When citrate ligands-capped gold nanoparticles are mixed with blood sera, a protein corona is formed on the nanoparticle surface due to the adsorption of various proteins in the blood to the ...nanoparticles. Using a two-step gold nanoparticle-enabled dynamic light scattering assay, we discovered that the amount of human immunoglobulin G (IgG) in the gold nanoparticle protein corona is increased in prostate cancer patients compared to noncancer controls. Two pilot studies conducted on blood serum samples collected at Florida Hospital and obtained from Prostate Cancer Biorespository Network (PCBN) revealed that the test has a 90–95% specificity and 50% sensitivity in detecting early stage prostate cancer, representing a significant improvement over the current PSA test. The increased amount of human IgG found in the protein corona is believed to be associated with the autoantibodies produced in cancer patients as part of the immunodefense against tumor. Proteomic analysis of the nanoparticle protein corona revealed molecular profile differences between cancer and noncancer serum samples. Autoantibodies and natural antibodies produced in cancer patients in response to tumorigenesis have been found and detected in the blood of many cancer types. The test may be applicable for early detection and risk assessment of a broad spectrum of cancer. This new blood test is simple, low cost, requires only a few drops of blood sample, and the results are obtained within minutes. The test is well suited for screening purpose. More extensive studies are being conducted to further evaluate and validate the clinical potential of the new test.
Objective: This work investigates the possibility of automated malaria parasite detection in thick blood smears with smartphones. Methods: We have developed the first deep learning method that can ...detect malaria parasites in thick blood smear images and can run on smartphones. Our method consists of two processing steps. First, we apply an intensity-based Iterative Global Minimum Screening (IGMS), which performs a fast screening of a thick smear image to find parasite candidates. Then, a customized Convolutional Neural Network (CNN) classifies each candidate as either parasite or background. Together with this paper, we make a dataset of 1819 thick smear images from 150 patients publicly available to the research community. We used this dataset to train and test our deep learning method, as described in this paper. Results: A patient-level five-fold cross-evaluation demonstrates the effectiveness of the customized CNN model in discriminating between positive (parasitic) and negative image patches in terms of the following performance indicators: accuracy (93.46% ± 0.32%), AUC (98.39% ± 0.18%), sensitivity (92.59% ± 1.27%), specificity (94.33% ± 1.25%), precision (94.25% ± 1.13%), and negative predictive value (92.74% ± 1.09%). High correlation coefficients (>0.98) between automatically detected parasites and ground truth, on both image level and patient level, demonstrate the practicality of our method. Conclusion: Promising results are obtained for parasite detection in thick blood smears for a smartphone application using deep learning methods. Significance: Automated parasite detection running on smartphones is a promising alternative to manual parasite counting for malaria diagnosis, especially in areas lacking experienced parasitologists.
BACKGROUND: Measurement of plasma fibrinogen is often required in critically ill patients or massively bleeding patients being resuscitated with colloid plasma expander. This study aimed at ...evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated significantly higher in plasma diluted with colloid plasma expander compared with isotonic saline.
STUDY DESIGN AND METHODS: Fibrinogen measurements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo‐optical Clauss methods, one mechanical Clauss method, a prothrombin‐derived method, and viscoelastic measurement through thromboelastometry.
RESULTS: Measurement of fibrinogen levels was significantly different when performed on alternate analytical platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo‐optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin.
CONCLUSION: This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss.
To provide a comprehensive overview of the complexities associated with cardiac troponin (cTn) testing. An emphasis is placed on the sources of error, organized into the preanalytical, analytical, ...and postanalytical phases of the testing pathway. Controversial areas are also explored.
A case scenario and review of the relevant literature describing laboratory considerations involving cTn testing are described.
Advanced comprehension of the specific assay used in a given laboratory is necessary for optimal reporting, utilization, and quality monitoring of cTn.
cTn assays are reliable diagnostic tests for acute myocardial infarction, but understanding their limitations is required for appropriate result interpretation.
Data regarding hematologic reference intervals (RI) for neonatal calves have not been published yet. The aims of this study were: a) to establish hematology RIs for neonatal Holstein calves, b) to ...compare them with the RIs for lactating cows, and c) to investigate the relationship of age and gender with the hematologic profile of calves. Two-hundred and fifty-four clinically healthy Holstein calves (1–9days old, from 30 farms) and 82 healthy Holstein cows (between 30 and 150days in milk, from 10 farms) were blood sampled once for a complete blood count evaluation, using the ADVIA 120 hematology analyzer. An additional blood sample was collected from each calf for serum total protein concentration measurement. RIs and age-related RIs were calculated with the Reference Value Advisor freeware. Comparisons between calves and cows and between male and female calves were performed with t-test or Mann-Whitney test. Red blood cell count (RBC), white blood cell count (WBC), neutrophil, lymphocyte and platelet counts in calves were higher, while mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were lower than in cows. Lymphocyte and platelets showed a notable increase through age. Finally, female calves had higher RBC, hematocrit and hemoglobin concentration than males. Age-specific RIs should be used for the interpretation of the complete blood count in Holstein calves.
•Hematology reference intervals in neonatal calves differ from those in adult cows.•Values recorded in calves of different breeds do not apply in Holstein calves.•Several hematologic analytes fluctuate during the early neonatal period.•Erythron parameters differ between male and female calves.
Detection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery can identify patients with minimal residual disease (MRD) who will ultimately recur. Most ctDNA MRD assays require ...tumor sequencing to identify tumor-derived mutations to facilitate ctDNA detection, requiring tumor and blood. We evaluated a plasma-only ctDNA assay integrating genomic and epigenomic cancer signatures to enable tumor-uninformed MRD detection.
A total of 252 prospective serial plasma specimens from 103 patients with colorectal cancer undergoing curative-intent surgery were analyzed and correlated with recurrence.
Of 103 patients, 84 stage I (9.5%), II (23.8%), III (47.6%), IV (19%) had evaluable plasma drawn after completion of definitive therapy, defined as surgery only (
= 39) or completion of adjuvant therapy (
= 45). In "landmark" plasma drawn 1-month (median, 31.5 days) after definitive therapy and >1 year follow-up, 15 patients had detectable ctDNA, and all 15 recurred positive predictive value (PPV), 100%; HR, 11.28 (
< 0.0001). Of 49 patients without detectable ctDNA at the landmark timepoint, 12 (24.5%) recurred. Landmark recurrence sensitivity and specificity were 55.6% and 100%. Incorporating serial longitudinal and surveillance (drawn within 4 months of recurrence) samples, sensitivity improved to 69% and 91%. Integrating epigenomic signatures increased sensitivity by 25%-36% versus genomic alterations alone. Notably, standard serum carcinoembryonic antigen levels did not predict recurrence HR, 1.84 (
= 0.18); PPV = 53.9%.
Plasma-only MRD detection demonstrated favorable sensitivity and specificity for recurrence, comparable with tumor-informed approaches. Integrating analysis of epigenomic and genomic alterations enhanced sensitivity. These findings support the potential clinical utility of plasma-only ctDNA MRD detection.
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Introduction
The gold standard for the determination of the erythrocyte sedimentation rate (ESR) is the Westergren method. Other methods to measure the ESR have become available. They range from ...modest modifications of the Westergren method to very different methodologies. The ICSH therefore established a Working Group to investigate these new approaches and compile recommendations for their validation and verification.
Methods
A panel of six experts in laboratory hematology examined the peer‐reviewed literature and EQA surveys from over 6000 laboratories on four continents performing ESR testing. This information was used to create lists of ESR instrument manufacturers and their methods.
Results
Only 28% of laboratories surveyed used the unmodified Westergren method, while 72% of sites used modified or alternate methods. Results obtained with the new instruments could differ from results obtained with the Westergren method by up to 142%. Different non‐Westergren methods showed differences from each other of up to 42%. The new methods were often significantly faster, safer, and less labor‐intensive. They reduced costs and often used standard EDTA tubes, eliminating the need for a dedicated ESR tube.
Conclusion
Based on the consensus of the Working Group, recommendations for manufacturers for the validation of new ESR methods were developed. In addition, a list of recommendations for laboratories that are moving to modified or alternate methods was compiled, addressing instrument performance verification and communications of results to clinical users.
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