lesion position in the T2 image scan. This would help radiologist in a way to effectively handle multiple MRI scans.

Non-Invasive Infections Diagnosis in Lung Transplant Recipients in Exhaled Breath Condensate

Purpose The purpose of this research was to identify diagnostic volatile organic compounds (VOCs) in exhaled breath condensate (EBC) from lung transplant recipients (LTR) colonized or infected by Aspergillus spp., Staphylococcus aureus and Pseudomonas aeruginosa, in order to develop a cheap, accurate and quick non-invasive diagnostic test. To this end we performed metabolomic analysis in EBC using gas chromatography-time-of-flight mass spectrometry (GC-QTOF) in the high-resolution mode. Methods Between January 2018-June 2019, 40 LTR were recruited in the Lung Transplant Unit, from whom 71 EBC and respiratory samples (sputum, bronchoalveolar lavage or oropharyngeal swabs) were obtained. Bacteria and fungi identification were performed according to routine laboratory standards for respiratory samples. The ECOScreen2 device was used for EBC collection at -20 °C during 15 minutes, and samples were stored at −80°C in 200 μL and 500 μL aliquots until analysis. EBC samples from patients colonized either with P. aeruginosa, S. aureus, Aspergillus spp. or none of the above (controls) where selected for headspace Solid Phase Micro Extraction (SPME) with DVBP fibres in order to concentrate VOCs before their injection in the Agilent GCMS 7200 Accurate Mass Q-TOF equipment for the metabolomic analysis. GC-QTOF untargeted analysis (deconvolution, alignment, and recursive analysis) was performed with the MassHunter and Mass Profiler Software, and statistical analysis with R software. Results We selected 27 samples for SPME-GC/QTOF analysis: nine controls, seven from patients colonized by Aspergillus spp., six with P. aeruginosa, three with S. aureus and two with both P. aeruginosa and S. aureus. The PLS-DA analysis clearly differentiated patients colonized with S. aureus or P. aeuruginosa from those who were not, with a very little overlap in patients colonized with A. fumigatus from the controls. Volcano plot analysis found two possible biomarkers for Aspergillus spp. detection, six for S. aureus and none for P. aeruginosa, may be because of the small n in our study. Conclusion SPME-GC/QTOF in EBC is a promising tool for non-invasive diagnosis of fungal and bacterial infections in LTR. However, the presumptive identification of these biomarkers needs to be confirmed with targeted metabolomic studies and their sensitivity and specificity should be studied in future research.

Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles.

Diagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment. Here we describe proof of concept for a novel urine diagnostics for TE using Poly-N-Isopropylacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic. Our results demonstrate nanoparticle technology's potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.

60941 Vaginal pH predicts cervical intraepithelial neoplasia-2 regression in women living with human immunodeficiency virus

ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.

Non-Invasive Colorimetric Magneto Loop-Mediated Isothermal Amplification (CM-LAMP) Method for Helicobacter pylori Detection.

More than half the world's population is thought to be infected with Helicobacter pylori. Although the majority of infected people are asymptomatic, H. pylori infection may cause gastric ulcers and deadly gastric cancer. Owing to the difficulty and invasiveness of current routine culture and diagnostic methods, a highly sensitive and specific noninvasive assay for H. pylori is of interest. This study highlighted the design and performance of a colorimetric magneto loop-mediated isothermal amplification (CM-LAMP) assay to detect H. pylori in spiked saliva samples. LF primers were coated on magnetic nanoparticles by carbodiimide-induced immobilization and functionally used for solidphase amplification. During the LAMP reaction at 66°C, biotin-tagged FIPs were incorporated into LAMP amplicons. The colorimetric signal developed after the addition of NeutrAvidin horseradish peroxidase conjugate (NA-HRP) and ABTS. None of the tested microorganisms, including closely related bacteria, was shown positive by the CM-LAMP assay except H. pylori isolates. This novel platform was highly specific and 100-fold more sensitive (40 CFU/ml or 0.2 CFU per reaction) than the PCR and conventional LAMP assays for the detection of H. pylori in spiked saliva. Our results demonstrated the feasibility of using this noninvasive molecular diagnostic test to detect H. pylori in saliva samples.

Clinical judgement in chest pain: a case report\xa0

BackgroundCardiac stress testing is a validated diagnostic tool to assess symptomatic patients with intermediate pretest probability of coronary artery disease (CAD). However, in some cases, the cardiac stress test may provide inconclusive results and the decision for further workup typically depends on the clinical judgement of the physician. These decisions can greatly affect patient outcomes.Case presentationWe present an interesting case of a 54-year-old Caucasian male with history of tobacco use and gastroesophageal reflux disease (GERD) who presented with atypical chest pain. He had an asymptomatic electrocardiogram (EKG) stress test with intermediate probability of ischemia. Further workup with coronary computed tomography angiography (CCTA) and cardiac catheterization revealed multivessel CAD requiring a bypass surgery. In this case, the patient only had a history of tobacco use but no other significant comorbidities. He was clinically stable during his hospital stay and his testing was anticipated to be negative. However to complete workup, cardiology recommended anatomical testing with CCTA given the indeterminate EKG stress test results but the results of significant stenosis were surprising with the patient eventually requiring coronary artery bypass grafting (CABG).ConclusionAs a result of the availability of multiple noninvasive diagnostic tests with almost similar sensitivities for CAD, physicians often face this dilemma of choosing the right test for optimal evaluation of chest pain in patients with intermediate pretest probability of CAD. Optimal test selection requires an individualized patient approach. Our experience with this case emphasizes the role of history taking, clinical judgement, and the risk/benefit ratio in deciding further workup when faced with inconclusive stress test results. Physicians should have a lower threshold for further workup of patients with inconclusive or even negative stress test results because of the diagnostic limitations of the test. Instead, utilizing a different, anatomical test may be more valuable. Specifically, the case established the usefulness of CCTA in cases such as this where other CAD diagnostic testing is indeterminate.

Cardiac care of Non-COVID-19 patients during the SARS-CoV-2 pandemic: The pivotal role of CCTA

Funding AcknowledgementsType of funding sources: None.AimsTo describe the role of coronary CT angiography (CCTA) as the sole available non-invasive diagnostic test for symptomatic patients with suspected CAD in a hub center for cardiovascular emergencies in the presence of limited access to hospital facilities during the COVID-19 pandemic. Methods and ResultsFrom March 9th to April 30th, during the peak of the COVID-19 pandemic, a consecutive cohort of symptomatic patients with high clinical suspicion of CAD and clinical indication to CCTA were enrolled in a hub hospital in Milan, Italy. When obstructive coronary artery disease was detected (>70% diameter stenosis in a proximal coronary segment or >90% stenosis in any coronary segment) patients were referred to invasive coronary angiography (ICA). Clinical follow-up was assessed in patients in whom ICA was considered deferrable.Overall, 58 consecutive patients were included. Ten (17.2%) symptomatic patients underwent ICA according to CCTA findings, while in 48 (82.8%) patients ICA was deferred. No clinical events were recorded after a mean follow-up of 49.7 ± 16.8 days. In nine out of ten patients referred to ICA, severe coronary artery disease was confirmed and treated accordingly. Changes in medical therapy were significantly more prevalent in patients with vs. those without CAD at CCTA.ConclusionWe report a potential pivotal role for CCTA in the triage of non-COVID-19 patients with suspected CAD during the SARS-CoV-2 pandemic. CCTA may be helpful for identifying patients who necessitate ICA, ensuring adequate resource utilization during the pandemic.

Predicting cardiac disease from interactions of simultaneously-acquired hemodynamic and cardiac signals

Background and ObjectiveCoronary artery disease (CAD) and heart failure are the most common cardiovascular diseases. Non-invasive diagnostic testing for CAD requires radiation, heart rate acceleration, and imaging infrastructure. Early detection of left ventricular dysfunction is critical in heart failure management, the best measure of which is an elevated left ventricular end-diastolic pressure (LVEDP) that can only be measured using invasive cardiac catheterization. There exists a need for non-invasive, safe, and fast diagnostic testing for CAD and elevated LVEDP. This research employs nonlinear dynamics to assess for significant CAD and elevated LVEDP using non-invasively acquired photoplethysmographic (PPG) and three-dimensional orthogonal voltage gradient (OVG) signals. PPG (variations of the blood volume perfusing the tissue) and OVG (mechano-electrical activity of the heart) signals represent the dynamics of the cardiovascular system. MethodsPPG and OVG were simultaneously acquired from two cohorts, (i) symptomatic subjects that underwent invasive cardiac catheterization, the gold standard test (408 CAD positive with stenosis≥ 70% and 186 with LVEDP≥ 20 mmHg) and (ii) asymptomatic healthy controls (676). A set of Poincaré-based synchrony features were developed to characterize the interactions between the OVG and PPG signals. The extracted features were employed to train machine learning models for CAD and LVEDP. Five-fold cross-validation was used and the best model was selected based on the average area under the receiver operating characteristic curve (AUC) across 100 runs, then assessed using a hold-out test set. ResultsThe Elastic Net model developed on the synchrony features can effectively classify CAD positive subjects from healthy controls with an average validation AUC=0.90±0.03 and an AUC= 0.89 on the test set. The developed model for LVEDP can discriminate subjects with elevated LVEDP from healthy controls with an average validation AUC=0.89±0.03 and an AUC=0.89 on the test set. The feature contributions results showed that the selection of a proper registration point for Poincaré analysis is essential for the development of predictive models for different disease targets. ConclusionsNonlinear features from simultaneously-acquired signals used as inputs to machine learning can assess CAD and LVEDP safely and accurately with an easy-to-use, portable device, utilized at the point-of-care without radiation, contrast, or patient preparation.

INFLAMMATORY BOWEL DISEASE CLASSIFICATION USING THE GUT MICROBIOME: A BENCHMARK OF MICROBIAL DATA ANALYSIS METHODS

The prevalence of inflammatory bowel disease (IBD) is increasing throughout the developed world. For the newly diagnosed, the time between the appearance of symptoms and diagnosis can take months, involving invasive procedures. There is an urgent need to develop a simple, low cost, accurate and non-invasive diagnostic test.

INFLAMMATORY BOWEL DISEASE CLASSIFICATION USING THE GUT MICROBIOME: A BENCHMARK OF MICROBIAL DATA ANALYSIS METHODS

Abstract The prevalence of inflammatory bowel disease (IBD) is increasing throughout the developed world. For the newly diagnosed, the time between the appearance of symptoms and diagnosis can take months, involving invasive procedures. There is an urgent need to develop a simple, low cost, accurate and non-invasive diagnostic test. With decreasing costs of next-generation sequencing, many studies have compared IBD gut microbiomes to healthy controls, successfully identifying bacterial biomarkers for IBD. Unfortunately, a majority of these studies utilize machine learning and statistical methods on either single or low-sample size datasets. This results in the creation of disease classification models that have a high level of overfitting and therefore minimal clinical application to new patient cohorts. There are several data preprocessing methods available for data normalization and reduction of cohort specific signals (batch reduction) which can address this lack of cross-dataset performance. With an abundance of potential methods, there is a need to benchmark the performance and generalizability of various machine learning pipelines (combination of data preprocessing and model) for microbiome-based IBD diagnostic tools. We used a collection of 12 IBD-associated North American microbiome datasets (~4000 samples) to benchmark several machine learning pipelines. Raw sequencing data was processed, collapsed at the OTU or Genus level and merged using QIIME2. Datasets were then normalized using either sum-scaling or log based methods and batch reduction was performed using either zero-centering or Empirical Bayes’ approaches. Performance of pipelines was evaluated using binary accuracy, AUC, F1 metric and MCC score. Generalizability of pipelines was evaluated using leave one out cross validation, where data from one study was left out of the training set and tested upon. The best performing and most generalizable pipeline included a Random Forest model paired with centered log ratio based normalization and batch reduction via an Empirical Bayes’ based approach. This combination, along with others, showed equivalent or higher performance to that of more complex models involving deep neural networks (DNNs). In addition to benchmarking our pipelines, we also explore their limitations, such as the tendency of zero-centered batch reduction to rely on balanced data as input or the tendency of Empirical Bayes’ based methods to introduce artificial signals into data, evidencing certain methods as poor tools for clinical use. To our knowledge, this is the first comprehensive benchmark of data preprocessing and machine learning methods for microbiome-based disease classification of IBD. These findings will help improve the generalizability of machine learning models as we move towards non-invasive diagnostic and disease management tools for patients with IBD.

Diagnostic accuracy of Fusobacterium nucleatum IgA and IgG ELISA test in colorectal cancer

The colorectal cancer is a serious health problem. The diagnosis of the disease mostly relies on an invasive procedure. A non-invasive diagnostic test such as an immunoassay, may facilitate diagnosis of colorectal cancer. The purpose of the study was to evaluate the use of antibodies against Fusobacterium nucleatum in the diagnosis of colorectal cancer (CRC). Totally 78 patients in three groups were included in the study. F. nucleatum in the tissues was detected using quantitative polymerase chain reaction assay. F. nucleatum IgA and IgG were measured using enzyme linked immunosorbent assay. F. nucleatum was detected in 86.7% and 73.1% cases of CRC and precancerous-benign colon disease (P-BCD), respectively. The OD values from F. nucleatum IgA and IgG ELISA tests were higher in CRC group compared with healthy individuals. The sensitivity of IgA ELISA test varied between 31.8 and 95.5% depending on the chosen cut-off values. The positivity rate of antibodies in patients with high amount of F. nucleatum in tissue was significantly greater than in the negative group. The F. nucleatum IgA and IgG antibodies in CRC were higher than the ones in healthy controls but the discriminative ability of the ELISA test was not adequate to be considered as a diagnostic tool.

Surgical Management for a Broken Delivery Shaft in <i>Vivo</i> during PCI Following Acute Myocardial Infarction in a Complex LAD Artery Lesion: A Case Report and Literature Review

Stuck up and fracture of coronary angioplasty hardware are unwonted complications of percutaneous coronary interventions (PCI) for which surgical retrieval and management is once in a while required. We present one case of a 59-year-old diabetic, a hypertensive gentleman who attended the emergency room (ER) with central chest pain for 2 hours. After evaluation of the patient by physical and noninvasive diagnostic tests, he was diagnosed as a case of acute myocardial infarction (AMI) with stable hemodynamic. For the aforementioned findings, the patient was treated first with a thrombolytic agent in ER and then shifted to Cardiology Department for monitoring and further coronary evaluation by coronary angiography (CAG). CAG revealed essentially single vessel disease (SVD) with complex left anterior descending (LAD) artery lesion, so PCI was attempted but failed with an unfortunate incidence of the broken delivery shaft and left in vivo. Immediate decision making and surgical management for retrieval of lost angioplasty device and correction coronary lesion with revascularization save the patient from grave complication. All the series of events and management approaches of this very complex coronary artery lesion are discussed in this article.

Salivary Biomarkers of Oxidative Stress and Inflammation in Stroke Patients: From Basic Research to Clinical Practice.

Cerebral stroke is a serious worldwide health problem, as can be seen by the global epidemic of the disease. In this disorder, when the blood flow is compromised by ruptures or blocked arteries, sudden death of neurons is observed as a result of a lack of oxygen and nutrients. Numerous severe problems and frequent complications also exist in stroke patients; therefore, there is an urgent need to develop new therapeutic, diagnostic, and prognostic methods for the disease. At present, the diagnosis of stroke is based on a neurological examination, medical history, and neuroimaging, due to the fact that rapid and noninvasive diagnostic tests are unavailable. Nevertheless, oxidative stress and inflammation are considered key factors in stroke pathogenesis. Oxygen free radicals are responsible for oxidation of lipids, proteins, and DNA/RNA, which in turn contributes to oxidative damage of the brain. Toxic products of the oxidation reactions act cytostatically on the cell by damaging cell membranes and leading to neuronal death by apoptosis or necrosis. Thus, it seems that redox/inflammatory biomarkers might be used in the diagnosis of the disease. Nowadays, saliva is of increasing interest in clinical laboratory medicine. Redox biomarkers could be obtained easily, noninvasively, cheaply, and stress-free from saliva. This minireview is aimed at presenting the current knowledge concerning the use of salivary biomarkers of oxidative stress and inflammation in the diagnosis and prognosis of stroke.

Kartagener's syndrome in a young female: A rare diagnosis in a resource-limited facility

Kartagener's syndrome (KS) is a subset of a larger group of ciliary motility disorders called primary ciliary dyskinesia. It is a genetic disease with an autosomal recessive inheritance characterized by inefficient or absent mucociliary clearance. It is a very rare congenital malformation comprising a classical triad of situs inversus, bronchiectasis, and sinusitis. A 22-year-old single female Nigerian came to our health facility with complaints of recurrent productive, non-foul-smelling cough, nasal discharge, and occasional shortness of breath since early childhood. She had a positive history of recurrent hospital visitations and chronic use of antibiotics but with few hospitalizations for recurrent chest infection. Chest examination revealed a maximally audible apex beat on the right side of her chest. Chest radiograph showed dextrocardia, while a chest computer tomography scan revealed cystic and varicose bronchiectatic changes with peribronchial thickening and multiple tiny interstitial nodules, mainly in the bilateral middle and lower lung fields. The patient had a fair response on inhaled steroids, nasal steroid spray, antibiotics, mucolytics, and bronchodilators. She is on follow-up clinic visits and close monitoring for potential complications. Patients with KS exist in resource-poor settings like northern Nigeria, largely being managed as cases of chronic sinusitis, pneumonia, or asthma. Although there is no rapid, reliable, non-invasive diagnostic test for KS, accurate diagnosis is crucial if the risks of complications from advanced disease and reduced quality of life are to be averted.

Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD.

Lung cancer, chronic obstructive pulmonary disease (COPD) and asthma are inflammatory diseases that have risen worldwide, posing a major public health issue, encompassing not only physical and psychological morbidity and mortality, but also incurring significant societal costs. The leading cause of death worldwide by cancer is that of the lung, which, in large part, is a result of the disease often not being detected until a late stage. Although COPD and asthma are conditions with considerably lower mortality, they are extremely distressful to people and involve high healthcare overheads. Moreover, for these diseases, diagnostic methods are not only costly but are also invasive, thereby adding to people’s stress. It has been appreciated for many decades that the analysis of trace volatile organic compounds (VOCs) in exhaled breath could potentially provide cheaper, rapid, and non-invasive screening procedures to diagnose and monitor the above diseases of the lung. However, after decades of research associated with breath biomarker discovery, no breath VOC tests are clinically available. Reasons for this include the little consensus as to which breath volatiles (or pattern of volatiles) can be used to discriminate people with lung diseases, and our limited understanding of the biological origin of the identified VOCs. Lung disease diagnosis using breath VOCs is challenging. Nevertheless, the numerous studies of breath volatiles and lung disease provide guidance as to what volatiles need further investigation for use in differential diagnosis, highlight the urgent need for non-invasive clinical breath tests, illustrate the way forward for future studies, and provide significant guidance to achieve the goal of developing non-invasive diagnostic tests for lung disease. This review provides an overview of these issues from evaluating key studies that have been undertaken in the years 2010–2019, in order to present objective and comprehensive updated information that presents the progress that has been made in this field. The potential of this approach is highlighted, while strengths, weaknesses, opportunities, and threats are discussed. This review will be of interest to chemists, biologists, medical doctors and researchers involved in the development of analytical instruments for breath diagnosis.