Clinical Use For Detection Research Articles

Deciphering Phenotypes from Protein Biomarkers for Translational Research with PIPER.

Liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) has widespread clinical use for detection of inborn errors of metabolism, therapeutic drug monitoring, and numerous other applications. This technique detects proteolytic peptides as surrogates for protein biomarker expression, mutation, and post-translational modification in individual clinical assays and in cancer research with highly multiplexed quantitation across biological pathways. LC-MRM for protein biomarkers must be translated from multiplexed research-grade panels to clinical use. LC-MRM panels provide the capability to quantify clinical biomarkers and emerging protein markers to establish the context of tumor phenotypes that provide highly relevant supporting information. An application to visualize and communicate targeted proteomics data will empower translational researchers to move protein biomarker panels from discovery to clinical use. Therefore, we have developed a web-based tool for targeted proteomics that provides pathway-level evaluations of key biological drivers (e.g., EGFR signaling), signature scores (representing phenotypes) (e.g., EMT), and the ability to quantify specific drug targets across a sample cohort. This tool represents a framework for integrating summary information, decision algorithms, and risk scores to support Physician-Interpretable Phenotypic Evaluation in R (PIPER) that can be reused or repurposed by other labs to communicate and interpret their own biomarker panels.

Functional Near-Infrared Spectroscopy and Its Clinical Application in the Field of Neuroscience: Advances and Future Directions.

Similar to functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS) detects the changes of hemoglobin species inside the brain, but via differences in optical absorption. Within the near-infrared spectrum, light can penetrate biological tissues and be absorbed by chromophores, such as oxyhemoglobin and deoxyhemoglobin. What makes fNIRS more advantageous is its portability and potential for long-term monitoring. This paper reviews the basic mechanisms of fNIRS and its current clinical applications, the limitations toward more widespread clinical usage of fNIRS, and current efforts to improve the temporal and spatial resolution of fNIRS toward robust clinical usage within subjects. Oligochannel fNIRS is adequate for estimating global cerebral function and it has become an important tool in the critical care setting for evaluating cerebral oxygenation and autoregulation in patients with stroke and traumatic brain injury. When it comes to a more sophisticated utilization, spatial and temporal resolution becomes critical. Multichannel NIRS has improved the spatial resolution of fNIRS for brain mapping in certain task modalities, such as language mapping. However, averaging and group analysis are currently required, limiting its clinical use for monitoring and real-time event detection in individual subjects. Advances in signal processing have moved fNIRS toward individual clinical use for detecting certain types of seizures, assessing autonomic function and cortical spreading depression. However, its lack of accuracy and precision has been the major obstacle toward more sophisticated clinical use of fNIRS. The use of high-density whole head optode arrays, precise sensor locations relative to the head, anatomical co-registration, short-distance channels, and multi-dimensional signal processing can be combined to improve the sensitivity of fNIRS and increase its use as a wide-spread clinical tool for the robust assessment of brain function.

Optical coherence tomography and optical coherence tomography angiography in glaucoma: diagnosis, progression, and correlation with functional tests.

The present review will summarize the most updated findings with regards to optical coherence tomography and optical coherence tomography angiography in glaucoma, highlighting their clinical use for detection and monitoring of the disease, and their correlation to functional tests (such as visual field) widely employed in the asset of modern glaucoma clinics.

Decision support system for detection of hypertensive retinopathy using arteriovenous ratio.

Hypertensive Retinopathy (HR) caused by hypertension is a retinal disease which may leads to vision loss and blindness. Computer aided diagnostic systems for various diseases are being used in clinics but there is a need to develop an automated system that detects and grades HR disease. In this paper, an automated system is presented that detects and grades HR disease using Arteriovenous Ratio (AVR).The presented system includes three modules i.e. main component extraction, artery/vein (A/V) classification and finally AVR calculation and grading of HR. Proposed system uses vascular map and a set of hybrid features for A/V classification. The evaluation of proposed system is carried out using three datasets. The proposed system shows average accuracies of 95.14% for images of INSPIRE-AVR database, 96.82% for images of VICAVR database and 98.76% for local dataset AVRDB. These results support that the proposed system is trustworthy for clinical use in detection and grading of HR disease. Main contribution of proposed system is that it utilizes complete blood vessel map for A/V classification. These arteries and veins are then used to calculate AVR and grade HR cases based on AVR values. Another contribution of this article is that it presents a new dataset AVRDB for A/V classification and HR detection.

Procalcitonin--a Marker for Anastomotic Insufficiency after Pancreatoduodenectomy?

Anastomotic insufficiency after pancreatoduodenectomy (PD) represents a major complication in pancreatic surgery. Early detection and treatment of pancreatic fistulas (PF) are essential for the outcome of affected patients. Procalcitonin (PCT) is a biochemical marker which allows detection of bacterial infections. The aim of this study was to evaluate if PCT is suitable for early detection of PF after PD. In this prospective study patients undergoing PD from 08/2010 to 09/2012 were included into three groups: (1) patients without complications (n = 19), (2) patients with postoperative infections (n = 14) and (3) PF (n = 7). Using a defined study protocol, clinical (e.g., vital signs, drain fluid, etc.) and laboratory parameters (full blood count, inflammatory markers) were assessed daily for the first ten postoperative days. 76 patients were assessed. 40 (52.6%) patients underwent PD and were included. CRP and PCT demonstrated an initial peak at the 1st to 3rd postoperative day with subsequent normalization. Patients with postoperative infections and PF showed a significant increase of PCT and CRP (p < 0.05) compared to patients without complications. Leucocyte counts demonstrated a variance in all three groups and clinical use for detection of complications was not evident. Patients with a postoperative complication revealed significantly increased levels of PCT and CRP without the expected normalization. PCT and/or CRP did not enable a distinction between patients with PF or postoperative infections. Thus, PCT does not seem to be suitable for detecting PF after PD and its use in the postoperative course after PD cannot be recommended.

Comparative clinical evaluation of the IsoAmp® HSV Assay with ELVIS® HSV culture/ID/typing test system for the detection of herpes simplex virus in genital and oral lesions

BackgroundThe novel IsoAmp® HSV Assay employs isothermal helicase-dependent nucleic acid amplification and a user-friendly disposable test device to achieve rapid (<1.5h), on-demand qualitative detection of herpes simplex virus (HSV) types 1 and 2 in oral and genital lesions. ObjectivesTo compare performance of the IsoAmp® HSV Assay with the ELVIS® HSV ID/typing (shell-vial culture and DFA) test system for clinical specimens collected from oral and genital lesions in symptomatic patients. Study designA total of 994 specimens from male and female genital and oral lesions were obtained and evaluated at five study sites in the United States. Results from the IsoAmp® HSV Assay were compared to those from the ELVIS® system. Separate reproducibility studies were performed at 3 sites using a blinded and randomized study panel. Discrepant specimens were resolved by bidirectional sequencing analysis. ResultsAfter discrepant analysis, overall agreement of IsoAmp® with ELVIS® was 98.8% with 37.0% overall prevalence (all study sites). Reproducibility rates were well within expectations. ConclusionThe IsoAmp® HSV Assay showed excellent performance for clinical use for detection of HSV in genital and oral specimens. In contrast to ELVIS®, IsoAmp® HSV offers excellent sensitivity plus rapid on-demand testing and simpler specimen preparation.

Immunochromatographic IgG/IgM Test for Rapid Diagnosis of Active Tuberculosis

For rapid diagnosis and discrimination between active tuberculosis (TB) and other pulmonary diseases, we evaluated the clinical usefulness of detection of serum immunoglobulin IgG and IgM antibodies raised against mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens by a commercial rapid immunochromatographic IgG/IgM test (Standard Diagnostics, South Korea) in 246 serum samples from three groups of patients: (i) 171 patients with active TB (128 with pulmonary TB [pTB] and 43 with extrapulmonary TB [epTB]), (ii) 73 patients with pulmonary non-TB diseases, and (iii) two leprosy patients. The sensitivities of IgG and IgM in patients with active TB (pTB and epTB) were 68.4% and 2.3%, respectively. IgG had the best performance characteristics, with sensitivities of 78.1% and 39.5% in sera from patients with active pTB and epTB, respectively, and a specificity of 100%. The sensitivities of IgM were poor and were similar for pTB and epTB (2.3%). In contrast, specificity was very elevated (100%). The combination of IgG with IgM did not improve its sensitivity. IgG-mediated responses against the mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens might constitute a clinically useful tool for presumptive diagnosis and discrimination of active pTB from other pulmonary diseases. Moreover, based on its simplicity and rapidity of application, it could be a screening tool for active pTB in poorly equipped laboratories.

Evaluation of the diagnostic value of measuring IgG, IgM, and IgA antibodies to mycobacterial A60 antigen in active tuberculosis

The purpose of the present study was to evaluate the clinical usefulness of detection of serum immunoglobulin A (IgA), IgG, and IgM antibodies raised against the mycobacterial A60 antigen for the diagnosis and discrimination of active tuberculosis (TB) from other pulmonary diseases. Three commercially available ELISA kits (IgA, IgG, and IgM) (ANDA Biologicals, Strasbourg, France) were evaluated simultaneously in 246 serum samples from 3 groups of patients: group I, 171 patients with active TB (128 pulmonary TB and 43 extrapulmonary TB); group II, 73 patients with pulmonary non-TB diseases; and group III, 2 leprosies patients. The sensitivities of tests ranged from 31.3% (IgA) to 94% (IgG) in pulmonary TB patients and from 21% (IgA) to 84% (IgG) in extrapulmonary TB patients. The specificities of assays varied from 92% (IgG) to 96% (IgA) in the pulmonary non-TB group. Combination of IgG with IgA and/or IgM does not improve its sensitivity. Clinical use of the A60-based serodiagnostic IgG assay is of great value for the rapid diagnosis and discrimination between active TB and pulmonary non-TB diseases. Moreover, this test could be used to increase diagnostic accuracy, especially for smear-negative TB cases, which are difficult to diagnose.

Prostacyclin receptor stimulation facilitates detection of human platelet P2Y12 receptor inhibition by the PFA-100® system

The rationale for monitoring platelet inhibition by thienopyridines for the identification of patients at risk for future recurrent arterial thrombosis or ischemic events is intensively discussed, as well as which monitoring systems are appropriate, robust and reliable. Flow cytometric measurement of phosphorylated VASP (vasodilator-stimulated phosphoprotein), expressed as platelet reactivity index (PRI), is presently “the gold standard method” for evaluating P2Y12 receptor inhibition. The PFA-100® system, a commercially available and clinically widely used platelet test system, is based on a different principle, not that of VASP phosphorylation. The aim of the present study was to compare the two methods and evaluate whether the conventional PFA-100® collagen/ADP cartridge could be pharmacologically improved to enable its routine clinical use for detection of platelet P2Y12 receptor inhibition. The effects of increasing concentrations of the competitive P2Y12 receptor antagonist cangrelor (AR-C69931MX) and the time-dependent effects of a single oral loading dose of clopidogrel (600 mg) were analysed with human whole blood. P2Y12 receptor inhibition was measured by the VASP/PRI assay and the PFA-100® collagen/ADP cartridge system, with and without preincubation with the prostacyclin analog iloprost (Ilomedin®). In vitro addition of iloprost (0.5 nM) enabled PFA-100® collagen/ADP cartridge system detection of P2Y12 receptor inhibition in whole blood by cangrelor in vitro or by clopidogrel treatment of volunteers. The addition of a prostacyclin analog facilitates PFA-100® collagen/ADP system detection of P2Y12 receptor inhibition, achieving a sensitivity similar to that of the VASP/PRI reference method. Future studies should now evaluate whether this modified PFA-100® system, like the VASP assay, is a reliable test system for monitoring P2Y12 receptor inhibition under clinical conditions.

Evaluation of P-wave triggered signal-averaged electrocardiograms in healthy volunteers and discussion of useful clinical use for detection of patients with paroxysmal atrial fibrillation

Evaluation of P-wave triggered signal-averaged electrocardiograms in healthy volunteers and discussion of useful clinical use for detection of patients with paroxysmal atrial fibrillation

Validation of an Inexpensive B-Mode Ultrasound Device for Detection of Deep Vein Thrombosis

To validate a portable, inexpensive, real-time, B-mode ultrasound device compared with duplex ultrasound in the detection of proximal lower extremity deep vein thrombosis in hospitalized patients clinically suspected of having deep vein thrombosis. Prospective cohort study. Tertiary care community teaching hospital. Medical-surgical hospitalized patients undergoing duplex ultrasonography for clinically suspected lower extremity deep vein thrombosis. Hospitalized patients who underwent duplex ultrasound examinations were enrolled in the study. Blinded from the duplex ultrasound results, the investigators utilized the study ultrasound device to perform compression ultrasonography of the common femoral, superficial femoral, and popliteal veins within 48 h of the duplex examinations. The results of the study ultrasound device were recorded as normal (compressible) or abnormal (noncompressible). Of the 198 lower limbs evaluated, duplex ultrasonography documented 34 proximal lower extremity deep vein thrombi. The study ultrasound device detected 32 of the 34 proximal thrombi detected by duplex ultrasonography. One false-positive result of an examination occurred with the study ultrasound device. Compared with duplex ultrasonography, the study ultrasound device had a sensitivity of 94%, specificity of 99%, positive predictive value of 97%, and negative predictive value of 98%. The results of this investigation document that the study ultrasound device has an acceptable sensitivity, specificity, and diagnostic accuracy for clinical use in detection of proximal lower extremity deep vein thrombosis. Further evaluation and validation of this ultrasound device are warranted.

Phenotypic detection of mec A-positive staphylococcal blood stream isolates: High accuracy of simple disk diffusion tests

Detection of oxacillin-resistance in staphylococci by phenotypic methods remains problematic. Although standardized susceptibility test methods are adequate for Staphylococcus aureus, many are less satisfactory for the coagulase-negative staphylococci (CNS). We have studied 108 consecutive blood culture isolates of staphylococci. The mec A gene was detected by PCR in one S. aureus and 55 CNS isolates. Susceptibility testing was performed as follows: oxacillin (1-μg), ceftizoxime (30-μg), and cephalothin (30-μg) by disk diffusion; oxacillin, ceftizoxime, cephalothin, methicillin, ampicillin, ampicillin/sulbactam, penicillin, cefazolin, imipenem, and meropenem by the broth microdilution method. In addition, isolates were tested by the oxacillin agar screen plate method. The single oxacillin-resistant S. aureus strain was detected by all oxacillin susceptibility test methods and by the ceftizoxime disk and MIC methods. Two oxacillin-susceptible S. aureus were intermediate (minor error) by ceftizoxime broth microdilution (MIC, 16 μg/mL). The most sensitive, simple phenotypic methods for detection of oxacillin-resistant CNS ( mec A positive) were as follows: oxacillin disk diffusion at 98%, oxacillin screen plate at 91%, oxacillin broth microdilution at 87%, ceftizoxime disk diffusion at 100%, ceftizoxime broth microdilution at 87%, and methicillin broth microdilution at 83%. These results indicate that oxacillin and ceftizoxime disk diffusion tests are the most accurate phenotypic methods in routine clinical use for detection of oxacillin-resistant CNS. Oxacillin broth microdilution MIC testing (2% NaCl supplement) would perform more satisfactorily (100% sensitivity) with an adjusted interpretive breakpoint at ⩽0.5 μg/mL, in contrast to the lower accuracy of the “so-called” reference agar screen test.