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Attention - Please consider the following when assessing the literature regarding COVID-19 (SARS-CoV-2 infection)
COVID-19 is an emerging, rapidly evolving pandemic.
Available literature is changing quickly and studies summarised here may not represent the latest status of knowledge. Please consider that conclusions of articles of this list may be based on low sample numbers or manuscripts that are not peer-reviewed yet (pre-prints).
Hemocytometric characteristics of COVID-19 patients with and without cytokine Storm syndrome on the Sysmex XN-10 hematology analyzer.
A study on the haemocytometric characteristics of COVID-19 patients revealed that a cytokine-storm syndrome was associated with higher AS-LYMPH, RE-MONO and monocyte fluorescence.
Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection.
A retrospective analysis from four US hospitals associated an elevated red cell distribution width (RDW) at admission and an increasing RDW during hospitalisation with increased mortality risk in COVID-19 patients, and identified RDW as an independent mortality risk factor.
Reduced activity of B lymphocytes, recognised by Sysmex XN-2000™ haematology analyser, predicts mortality in patients with coronavirus disease 2019.
The antibody-synthesizing lymphocyte count (AS-LYMP#) together with age, C-reactive protein (CRP) and creatinine level was identified as an independent predictor of in-hospital mortality in COVID-19 patients.
Cell population data: Could a routine hematology analyzer aid in the differential diagnosis of COVID-19.
A letter to the editor that describes the detailed analysis of cell population data (CPD) from an XN-1000 in COVID-19 and non-COVID-19 patients. CBC parameters do not present with significant differences. The CPD parameters present with significant differences, with the most pronounced the elevated LY-WZ.
Complete blood counts and cell population data from Sysmex XN analyser in the detection of SARS-CoV-2 infection.
A letter to the editor that describes a categorisation of patients with infection/fever into distinct groups based on statistical analyses of complete blood count and cell population data (CPD) from an XN analyser. 93.5% of COVID-19 patients and 100% of non-COVID-19 patients were correctly classified. The authors suggested a flag for COVID-19 infection, based on the neutrophil-to-lymphocyte ratio (NLR) and CPD values.
Evaluation of Routine Blood Tests for Diagnosis of Suspected Coronavirus Disease 2019.
A descriptive diagnostic study that evaluated several routine blood tests for the diagnosis of COVID-19 at hospital admission. Lymphocytes, eosinophils, ferritin, LDH, D-dimer and hsCRP were included in the diagnostic criteria that identified suspected COVID-19 patients with a sensitivity of 91% and a specificity of 47%.
Immature platelets in patients hospitalized with Covid-19.
Patients with COVID-19 have increased immature platelets parameters (IPF, IPF#) compared to stable patients with cardiovascular risk factors. As the disease progresses IPF and IPF# are increased also compared to acute myocardial infarction patients.
A novel haemocytometric COVID-19 prognostic score developed and validated in an observational
multicentre European hospital-based study.
The intention of the prognostic score is to support the management of
COVID-19 patients. Score values generated within the first three days of hospital admission can predict clinical severity in COVID-19 patients over the next two weeks. The score performance was shown to be superior to single parameters or parameter ratios.
Rapid Screening of COVID-19 Patients by White Blood Cells Scattergrams, a Study on 381 Patients.
A specific pattern of WDF scattergram, the “sandglass shape” pattern of lymphocyte population, was investigated in a cohort of 381 patients and exhibited a sensitivity and specificity of 85.9% and 83.5% for identifying COVID-19 infection, respectively.
Temporal changes in immune blood cell parameters in COVID‐19 infection and recovery from severe infection.
The results show that CBC including extended parameters about activated lymphocytes may be a valuable tool to triage patients with COVID-19. AS-LYMP%L (as a percentage of lymphocytes) yielded the best area under the receiver operating characteristic curve for predicting severe disease.
High-fluorescent lymphocytes are increased in patients with COVID-19.
A retrospective analysis of patients from the epicentre of the COVID-19 outbreak in Wuhan, China showed that while lymphocyte (L) counts were progressively decreased as disease severity increased, high-fluorescent lymphocyte (HFL) count and HFL/L ratio were increased in mild and severe cases compared to healthy controls.
Decreased "WBC*LYM" was observed in SARS-CoV-2-infected patients from a fever clinic in Wuhan.
Retrospective CBC+DIFF data analysis from a fever clinic in Wuhan from February 2020 (mid-Corona-pandemic in China) to evaluate the diagnostic value of haematologic parameters in suspected COVID-19 patients. The combination parameter of WBC and LYM (WBC*LYM) showed the best performance data for the quick evaluation of the patients disease severity and whether the patient is likely to have COVID-19 or not.
A summary of the diagnostic and prognostic value of hemocytometry markers in COVID-19 patients.
Evaluation of Prognostic/Diagnostic Value of Hematological Markers in the Detection of Inflammation in Coronavirus Disease: A Review Study.
Single case reports
SARS-CoV-2: A New Aetiology for Atypical Lymphocytes.
COVID-19 and mycoplasma pneumoniae coinfection.
Plasmacytoid lymphocytes in SARS-CoV-2 infection (Covid-19).
Leukoerythroblastic Reaction in a Patient With COVID-19 Infection.
Evaluation of a confocal WSI scanner for FISH slide imaging and image analysis
A study on 14 FISH slides scanned with confocal and wide field microscopy on a 3D Histech Pannoramic Scanner System showed that confocal imaging provides sharper images. Confocal multi-layer scanning is supposed to be the future application tool for FISH imaging.
An Optimized Image Analysis Algorithm for Detecting Nuclear Signals in Digital Whole Slides for Histopathology
A new 3D Histech algorithm for image analysis optimized for whole slide quantification of nuclear immunostaining signals of ER, PR, and Ki-67 proteins in breast cancers was tested against two other open source applications. The new algorithm outcompeted the comparators for histopathological evaluation of breast cancer biomarkers in accurately detecting nuclear signals of predictive and prognostic biomarkers (ER, PR, Ki-67) as well as fluorescent DAPI labeled cell nuclei and higher processing speed.
An Optimized Image Analysis Algorithm for Detecting Nuclear Signals in Digital Whole Slides for Histopathology
A new 3D Histech algorithm for image analysis optimized for whole slide quantification of nuclear immunostaining signals of ER, PR, and Ki-67 proteins in breast cancers was tested against two other open source applications. The new algorithm outcompeted the comparators for histopathological evaluation of breast cancer biomarkers in accurately detecting nuclear signals of predictive and prognostic biomarkers (ER, PR, Ki-67) as well as fluorescent DAPI labeled cell nuclei and higher processing speed.
Construction and analysis of tissue microarrays in the era of digital pathology: a pilot study targeting CDX1 and CDX2 in a colon cancer cohort of 612 patients
Several investigated parameters indicate that CDX2 performs more robustly than CDX1 in terms of applicability. Our projected results show that (1) ngTMA is highly accurate and leads to a low frequency of tissue core loss, (2) different types of tumour heterogeneity can be investigated using the combined ngTMA-DIA workflow and (3) low percentages of CDX1 and CDX2 positive cells are associated with more aggressive tumour biology and the influence of different staining intensities on patient selection is much lesser in CDX2 than in CDX1.
Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis
During this investigation Tissue microarrays (TMA) were produced by using colorectal cancer (CRC) liver metastasis and patient-matched primary CRC. TMA covers every step of the digital TMA workflow from sample designation/slide preparation from the donor block to the final evaluation of the TMA project using TMA software solutions.
A Next-generation Tissue Microarray (ngTMA) Protocol for Biomarker Studies
“Tissue microarrays (TMA) are produced by repeated transfer of small tissue cores from a ‘donor’ block into a ‘recipient’ block and then used for a variety of biomarker applications. In this study a procedure using next-generation Tissue Microarrays (ngTMA) is decribed. ngTMA uses a protocol based on TMA planning and design, digital pathology and automated tissue microarraying. Due to its precision, flexibility and speed, ngTMA is a powerful tool to further improve the quality of TMAs used in clinical and translational research.”
A travel report of the implementation of virtual whole slide images in routine surgical pathology
This study provides an extensive overview about virtual microscopy and its implementation in the daily routine.
Validation of diagnostic accuracy using digital slides in routine histopathology
“Digital microscopy: a study designed to evaluate the scanning properties and digital slide based diagnostic accuracy. The study results reveal that digital slide based histopathological diagnoses can be highly coherent with those using optical microscopy, that the competency of pathologists is a factor more important than the quality of digital slide and that poor digital slide quality do not endanger patient safety as these errors are recognizable by the pathologist and further actions for correction could be taken.”
Automated high throughput whole slide imaging using area sensors, flash light illumination and solid state light engine
This article deals with the technical background and conclusion behind engineering decisions made during the development of 3DHISTECH's 3rd generation combined brightfield and fluorescent scanner. By applying the current camera technology and standard microscope optical components, a high throughput and high quality whole slide imaging is feasible which meets all demands for most of the routine diagnostic work.
Implementation of TMA and digitalization in routine diagnostics of breast pathology
This study demonstrates that in breast cancer routine diagnostics the application of Tissue microarrays (TMA) combined with digitalization of the stained multi-slides is more economical, less time consuming and therefore accompanied with a considerable cost reduction. In the daily diagnostics this tool also improves standardization of tumour profiling.
Faecal immunochemical test for colorectal cancer screening
Strong subsite-specific variation in detecting advanced adenomas by fecal immunochemical testing for haemoglobin
FOB-Gold was applied prior to colonoscopy by 3.466 participants of the German screening colonoscopy program. The goal was to proof the subsite specific sensitivity for various types of colorectal neoplasms by comparing FIT results with findings at screening colonoscopy. The iFOBT FOB-Gold showed a sensitivity of 95-100% and therefore an excellent performance in detecting CRC.
Real-Time Monitoring of Results During First Year of Dutch Colorectal Cancer Screening Program and Optimization by Altering Fecal Immunochemical Test Cut-Off Levels
Data were collected from the first year of the Dutch screening program (2014) with biennial FITs by real-time monitoring (529.056 people participating). Because of the higher than predicted positivity rate (10.6%) and the lower PPV (42.1%) after some months the FOB-Gold test cut-off was increased (from 15 to 47 µg Hb/g feces), resulting finally in 6.7% positivity rate and 49.1% PPV. It has been concluded that for optimization of screening performance (test cut-off adjustments) a close monitoring of the implementation program is needed.
Erasmus MC Rotterdam, NKI/Antoni van Leeuwenhoek COLORECTAL CANCER SCREENING PROGRAMME • Monitor 2014, 2015, 2016
RIVM commissioned Erasmus MC and the Netherlands Cancer Institute (NKI)/Antoni van Leeuwenhoek Hospital to carry out national monitoring of the CRC screening programme on an annual basis. Considering the first screening rounds in all 3 years participation rates (~71-73%) were quite similar. The same was valid for positivity and detection rates for advanced neoplasia (AN). During the second round in 2016 an increase in participation rate was visible and not unexpected, the positivity and detection rates and PPV decreased compared to the first round. This is based on the fact that the prevalence of AN normally decreases after the first rounds of screening.
Influence of sample return time and ambient temperature on the performance of an immuno-chemical faecal occult blood test with a new buffer for colorectal cancer screening
Investigation on the effects of sample return time and of season on the FOB-Gold performance with a new buffer (study included 20.371 participants from French SP). The positivity rates were 4.1, 4.1 and 4.6% for a sample return time of up to 3 days, 4-5 days and 6-7 days. At 20°C there was a decrease in Hb concentration of 5.1% after 7 days, at 30°C of 20.5%. As result at 20°C after 7 days 100% of the samples of participants with CRC (4/4) and 97% of samples of participants with advanced adenomas (38/39) remained positive. It was concluded that a delay in sample return and season did not affect the diagnostic yield of FOB-Gold.
A randomised comparison of two faecal immuno-chemical tests in population-based colorectal cancer screening
Comparison of two iFOBTs (FOB-Gold and OC-Sensor) on Dutch screening population (n=19.291; 60-74 years old). Both iFOBTs were equally acceptable to the participants. The test performance regarding detection of colorectal advanced neoplasia was comparable for both tests, as well as the positive predictive value. In conclusion, the OC-Sensor and FOB-Gold perform similar in population-based screening.
Fresh vs Frozen Samples and Ambient temperature have Little Effect on Detection of Colorectal Cancer or Adenomas by a Fecal Immunochemical Test in a Colorectal Cancer Screening Cohort in Germany
Comparison of detection of CRCs and colorectal neoplasms by FOB-Gold using fresh samples vs frozen samples and assessment of the influence of seasonal variations (temperatures) on test performance. 3.466 FIT sample results from the German colonoscopy screening program were assessed. 12.8% of frozen stool samples and 8.7% of fresh stool samples had positive results by FIT. After adjusting the test cut-off to achieve the same %age of positive results, both sample cohorts showed similar levels of sensitivity and specificity for colorectal neoplasms. In addition no differences in detection of neoplasms during different seasons (different outdoor temperatures) were observed. It has been concluded that the use of fresh vs frozen samples only slightly affected positivity rates at the recommended test cut-off.
SENTIFIT 270 SYSTEM CLINICAL PERFORMANCE EVALUATION COMPARED WITH OC SENSOR DIANA, FOR THE DETECTION OF HUMAN HAEMOGLOBIN AS FAECAL OCCULT BLOOD (FOB)
The study goal was to compare the clinical performances of SENTiFIT FOB-Gold (SENTiFIT270 system) with the OC-SENSOR DIANA system. A good concordance between the SENTiFIT and the DIANA assay was observed: SENTiFIT assay is a valid quantitative FIT.
Automated Faecal Imunoassay Testing (FIT) for Hemoglobin on a new dedicated analyzer
The SENTiFIT® 270 system with SENTiFIT® pierceTube for the quantitative determination of faecal occult blood was subjected to a performance evaluation based on CLSI standards. All of the manufacturer's data with respect to the analytical performance, linearity, prozone effect and reagent and calibration stability could be confirmed with a high accuracy.
SENTiFIT® - FOB Gold® latex Fecal Immunoassay Test (FIT) evaluation on SENTiFIT® 270 analyzer
The SENTiFIT® 270 system with SENTiFIT® pierceTube for the immunochemical quantitative determination of faecal occult blood was subjected to a performance evaluation based on CLSI standards. All of the manufacturer's data with respect to the analytical performance, linearity, prozone effect and reagent and calibration stability could be confirmed with a high accuracy. The system is user friendly and easy to use. The new, pierceable sample tube improves the measurement accuracy, reduces the input and leads to a complete automation of the FIT.
A new sampling device for faecal immuno-chemical testing: haemoglobin stability is still an open issue
Evaluation of the Hb stability in faeces collected with FOB-Gold Tube Screen and Tube NG that contain different buffers (buffer H, BH). 15 true positive samples were collected with both buffers, portioned and incubated at 4, 21 and 32°C for 10 days. Endpoint was the percentage of cumulative faecal Hb decrease (HbCD%). The results showed that no significant difference was visible between BH and BN in HbCD% at 4°C. At 21 and 32°C the HbCD% was lower in BH than in BN samples whereas no difference was found between samples stored in BH at 4 and 21°C.
SENTiFIT®-FOB Gold® latex Fecal Immunoassay Test (FIT) evaluation on SENTiFIT® 270 analyzer in CoreLab at the AUSL Modena Nuovo S.Agostino Estense hospital in Emilia Romagna Region
The aim of this study was to compare two quantitative FITs: SENTiFIT270 and OC-Sensor Diana. Both systems showed a high concordance (95.8%), sensitivity (100%) and specificity (95.2%).
. Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer
The objective target of this evaluation was to check the performance of the quantitative immunochemical test FOB-Gold and to propose a possible strategy for an organized screening programme. Result of this study: a one-sample strategy is preferred and with a recommended cut-off, the overall positivity rate would be manageable in EU countries.
Comparison between a guaiac and three immunochemical faecal occult blood tests in screening for colorectal cancer
The objective of this study was to evaluate a guaiac-based (G-) FOBT (Hemoccult-II) versus 3 immunochemical (I-)FOBTs (FOB-Gold, OC-Sensor, Magstream) within the French population-based organized screening programme. The study outcome reveals additional proof that I-FOBTs are superior to the selected G-FOBT whereas none of the 3 applied I-FOBTs pointed out any significant performance advantages towards the others.
Positivity rates and performances of immunochemical faecal occult blood tests at different cut-off levels within a colorectal cancer screening programme
The goal of this study was to investigate the following approaches: on the one hand a 2-sample strategy with at least one positive test and on the other hand a 1-sample strategy implying various cut-off values for one of the two I-FOBTs (FOB-Gold or OC-Sensor) performed in combination with a G-FOBT (Hemoccult-II). It turned out that using I-FOBTs, an acceptable strategy (for the French CRC screening programme) would be 2-day sampling with at least one positive test at a cut-off between 150-200 ng/mL (OC-Sensor) and 176-234 ng/mL (FOB-Gold).
Liquid biopsy in colorectal cancer
Prospective multicenter real-world RAS mutation comparison between OncoBEAM-based liquid biopsy and tissue analysis in metastatic colorectal cancer
This study represents the first prospective RAS mutation performance comparison providing a final concordance of 92% between plasma and tissue samples using the OncoBEAM™ RAS CRC assay (236 mCRC patients). This outcome reveals that the plasma-based OncoBEAM™ RAS CRC assay is a reliable opportunity to detect RAS mutations in order to decide about the rationale of applying anti-EGFR therapy.
Cross-platform comparison for the detection of RAS mutations in cfDNA (ddPCR Biorad detection assay, BEAMing assay, and NGS strategy)
This study compared the performance of the OncoBEAM™ RAS CRC IVD assay to ddPCR and NGS for the detection of KRAS/NRAS mutations in plasma from mCRC and NSCLC patients based of the analysis of paired blood and tissue samples. The OncoBEAM™ RAS CRC test revealed higher sensitivity than the two other technologies by testing cfDNA vs tissue analysis in mCRC and NSCLC samples (extended RAS panel) and enabled monitoring of somatic alterations in plasma-derived cfDNA.
Significance of Liquid Biopsy for Monitoring and Therapy Decision of Colorectal Cancer
This study monitored three mCRC patients who initially were RAS WT and demonstrate that follow-up using OncoBEAM RAS testing in plasma provides information about the clonal redistribution after discontinuation of anti-EGFR as well as emerging RAS mutations leading to resistance during anti-EGFR administration. On top of this it has been observed that RAS mutations can even develop in the absence of anti-EGFR therapy pressure.
Incorporating BEAMing technology as a liquid biopsy into clinical practice for the management of colorectal cancer patients: an expert taskforce review
BEAMing technology for the detection of mutated ctDNA in plasma based on international guideline-recommended expanded RAS testing offers the opportunity of rapid turnaround times, high sensitivity and standardization compared to conventional testing of tissue samples. The high degree of concordance between plasma OncoBEAM RAS testing versus standard tissue testing methods has been shown in several studies. BEAMing posseses the potential to replace tissue biopsy for the detection and monitoring of RAS mutations and enables precision and cost-effective CRC patient management by individualizing treatment plans.
Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in mCRC
“Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue. Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.”
Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients
RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement using the OncoBEAM™ RAS CRC assay. Monitoring of RAS ctDNA in patients RAS wt showed that OncoBEAM was useful to detect RAS mutations during anti-EGFR treatment. It was finally concluded that the high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients and that it is useful to monitor RAS in patients undergoing systemic therapy to detect potential treatment resistances.
Clinical validation of prospective liquid biopsy monitoring in patients with wild-type RAS metastatic colorectal cancer treated with FOLFIRI-cetuximab
”The current study provides evidences, obtained for the first time in an unbiased and prospective manner, that reinforces the utility of LqB for monitoring mCRC patients.”
Performance of Standardized BEAMing Platform for Detecting RAS Mutations in the Blood of Metastatic Colorectal Cancer (mCRC) Patients
“The high overall agreement of plasma and tissue RAS testing results (93.3%) demonstrates that blood-based OncoBEAMTM RAS CRC testing is a viable alternative to tissue-based RAS testing. Plasma RAS testing also provides an opportunity to monitor tumor RAS mutation dynamics during therapy in patients with systemic disease.”
Performance assessment of blood based RAS mutation testing: concordance of results obtained from prospectively collected samples
“The high overall agreement of plasma and tissue RAS testing results (92.2%) shows that OncoBEAMTM RAS CRC testing is a viable alternative to tissue-based testing in this prospective study. Analysis of discordants shows that differences between plasma and tissue RAS results may arise from tumour heterogeneity, disease evolution, low ctDNA shedding, or low tumour burden.”
Blood-based detection of RAS mutations to guide anti-EGFR therapy in colorectal cancer patients: Concordance of results from circulating tumor DNA and tissue-based RAS testing
”The high concordance of plasma and tissue results demonstrates that blood-based RAS mutation testing is a viable alternative to tissue-based RAS testing.”
Clonal Evolution and Resistance to EGFR Blockade in the Blood of Colorectal Cancer Patients
Liquid instead of tissue biopsy can be used to closely monitor the dynamic molecular evolution of metastatic colorectal tumors during anti-EGFR therapy in order to identify those patients that benefit from anti-EGFR.
Characterizing the patterns of clonal selection in circulating tumor DNA from patients with colorectal cancer refractory to anti-EGFR treatment
”Monitoring treatment-induced genetic alterations by sequencing ctDNA could identify biomarkers for treatment screening in anti-EGFR-refractory patients.”
Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial
BEAMing of circulating tumour DNA allowed the non-invasive analysis of tumour genotype in real time and the detection of tumour-associated mutations.
Blockade of EGFR and MEK Intercepts Heterogeneous Mechanisms of Acquired Resistance to Anti-EGFR Therapies in Colorectal Cancer
Liquid biopsies used for monitoring RAS mutations of mCRC patients on anti-EGFR therapy enable early initiation of combination therapies with MEK inhibitors in order to optimize the therapy success and delay disease progression.
Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
“…our results suggest that blood-based non-invasive monitoring of patients undergoing treatment with anti-EGFR therapies for the emergence of KRAS mutant clones could allow for the early initiation of combination therapies that may delay or prevent disease progression.”
Circulating mutant DNA to assess tumor dynamics
“We found that ctDNA measurements could be used to reliably monitor tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy. We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer.”
Lymph node analysis in colorectal cancer
Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study
Among all clinical and pathological parameters assessed in this study, only the OSNA outcome significantly affected survival of pStage II colorectal cancer patients, showing that OSNA positivity can be considered a risk-factor for recurrence in these patients.
Budget Impact Analysis of Molecular Lymph Node Staging Versus Conventional Histopathology Staging in Colorectal Carcinoma
Assessment of the budget impact in Spain by introduction of OSNA for lymph node analysis shows substantial savings when compared to standard node analysis. In addition, OSNA could lead a clinical benefit for colorectal cancer patients since a more accurate staging could be performed, thus avoiding unnecessary treatments.
Sentinel lymph node analysis in colorectal cancer patients using one-step nucleic acid amplification in combination with fluorescence and indocyanine green
In colorectal cancer patients, combination of ICG-NIR lymphangiography mapping and SLN analysis by OSNA can detect lymph node involvement, allowing more accurate staging and reducing the delay between surgery and adjuvant chemotherapy
Molecular analysis of sentinel lymph node in colon carcinomas by one-step nucleic acid amplification (OSNA) reduces time to adjuvant chemotherapy interval
Intraoperative analysis of SLNs by OSNA significantly reduces the time to adjuvant chemotherapy after surgery.
Intraoperative identification and analysis of lymph nodes at laparoscopic colorectal cancer surgery using fluorescence imaging combined with rapid OSNA pathological assessment
“OSNA can be combined with NIR and ICG lymphatic mapping to provide intraoperative assessment of nodal tissue in patients with colorectal cancer.”
Lymph node pooling: a feasible and efficient method of lymph node molecular staging in colorectal carcinoma
“LN pooling makes it possible to analyze a high number of LNs from surgical colectomies with few molecular tests per patient. This approach enables a feasible means to integrate LN molecular analysis from CC specimens into pathology diagnosis and provides a more accurate LN pathological staging with potential prognostic implications.”
Molecularly determined total tumour load in lymph nodes of stage I-II colon cancer patients correlates with high-risk factors. A multicentre prospective study
OSNA allows the identification of tumour burden (undetected by hystology) in lymph nodes of early colon cancer patients. Moreover, the Total Tumour Load (TTL) determined by OSNA correlates with high-risk factors and may be used for a better selection of stage I–II patients at risk of recurrence.
Endoscopic tattooing of early colon carcinoma enhances detection of lymph nodes most prone to harbor tumor burden
Endoscopic tattooing clearly improves identification of lymph nodes. Moreover, this method allows the detection of those lymph nodes most prone to carry tumor burden as demonstrated by the Total Tumour Load (TTL) values.
OSNA-Assisted Molecular Staging in Colorectal Cancer: A Prospective Multicenter Trial in Japan
High concordance between OSNA and histology. Besides, the TTL values determined by OSNA show to increase as the number of metastatic lymph node increases showing a trend compatible to the current pathological diagnosis system.
The diagnostic value of one-step nucleic acid amplification (OSNA) for sentinel lymph nodes in colon cancer patients
The OSNA method shows a performance comparable to multilevel fine pathological examination. Since it enables whole lymph node analysis, sampling bias can be avoided leading to a more accurate tumour staging.
Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study
More than 25% of initially pN0 patients were upstaged by OSNA suggesting that this standardized and accurate method may improve staging.
An optimal mRNA marker for OSNA (One-step nucleic acid amplification) based lymph node metastasis detection in colorectal cancer patients
A CK19 mRNA copy number cut-off of 75-500 copies/µl leads to a high sensitivity and specificity of the OSNA method.
Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?
The OSNA method shows comparable performance such as intensive histopathological evaluation and may lead to upstaging of more than 15% of colon cancer patients.
OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: results from a multicenter clinical performance study in Japan
OSNA can be considered a novel molecular examination tool for the staging of colon cancer patients.
One step nucleic acid amplification (OSNA) - a new method for lymph node staging in colorectal carcinomas
The OSNA method allows the rapid analysis of the whole node and can applied as tool to determine nodal status in colon cancer patients.
Lymph node analysis in lung cancer
Prognostic Significance of Lymph Node Examination by the OSNA Method in Lung Cancer Patients-Comparison with the Standard Histopathological Procedure
Lymph nodes are pooled in to 3-5 groups within a framework of a nodal zone and analysed by OSNA. In this setting, the authors proposed a higher nodal zone cut-off for OSNA of 615 copies.
Detection of lymph node metastasis in lung cancer patients using a one-step nucleic acid amplification assay: a single-centre prospective study.
The high sensitivity of OSNA enables detection of tumour cells missed by pathological examinations. These occult metastases may be the key to explaining why some patients classified as pN0 or pN1 after surgery are progressing with worse prognosis
Lymph node localisation in colorectal cancer
Ex vivo sentinel lymph node mapping in colorectal cancer using a magnetic nanoparticle tracer to improve staging accuracy: a pilot study
Based on 28 ex-vivo specimens of colorectal cancer, the authors concluded that ex vivo magnetic sentinel lymph node mapping with the Sentimag®/Sienna+® System is a feasible technique, which improves nodal staging accuracy.
Magnetic impalpable lesion localisation
Magseed – Safety and feasibility study of the use of magnetic marker seeds to localise breast cancers
Based on an initial experience in 29 breast cancer patients. All seed were detected and recovered without challenges. The author concluded, that Magseed is a safe and feasible device that offers accurate localisation and logistic enhancements.
Sentinel lymph node analysis in breast cancer
Total Tumor Load of mRNA Cytokeratin 19 in the Sentinel Lymph Node as a Predictive Value of Axillary Lymphadenectomy in Patients with Neoadjuvant Breast Cancer
OSNA is a highly sensitive, specific and reproducible diagnostic method applicable also for the analysis of sentinel lymph nodes after neo-adjuvant chemotherapy. Moreover, the Total Tumour Load assessed by OSNA can help predicting the probability of additional axillary metastases.
OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized open label trial
Standardising radiotherapy treatment of breast cancer patients with few metastatic lymph nodes is crucial due to the lack of consensus. The OPTIMAL study aims to demonstrate the non-inferiority of incidental irradiation compared to intentional irradiation of axillary nodes in terms of survival of breast cancer patients with limited involvement of sentinel lymph nodes according to OSNA.
Molecular analysis of sentinel lymph nodes in patients with breast cancer using one-step nucleic acid amplification (OSNA): Does not lead to overtreatment in the current era of de-escalating axillary management
Being a highly sensitive technique, OSNA detects more micrometastases in sentinel lymph nodes than standard histology but does not lead to overtreatment with more axillary dissections or irradiation.
One-step nucleic acid amplification CK19 copy number for sentinel node biopsy in breast cancer: Identification of new cutoffs to predict nonsentinel axillary node involvement
Among the different potential cut-offs for OSNA investigated, the Total Tumour Load (TTL) allowed the most accurate prediction of non-sentinel lymph nodes (SLN).
External validation of a prognostic model based on total tumor load of sentinel lymph node for early breast cancer patients
A nomogram based on total tumour load in the SLN determined by OSNA, age and the number of risk factors allows to predict probability of 5-year disease-free survival in breast cancer patients.
Sentinel node total tumour load as a predictive factor for non-sentinel node status in early breast cancer patients - The PORTTLE study
The Total Tumour Load (TTL) can predict metastatic non-sentinel lymph nodes and together with other patient and tumour features might support intra-operative decision on further axillary dissection.
One-step nucleic acid amplification can identify sentinel node-negative breast cancer patients with excellent prognosis
Patients treated with endocrine therapy alone and having negative SLN determined by OSNA show significantly better prognosis than patients pN0 by histology undergoing the same treatment.
Intraoperative Nomograms, Based on One-Step Nucleic Acid Amplification, for Prediction of Non-sentinel Node Metastasis and Four or More Axillary Node Metastases in Breast Cancer Patients with Sentinel Node Metastasis
An intraoperative nomogram including the Total Tumour Load (TTL) determined by OSNA can predict non-sentinel lymph node involvement and four or more axillary lymph node metastases. Such tool might support surgical and therapeutic decision-making.
Molecular Staging of Patients with Colon Cancer. The C-Closer-II Study: A Multicentre Study in Portugal
Molecular examination of lymph nodes by OSNA allows a more accurate staging of patients with colorectal cancer and standardizes nodal assessment. In this study, 28.8% of patients with histologically negative lymph nodes were found to have metastatic lymph nodes using OSNA
Intraoperative prediction of the two axillary lymph node macrometastases threshold in patients with breast cancer using a one-step nucleic acid cytokeratin-19 amplification assay
“OSNA identifies a TTL threshold value where, in the presence of involved SLNs, ALND may be avoided. This technique offers objective confidence in adopting conservative management of the axilla in patients with SLN macrometastases.”
Role of total tumour load of sentinel lymph node on survival in early breast cancer patients
“SLN TTL permits the differentiation between two patient groups in terms of DFS and OS, independently of axillary staging (pN), age and tumour characteristics (size, grade, lymphovascular invasion). This new data confirms the clinical value of low axillary involvement and could partially replace the information that staging of the entire axilla provides in patients on whom no axillary lymph node dissection is performed.”
A cut-off of 2150 cytokeratin 19 mRNA copy number in sentinel lymph node may be a powerful predictor of non-sentinel lymph node status in breast cancer patients
“Logistic regression models indicated that the cut-off of 2150 copies better discriminates patients with node negative or positive in comparison with the conventional OSNA cut-off (p<0.0001). This cut-off identifies false positive and false negative cases and true-positive and true negative cases very efficiently, and therefore better identifies which patients really need an ALND and which patients can avoid one. This is why we suggest that the negative cut-off should be raised from 250 to 2150. Furthermore, we propose that for patients with a copy number that ranges between 2150 and 5000, there should be a multidisciplinary discussion concerning the clinical and bio-morphological features of primary breast cancer before any decision is taken on whether to perform an ALND or not.”
Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase
”The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.”
Intraoperative molecular analysis of sentinel lymph nodes following neoadjuvant chemotherapy in patients with clinical node negative breast cancer: An institutional study
“The OSNA assay is a highly sensitive, specific and reproducible diagnostic technique that can be used to analyse SLNs following NAC. The total tumoral load may assist with predicting additional non SLN metastases.”
Intraoperative assessment of sentinel lymph node by one-step nucleic acid amplification in breast cancer patients after neoadjuvant treatment reduces the need for a second surgery for axillary lymph node dissection
The accurate and standardized intraoperative SLN analysis by OSNA decreases the need of a second surgery in 18.5% of breast cancer patients with a positive SLN after neoadjuvant therapy.
Clinical significance of breast cancer micrometastasis in the sentinel lymph node
The OSNA method shows the benefit of reproducibility among different institutions and the capability of analysing a whole lymph node in only 30-40 minutes.
One-step nucleic acid amplification assay for intraoperative prediction of advanced axillary lymph node metastases in breast cancer patients with sentinel lymph node metastasis
The Total Tumour Load (TTL) determined by OSNA analysis can predict further axillary lymph node metastases in breast cancer patients. The TTL can be assessed intra-operatively, thus it can be used during surgery to determine the need for axillary lymph node dissection.
The use of one-step nucleic acid amplification (OSNA) and tumour related factors in the treatment of axillary breast cancer: A predictive model
A predictive model combining Total Tumour Load (TTL) determined by OSNA analysis with lymphovascular invasion can identify breast cancer patients who require additional axillary treatment, i.e. axillary lymph node dissection or other adjuvant measures.
CK19 expression in breast tumours and lymph node metastasis after neoadjuvant therapy
The expression of CK19 protein is preserved after neoadjuvant therapy. This indicates that OSNA is a suited approach for lymph node analysis also upon neoadjuvant treatment.
A multiparametric predictive model of axillary status in patients with breast cancer: total tumoral load and molecular signature. A multicenter study
“The inclusion of PM in the multivariate model improved the AUC, especially when the total number of sentinel nodes were included. Differences were observed in the impact of the CTT among the different molecular profiles subtypes.”
Elaboration of a nomogram to predict non sentinel node status in breast cancer patients with positive sentinel node, intra-operatively assessed with one step nucleic acid amplification method
The nomogram described by Di Filippo et al. is a very useful tool for predicting non-SLN status in breast cancer patients with positive SLNs assessed intra-operatively by OSNA.
Tumoral load quantification of positive sentinel lymph nodes in breast cancer to predict more than two involved nodes
In this study, the OSNA result clearly correlates with the risk of having two or more metastatic non-SLNs in breast cancer patients.
Nomogram including the total tumoral load in the sentinel nodes assessed by one-step nucleic acid amplification as a new factor for predicting nonsentinel lymph node metastasis in breast cancer patients
The nomogram described by Rubio et al. incorporates the Total Tumour Load (TTL) assessed by OSNA and can be used to predict non-SLN positivity. This useful tool can support clinicians in decision-making.
A new clinical cut-off of cytokeratin 19 mRNA copy number in sentinel lymph node better identifies eligible for axillary lymph node dissection in breast cancer
The CK19 mRNA copy number represents a useful tool to predict the probability of nodal involvement and thus, it can be applied for the selection of patients in which axillary lymph node dissection could be recommended due to the high risk of further axillary lymph node metastases.
Using one-step nucleic acid amplification (OSNA) for intraoperative detection of lymph node metastasis in breast cancer patients avoids second surgery and accelerates initiation of adjuvant therapy
The intraoperative SLN analysis by OSNA reduces the need of a second surgery in breast cancer patients and allows a prompt initiation of adjuvant therapy.
Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay
Intraoperatively assessed Total Tumour load (TTL) in SLNs of clinically node negative breast cancer patients predicts for further non-SLN metastasis. TTL helps decision-making on performing or not axillary lymph node dissection.
Sentinel node tumour burden quantified based on cytokeratin 19 mRNA copy number predicts non-sentinel node metastases in breast cancer: molecular whole-node analysis of all removed nodes
The CK19 mRNA copy number determined by OSNA predicts non-SLN metastases. This study further support the predictive value of the OSNA result.
Molecular detection of lymph node metastasis in breast cancer patients treated with preoperative systemic chemotherapy: a prospective multicentre trial using the one-step nucleic acid amplification assay
“The OSNA assay can detect the residual tumour burden as accurately as conventional pathology, although chemotherapy-induced histological changes are present.”
Intraoperative sentinel node biopsy by one-step nucleic acid amplification (OSNA) avoids axillary lymphadenectomy in women with breast cancer treated with neoadjuvant chemotherapy
The OSNA result can predict the axillary status with a high accuracy also in clinically node negative patients at initial presentation who underwent neoadjuvant therapy.
Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients
The Total Tumour Load (TTL) determined by OSNA is an independent predictor of the nodal status and can support clinicians in personalising surgical treatment.
Clinical application of the one-step nucleic acid amplification method to detect sentinel lymph node metastasis in breast cancer
The OSNA assay allows the accurate analysis of SLN and the prediction of non-SLN metastases. Moreover, applying this technique reduces pathologist’s workload.
Intra-operative use of one-step nucleic acid amplification (OSNA) for detection of the tumor load of sentinel lymph nodes in breast cancer patients
OSNA is a very useful tool for supporting intra-operative decision-making about further axillary surgery, thus reducing the risk of second surgeries. Moreover, the CK19 copy number allows the prediction of further lymph node involvement and might help to find adequate adjuvant treatment options.
Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer
The CK19 mRNA copy number in the SLN is the most significant predictor of non-SLN involvement.
Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients
The OSNA method shows a higher sensitivity than intraoperative histological evaluation, and thus its use possibly leads to a decrease of the number of women who require a second surgical procedure for axillary lymph node dissection.
Intraoperative analysis of sentinel lymph nodes in breast cancer by one-step nucleic acid amplification
Cserni et al. describes in this review current literature and concerns related to the OSNA method.
Reliability of whole sentinel lymph node analysis by one-step nucleic acid amplification for intraoperative diagnosis of breast cancer metastases
Whole SLN analysis by OSNA provides objective and reproducible results that help treatment decision making and accurate characterisation of SLN staging.
Sentinel lymph node analysis in breast cancer: contribution of one-step nucleic acid amplification (OSNA)
The intraoperative analysis of SLN by OSNA enables the surgeon to perform, when necessary, axillary lymph node dissection during the same procedure.
Diagnosis of the sentinel lymph node in breast cancer: a reproducible molecular method: a multicentric Spanish study
OSNA is a very sensitive, specific and reproducible method that enables standardisation of the SLN diagnostic procedure.
Multicentre evaluation of intraoperative molecular analysis of sentinel lymph nodes in breast carcinoma
OSNA allows accurate intraoperative evaluation of SLN and show excellent concordance with histology. This promising approach will become the standard method for analysis of SLN and axillary LNs.
One-step nucleic acid amplification – a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group
OSNA is a reliable and standardized tool for the intraoperative detection of lymph node metastases and its adoption may lead to a benefit for the patients since unnecessary second surgeries are avoided.
Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer
OSNA enables whole lymph node analysis and therefore, sampling errors, which are related to histological techniques, are avoided. Moreover, the automated procedure leads to a high degree of standardization and objectivity.
One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients
CK19 mRNA copy number cut-off values enable to distinguish among macrometastasis, micrometastasis, and non-metastasis. The clinical findings indicate that the OSNA assay is a useful intraoperative detection method for the detection of lymph node metastasis in breast cancer patients.
Sentinel lymph node analysis in gastric cancer
Utility of the one-step nucleic acid amplification assay in sentinel node mapping for early gastric cancer patients
To perform minimized gastrectomies based on sentinel lymph node concept in early-stage gastric cancer patients, an accurate intraoperative diagnostic method such OSNA is essential. The outcome of this study shows OSNA’s utility in this setting.
One-step nucleic acid amplification (OSNA) for the application of sentinel node concept in gastric cancer
First performance evaluation study in gastric cancer in which lymph nodes were analysed by both H&E and OSNA. Results showed that OSNA is a highly sensitive and specific method in detecting nodal metastases and could be applied for the intraoperative diagnosis of sentinel lymph nodes in this cancer entity.
Sentinel lymph node analysis in gynaecological cancer
Diagnostic accuracy and economic impact of three work-up strategies identifying risk groups in endometrial cancer, fully incorporating sentinel lymph node algorithm
Accurate determination of pre-operative risk groups in endometrial cancer is crucial as well as agreement on a gold standard work-up strategy to be offered in every oncological center, including the role of sentinel lymph node and its most appropriate examination technique.
Standard ultra-staging compared to one-step nucleic acid amplification for the detection of sentinel lymph node metastasis in endometrial cancer patients: a retrospective cohort comparison
Higher detection rate of micrometastasis by OSNA when compared to ultra-staging, though both methods showed similar overall rate of sentinel lymph node positivity in endometrial cancer patients.
Role of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node low-volume metastasis in early-stage cervical cancer
Detection rate of micrometastasis with OSNA seems to be slightly higher than with ultra-staging/immunohistochemistry and may indicate a superior accuracy of molecular methods.
Accuracy of One-Step Nucleic Acid Amplification in detecting lymph Node metastases in endometrial cancer
OSNA appears to be a highly accurate tool for intraoperative assessment of sentinel lymph node in endometrial cancer.
Intra-operative assessment of sentinel lymph node status by one-step nucleic acid amplification assay (OSNA) in early endometrial cancer: a prospective study
Data shows correlation between the size of metastasis in the sentinel lymph node (SLN) and non-SLN positivity suggesting that the OSNA results could support surgical tailoring of early-stage EC patients for better risk stratification and individualisation of adjuvant therapy.
One-step nucleic acid amplification vs ultrastaging in the detection of sentinel lymph node metastasis in endometrial cancer patients
A combination of OSNA and SLNM approaches in endometrial cancer patients has great potential for the highly sensitive detection of metastatic lymph nodes as well as application of adjuvant therapy.
One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer
OSNA, together with SLNM could represent an efficient intraoperative tool for the selection of early stage endometrial cancer patients to be submitted for systematic lymphadenectomy.
One-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node metastasis in endometrial cancer
OSNA allows the analysis of the entire lymph node, thus it avoids missing metastases due to partial tissue analysis by standard H&E examination.
A new diagnostic method for rapid detection of lymph node metastases using a one-step nucleic acid amplification (OSNA) assay in endometrial cancer
The OSNA assay using CK19 mRNA is useful for the detection of lymph node metastases in endometrial cancer patients and in combination with SLN may facilitate individualised treatments.
Detection of sentinel lymph node metastases in cervical cancer: assessment of KRT19 mRNA in the one-step nucleic acid amplification (OSNA) method
OSNA can detect lymph node metastasis as accurately as conventional histopathology and may be an effective method for rapid intraoperative examination of sentinel lymph node in cervical cancer patients.
Sentinel lymph node localisation in prostate cancer
Magnetic Resonance Imaging of Sentinel Lymph Nodes Using Intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles in Prostate Cancer Patients: First-in-human Results.
The study in 50 patients with prostate cancer provided high sensitivity results in sentinel lypmph node biopsy with the Sentimag®/Sienna+® System and can be performed by an urologist alone.
Detection of CK19 mRNA Using One-step Nucleic Acid Amplification (OSNA) in Prostate Cancer: Preliminary Results
Pioneer study in prostate cancer showing that OSNA reliably detected CK-19 mRNA in tumor specimens. Results indicated that the promising usage of OSNA assay for the detection of lymph node metastases also in this cancer entity.
Sentinel lymph node surgery in prostate cancer using magnetic particles
In this review it was concluded that SPION-MRI, combined with a hand-held magnetometer (Sentimag), provides a nonradioactive technique for preoperative and intraoperative SLN localization. Compared with ePLND, sPLND provides increased diagnostic value and supports the individualized extension of PLND using sPLND in prostate cancer.
Magnetic Marking and Intraoperative Detection of Primary Draining Lymph Nodes in High-Risk Prostate Cancer Using Superparamagnetic Iron Oxide Nanoparticles: Additional Diagnostic Value?
By using the Sentimag®/Sienna+® System in 104 patients with prostate cancer, the authors demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sentinel lymph node biopsy, exceeding that of ePLND.
Sentinel lymph node dissection in prostate cancer using superparamagnetic particles of iron oxide: Early clinical experience.
Based on 20 patients with prostate cancer, the authors state, that the Sentimag®/Sienna+® method provides results comparable to radiotracer with the avoidance of radioactivity and preoperative imaging.
A novel method for intraoperative sentinel lymph node detection in prostate cancer patients using superparamagnetic iron oxide nanoparticles and a handheld magnetometer: the initial clinical experience.
First data of 20 patients with prostate cancer indicate that the sentinel lymph node biopsy with Sentimag®/Sienna+® is a simple, radiation-free, safe, feasible, and reliable method.
sentinel lymph node localisation in breast cancer
Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer
This study in 338 breast cancer patients showed that the use of SPIO is easy and can be performed by the surgeon alone. Detection rates in Sentinel Lymph Node Biopsy are comparable to the dual technique.
The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc99 and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies
“SPIO is an effective method for the detection of SN in patients with breast cancer. It is comparable to the standard technique and seems to simplify logistics.”
Use of a Magnetic Tracer for Sentinel Lymph Node Detection in Early-Stage Breast Cancer Patients: A Meta-analysis
Sentinel Lymph node detection with Sienna+® revealed non-inferior performance to the standard method in breast cancer patients with clinically node-negative status.
Sentinel lymph node identification using superparamagnetic iron oxide particles versus radioisotope: The French Sentimag feasibility trial
Sentinel lymph node detection with Sienna+ is seen as a feasible method and a promising alternative to radiotracer. A beneficial potential was identified for ambulatory surgery or sites without nuclear medicine departments.
The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment
Sentimag® was identified as safe with non-inferior performance compared to the radiotracer. The Sentimag® technique can be applied after a minimum learning curve. Especially when nuclear medicine units are not available, the magnetic detection provides an effective treatment of breast cancer patients.
The superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast cancer: A comparative non-inferiority study
This study showed non-inferiority of the Sentimag technique compared to radiotracer. Ex-vivo and intraoperative detection rates at the node level were found to be slightly higher with Sentimag.
The superparamagnetic iron oxide is equivalent to the Tc99 radiotracer method for identifying the sentinel lymph node in breast cancer
Detection of SLNs with SPIO was not inferior to radiotracer. Procedure is safe, reliable and facilitates patients and OR management.
The Central-European SentiMag study Sentinel lymph node biopsy with superparamagnetic iron oxide (SPIO) vs. radioisotope
“We obtained convincing results that magnetic SLNB can be performed easily, safely and equivalently well in comparison to the radiotracer method.”
Sentinel Node Biopsy Using a Magnetic Tracer Versus Standard Technique: The SentiMAG Multicentre Trial
Sentimag/Sienna+ is a feasible technique for SLNB. The identification rate is not inferior to the standard.
Performance Comparison of Sysmex Hematology Analyzers XN-550 and XN-10.
The XN-550 is highly reliable with functionality comparable to the XN-10. It has shown high correlation coefficients and excellent comparative performance in all CBC, DIFF and RET parameters (except BASO%). The overall flagging comparison was excellent among the XN-10, the XN-550 and the manual differential.
Reference intervals for a complete blood count on an automated haematology analyser Sysmex XN in healthy adults from the southern metropolitan area of Barcelona.
The aim of the study was to establish reference intervals for CBC, DIFF and reticulocytes for a Spanish population. Significant gender differences were found for RBC, PLT, HCT and HGB.
Establishing a Stand-Alone Laboratory Dedicated to the Care of Patients With Ebola Virus Disease.
The pocH-100i was used in a laboratory dedicated to detection of Ebola virus disease. Its accuracy was verified by comparison with the XE-2100 in the main laboratory, and its precision and reportable range were also consistent with Sysmex's claims.
Evaluation and optimization of the extended information process unit (E-IPU) validation module integrating the sysmex flag systems and the recommendations of the French-speaking cellular hematology group (GFHC).
Using the biomedical validation criteria, 21.3 % of samples triggered
a smear review. Modification of four criteria reduced the number of smears from 21.3 % to 15.0 % without loss of clinical value.
Performance evaluation of the Sysmex® XP-300 in an oncology setting: evaluation and comparison of hematological parameters with the Sysmex® XN-3000.
The XP-300 showed very good precision and linearity results, comparable with the XN-3000 analyser.
Performance evaluation of the new hematology analyzer Sysmex XN-series.
A good correlation was found between the XN-Series and XE-series for all parameters. The XN-Series dramatically reduced the smear rate (by 58%). Even at counts below 500/µL the XN provided an accurate WBC count using the Low WBC mode.
Technology and New Fluorescence Flow Cytometry Parameters in Hematological Analyzers.
This paper gives a good overview of the technology behind the XE-series and the benefits of flow cytometry and automatic cell counting. It shows that the XE-5000 delivers faster accurate results than older analysers.
Smear microscopy revision: propositions by the GFHC.
The GFHC reviewed in detail the criteria used within the CBC to generate blood smears and has decided on a number of minimum recommendations, defining threshold values and various situations in which the blood smear review is desirable.
Immature platelet fraction based diagnostic predictive scoring model for immune thrombocytopenia
The authors concluded that immature platelet fraction (IPF) could be a useful parameter to distinguish immune thrombocytopenia (ITP) from other causes of thrombocytopenia. They developed the predictive scoring model that could predict ITP with high probability.
Immature platelet fraction: A useful marker for identifying the cause of thrombocytopenia and predicting platelet recovery
The authors demonstrated that the IPF is an excellent marker for distinguishing hyperdestructive/consumptive from hypoproductive thrombocytopenia. Moreover IPF is a robust and reliable predictor of platelet recovery in patients with immune thrombocytopenia (ITP) and with malignancies undergoing chemotherapy.
Combined Immature Platelet Fraction and Schistocyte Count to Differentiate Pregnancy-Associated Thrombotic Thrombocytopenic Purpura from Severe Preeclampsia/Haemolysis, Elevated Liver Enzymes, and Low Platelet Syndrome (SPE/HELLP)
IPF and manual schistocyte counts were able to discriminate pregnancy-associated severe preeclampsia/haemolysis, elevated liver enzymes, and low platelet syndrome (SPE/HELLP) versus thrombotic thrombocytopenic purpura (TTP) patients. The model based on combination of parameters had a good predictive value to discriminate TTP from SPE/HELLP - sensitivity of 92.3%, specificity of 62.5% and AUC 0.827.
Reticulated platelets and immature platelet fraction: Clinical applications and method limitations
Thorough review about reticulated platelets and immature platelet fraction including overview of preanalytical and analytical limitations of methods and clinical applications.
Immature platelet fraction (IPF): A reliable tool to predict peripheral thrombocytopenia.
This retrospective study found that IPF higher than 13 % is predictive of peripheral thrombocytopenia. In isolated thrombocytopenia bone marrow aspiration could have been avoided in 66 % of patients in this study cohort.
A CBC algorithm combined with immature platelet fraction is able to identify JAK2 V617F mutation-positive polycythaemia vera patients.
The study proposes an algorithm based on CBC and IPF# parameters that allows to identify a cohort of high-likelihood polycythaemia vera (PV) patients and refer them for haematological review. IPF# > 20 ×109/L in combination with positive CBC criteria can identify JAK2 V617F mutation-positive PV patients.
The immature platelet fraction in hypertensive disease during pregnancy
This study shows that IPF% can be used to identify hypertensive diseases in pregnancy. Moreover, the absolute number of IPF and platelets could help to differentiate preeclampsia and HELLP syndrome.
Analytical performance of automated platelet counts and impact on platelet transfusion guidance in patients with acute leukemia.
In this study the performance of impedance platelet counting using PLT-I, LH-750 (PLT-LH), as well as PLT-F was analysed in patients with acute leukaemia. PLT-F demonstrated an excellent performance for the identification of thrombocytopenia and had the lowest rate of undertransfusion. Additionally, the authors found that a high blast count is associated with inaccurate PLT-LH and PLT-I counts.
Prognostic significance of reticulated platelet levels in diabetic patients with stable coronary artery disease.
In stable coronary artery disease patients with diabetes the increased levels of immature platelets (IPF) are associated with a higher risk of major adverse cardiovascular events and inversely correlated with the risk of bleeding.
Immature Platelets As a Predictor of Disease Severity and Mortality in Sepsis and Septic Shock - A Systematic Review
Based on nine studies the review highlighted that an increased number of immature platelets is associated with increase disease severity and mortality in patients with sepsis and septic shock.
Reticulated Platelets - Changing Focus from Basics to Outcomes.
The authors discussed the role of reticulated platelets in coronary artery disease and in hypo responsiveness to the commonly used anti-platelet drugs. Reticulated platelets may be a useful marker for predicting worse cardiovascular outcome.
Innovative haematological parameters for early diagnosis of sepsis in adult patients admitted in intensive care unit.
The combination of an increased value of IPF# and a decreased value of RET% 24 hours before the onset of sepsis in ICU patients may be considered an early, rapid, inexpensive and widely available measure of sepsis prediction.
Immature platelet fraction (IPF) as a predictive value for thrombopoietic recovery after allogeneic stem cell transplantation.
IPF was able to predict platelet recovery in patients after allogeneic haematopoietic stem cell transplantation in 5 out of 11 patients, while IPF# was able to predict recovery in 7 out of 11 patients. Cut-offs of 5.8 % and 200/µL were used, respectively.
Recurrent Cardiovascular Events Despite Antiplatelet Therapy in a Patient with Polycythemia Vera and Accelerated Platelet Turnover.
The case report illustrates that insufficient platelet inhibition with clopidogrel monotherapy in a patient with thrombocytosis may be associated with recurrent arterial thrombosis. A plausible explanation may be an accelerated platelet turnover reflected by an increased number of immature platelets.
Immature platelets as a novel biomarker for adverse cardiovascular events in patients after non-cardiac surgery.
IPF with optimal cut-off of > 5.4 % is an independent predictor of major adverse cardiovascular events, deep vein thrombosis or pulmonary embolism (modMACE) after non-cardiac surgery and improve risk stratification of surgical patients.
Evaluation of the immature platelet fraction contribute to the differential diagnosis of hereditary, immune and other acquired thrombocytopenias.
The authors evaluated the use of IPF in the differential diagnosis between ITP and hereditary macrothrombocytopenia (HM). The IPF values were higher in HM than in ITP as already demonstrated by other studies.
Platelet turnover predicts outcome after coronary intervention.
An elevated platelet turnover independently predicts major adverse cardiovascular events after percutaneous coronary intervention. The optimal cut-off value was at IPF = 3.35 %.
The immature platelet fraction: creating neonatal reference intervals and using these to categorize neonatal thrombocytopenias.
Neonatal reference intervals for IPF and IPF# were reported according to gestational age, and during the first 90 days after birth. Moreover, neonates with hyporegenerative thrombocytopenias had lower IPF and IPF# than neonates with consumptive ones.
Abnormal leukocyte scattergrams and immature platelet fraction on Sysmex XN-9000 analyzer: a new diagnostic tool for altered megakaryopoiesis?
This case report shows how a high IPF, combined with abnormal WNR, WDF and WPC scattergrams could be used as a marker of dysmegakaryopoiesis, and led to the diagnosis of MDS type 2-refractory anaemia with excess blasts (REAB-2) in a nine year-old girl.
Assessment of platelet activation and immature platelet fraction as predictors of platelet engraftment after hematopoietic stem cell transplantation.
The study showed that IPF (XE-2100) can be used to assess thrombopoietic recovery after stem cell transplantation. Patients in the cord blood group had a higher IPF than the peripheral blood group on day 56 and day 97 post-transplantation.
Thrombocytopenia and platelet transfusion in the neonate.
The review summarises the pathophysiology and current management (including platelet transfusion thresholds) of neonatal thrombocytopenia. Novel index score for bleeding risk in thrombocytopenic neonates is proposed (including IPF#).
Immature platelet fraction in hypertensive pregnancy.
IPF% measured on the XE-5000 in pregnant women suffering hypertensive disorders was higher than in control group (3.8, 2.4–5.1 %; 8.6, 5.8–10.6 %; 7.3, 4.2–10.2 %; p < 0.001 for control group, preeclampsia syndrome and non-proteinuric hypertension, resp.).
Absolute immature platelet count dynamics in diagnosing and monitoring the clinical course of thrombotic thrombocytopenic purpura.
The absolute IPF (from XE-5000) is useful to diagnose and to monitor the clinical course of therapeutic plasma exchange in TTP patients. Routine analysis of the absolute IPF is recommended for diagnosis and to better assess the need for adjustment of treatment.
Clinical significance of IPF% or RP% measurement in distinguishing primary immune thrombocytopenia from aplastic thrombocytopenic disorders.
IPF% from the XN-1000 and RP% obtained by immuno flow cytometry had a comparable diagnostic value for the distinction between controls, immune thrombocytopenia (due to platelet destruction) and aplastic thrombocytopenia.
Immature platelet fraction values predict recovery of platelet counts following liver transplantation.
IPF% value predict recovery of PLT counts after liver transplantation. PLT counts reached the pre-transplant levels at 3-4 days after the IPF% peak value.
Immature platelet fraction measurement is influenced by platelet size and is a useful parameter for discrimination of macrothrombocytopenia.
The IPF% values were about five times higher in May-Hegglin disorders (IPF 48.6 ± 1.9 %) and about twice as high in other macrothrombocytopenias (IPF 18.4 ± 2.1 %) than in ITP patients with similar platelet counts (IPF 9.2 ± 0.3 %).
Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia.
IPF% obtained from the XE-2100 was increased in immune thrombo-cytopenia patients but not in patients with haematological malignancies. Therefore, IPF% may be used to evaluate the thrombopoietic state of the bone marrow.
Assessment of immature platelet fraction and immature reticulocyte fraction as predictors of engraftment after hematopoietic stem cell transplantation.
Both IRF% and IPF% can be used to predict neutrophil and platelet recovery, respectively. Work was done on XE-5000.
Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia.
The IPF# demonstrated stronger correlation with acute bleeding score than platelet counts. The strongest correlation was seen for paediatric patients with platelet counts <30 x109/L. High IPF# was associated with low bleeding score.
Reference interval for immature platelet fraction on Sysmex XN hematology analyzer: a comparison study with Sysmex XE-2100.
Reference intervals for PLT, IPF% and IPF# were established on the XE- and XN-Series. It was found that the values measured on the XN were higher than on the XE-2100.
Association of Immature Platelets With Adverse Cardiovascular Outcomes.
IPF# (XE-2100) allows for stratification of patients with coronary artery disease in terms of risk for future adverse events. Patients with an IPF# level ≥ 7,632 /µL were more likely to experience an adverse event (hazard odds ratio: 4.65; p < 0.002).
Evaluation of the IPF as an indicator of PLT recovery in dengue patients.
IPF can be used to monitor the thrombocytopenia in patients with dengue fever. Furthermore, it can predict the recovery of PLT and so avoid unnecessary blood transfusions.
Immature platelet fraction analysis demonstrates a difference in thrombopoiesis between normotensive and preeclamptic pregnancies.
The study illustrates the potential utility of IPF as a parameter to distinguish between normotensive and preeclamptic pregnant women. The authors suggest that IPF is a far better parameter than MPV, which has previously been suggested for this purpose, and can distinguish between the two groups even at normal platelet counts.
Immature platelet fraction (IPF) measured on the Sysmex XN haemocytometer predicts thrombopoietic recovery after autologous stem cell transplantation.
"IPF is a promising predictor of platelet recovery in patients after autologous SCT." "The proposed cut-off value of 5.3% can theoretically be used to decide whether or not to give a platelet transfusion."
Measurement of the absolute immature platelet number reflects marrow production and is not impacted by platelet transfusion.
Absolute IPF is a good parameter to assess the megakaryocytic activity of the bone marrow in transfusion-dependent thrombocytopenic patients.
Low immature platelet fraction suggests decreased megakaryopoiesis in neonates with sepsis or necrotizing enterocolitis.
Low absolute IPF values during the course of neonatal sepsis/necrotising enterocolitis suggest suppression of megakaryopoietic activity.
Establishment of reference interval for immature platelet fraction.
The study provides reference intervals for PLT, IPF% and absolute IPF from more than 2,000 healthy individuals and from umbilical cord blood, according to the CLSI guideline. These results could be used as fundamental data for clinical use as well as future researches.
Reticulated platelets predict cardiovascular death in acute coronary syndrome patients. Insights from the AMI-Florence 2 Study.
Reticulated (immature) platelets may be independent predictors of cardiovascular death and may potentially be useful in improving risk stratification for acute coronary syndrome patients.
The immature platelet fraction: where is it now?
A clear and concise review of 53 original publications concerning the clinical value of IPF. The diagnostic and prognostic potential of IPF in various conditions, and also advantages and limitations of IPF are described.
The immature platelet fraction: an assessment of its application to a routine clinical laboratory.
The purpose of the review is to assess the suitability of the IPF%
as a routine test. Productivity rather than clinical value is discussed. Reference ranges are given.
In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation.
IPF% was higher in patients with ITP than the controls, reflecting the increased platelet production. Treatment with eltrombopag led to increased platelet counts, platelet size, and absolute IPF, but no significant change in IPF%.
Application of reticulated platelets to transfusion management during autologous stem cell transplantation.
Using IPF-rich platelet transfusions reduces the number of transfusions and bleedings after stem cell transplantation in paediatric patients.
Mechanism of thrombocytopenia in chronic hepatitis C as evaluated by the immature platelet fraction.
IPF% can support the differentiation between platelet destruction and bone marrow failure in hepatitis C patients.
Predictive value of immature reticulocyte and platelet fractions in hematopoietic recovery of allograft patients.
The immaturity fractions IPF and IRF offer an easy and early evaluation method of post-transplantational recovery of the bone marrow
Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia.
The absolute immature platelet count (IPF#) can be used to assess the effect of different treatments of immune thrombocytopenia and could in such cases be more useful than IPF%.
Immature Platelet Count: A Simple Parameter for Distinguishing Thrombocytopenia in pediatric acute lymphocytic leukemia from immune thrombocytopenia.
"Both IPF% and IPF# parameters should become a standard for evaluating the respective pathophysiology’s underlying both congenital and acquired thrombocytopenias."
High platelet turnover and reactivity in renal transplant recipients patients.
Renal transplant recipients showed significantly higher values of reticulated platelets (IPF) than healthy control subjects, especially in those not on aspirin treatment.
An elevated IPF% could be an additional hint for a mechanism involved in the increased cardiovascular risk profile of those patients.
The immature platelet fraction is a useful marker for predicting the timing of platelet recovery in patients with cancer after chemotherapy and hematopoietic stem cell transplantation.
An IPF% of above 10% is a useful marker for predicting the timing of platelet recovery after chemotherapy and haematopoietic stem cell transplantation and has the potential to facilitate optimal platelet transfusion.
Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopenia.
"If the IPF is high, thrombocytopenic neonates are likely to recover on their own."
Prognostic value of immature platelet fraction and plasma thrombopoietin in disseminated intravascular coagulation
The authors demonstrated that the IPF is an excellent marker for distinguishing hyperdestructive/consumptive from hypoproductive thrombocytopenia. Moreover IPF is a robust and reliable predictor of platelet recovery in patients with immune thrombocytopenia (ITP) and with malignancies undergoing chemotherapy.
Immature platelet fraction for prediction of platelet engraftment after allogeneic stem cell transplantation.
IPF counting can provide an accessible marker of engraftment after transplantation, especially of thrombopoietic activity.
A simple technique to determine thrombopoiesis level using immature platelet fraction (IPF).
The results show that the IPF reflects the pathology of thrombo¬cytopenic disorders (i.e. consumptive versus productive). Measurement of the IPF is useful for the differential diagnosis and analysis of platelet kinetics and significantly more so than the mean platelet volume (MPV).
Immature platelet fraction measurement: a future guide to platelet transfusion requirement after haematopoietic stem cell transplantation.
The automated IPF is a useful parameter in the clinical evaluation of the thrombocytopenic patient and has the potential to allow optimal transfusion of platelet concentrates.
A clinical evaluation of high fluorescent platelet fraction percentage in thrombocytopenia.
The IPF (here named HFPF for ‘high fluorescence platelet fraction’) was predictive in the evaluation of thrombocytopenia. An elevated IPF is found with increased platelet production, particularly associated with platelet destruction, and in disorders associated with decreased platelet production the IPF is normal.
Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia.
Automated IPF% measurement should become a standard parameter in evaluating the thrombocytopenic patient.
Performance Evaluation of Automated Impedance and Optical Fluorescence Platelet Counts Compared With International Reference Method in Patients With Thalassemia.
PLT-I, PLT-O and PLT-F in thalassaemia patients were compared with CD41/CD61 immune flow cytometry. PLT-O and PLT-F had better correlations with flow cytometry than PLT-I. PLT-F had a better specificity for detection of PTL counts below 100,000/µL.
The Sysmex XN-2000 Hematology Autoanalyzer Provides a Highly Accurate Platelet Count than the Former Sysmex XE-2100 System Based on Comparison with the CD41/CD61 Immunoplatelet Reference Method of Flow Cytometry.
PLT-F counts from the XN-Series were more accurate than PLT-O counts from the XE series when compared with the CD41/CD61 immunoplatelet reference method.
Accuracy of a New Platelet Count System (PLT-F) Depends on the Staining Property of Its Reagents.
The study showed that the PLT-F reagent labels intracellular structures within platelets and confirms previous findings that it strongly marks CD41/CD61-positive platelets.
Evaluating platelet counting on a new automated analyser.
The PLT-F channel of the XN-Series shows excellent precision and accuracy even in abnormal samples or samples with fragmented red cells, large platelets and low PLT counts when compared to the reference flow cytometric method.
Performance Evaluation of Platelet Counting by Novel Fluorescent Dye Staining in the XN-Series Automated Hematology Analyzers.
Compared to PLT-I and PLT-O counts, PLT-F had the best correlation with CD61-immunoplatelet counts. PLT-F counts were not affected by WBC fragments in two acute leukaemia patients or by RBC fragments and microcytes in a burn injury patient.
New fluorescent method (PLT-F) on Sysmex XN2000 hematology analyzer achieved higher accuracy
in low platelet counting.
The PLT-F method of the XN-2000 demonstrated excellent reproducibility in samples with low platelet counts. Therefore, it is recommended for making decisions about platelet transfusions.
Performance evaluation of the Sysmex haematology XN modular system.
The XN showed reduced sample turnaround time and reduced number of blood film reviews compared to the XE-2100 without loss of sensitivity and with more precise and accurate results for both platelets and low WBC counts.
The most accurate platelet count on the Sysmex XE-2100. Optical or impedance?
The accuracy of the XE-2100 platelet counting on chemotherapy samples with low counts is excellent when the switching algorithm is used. The optical count is not always the most accurate and the overriding of the algorithm is not good practice.
Semiquantitative, fully automated urine test strip analysis.
This study evaluated the analytical and diagnostic performance of the UC-3500 for the presence of glucose, protein, albumin, leukocyte esterase, and hemoglobin peroxidase activity and ordinal scale results in comparison to the analysis of urine sediments using the UF-5000 as well as in comparison to wet clinical chemistry using the Roche cobas® 8000. Especially for detection of glycosuria, proteinuria and albuminuria, a perfect agreement between the reflectance data of the UC-3500 and immunochemistry results has been obtained. This allows the UC-3500 to provide a high‐throughput first‐level screening method for urinalysis which acts as a reliable sieving system to reduce the workload for further validation methods. Especially the albumin measurement fulfills optimum criteria for trueness allowing a reliable, semiquantitative detection of albumin.
Quantitative urine test strip reading for leukocyte esterase and hemoglobin peroxidase.
This study investigates diagnostic accuracy of the Sysmex UC-3500 automated urine chemistry analyzer based that uses CMOS sensor technology for leukocyte esterase and hemoglobin peroxidase results. In addition, the influence of urinary dilution, haptoglobin, urinary pH and ascorbic acid on the test results has been assessed. In conclusion, CMOS technology allows to obtain high quality test strip results for assessing WBC and RBC in urine. Quantitative peroxidase and leukocyte esterase are complementary with flow cytometry and have an added value in urinalysis, which may form a basis for expert system development.
Sensitive albuminuria analysis using dye-binding based test strips.
Delanghe and colleagues investigated the potential of the CMOS sensor technology of the UC-3500 for obtaining quantitative albuminuria results in comparison to clinical wet chemistry using the cobas® 8000 immunochemistry analyser. For albumin, this study revealed a limit of detection of 5.5 mg/l, respecting limits for screening for albuminuria in patients at risk of CKD. A strong or good correlation between strip reflectance data and albuminuria creatinine, respectively, potentially allows quantification of albuminuria and ACR by dye-binding test strip.
Investigation of Atyp.C using UF-5000 flow cytometer in patients with a suspected diagnosis of urothelial carcinoma: a single-center study.
This study evaluated the predictive power of the UF-5000 research parameter ‘Atypical Cells’ for patients with a suspected diagnosis of urothelial carcinoma. In total, urinary specimens of 128 patients that were enrolled for urinary cytology analysis were included in this investigation and analysed on the UF-5000, aiming to evaluate its performance in identifying atypical or malignant urothelial cells. The UF-5000 findings were in agreement with cytopathology in 73 % of the investigated cases. Using follow-up histologic diagnosis of urothelial carcinoma with or without urinary tract cytology (UTCy) as a reference standard the sensitivity and specificity were calculated with 59 % and 82.1 %, respectively. This resulted in a positive predictive value of 75.0% and a negative predictive value of 68.8%. In conclusion, the ‘Atypical Cells’ parameter bears the potential of an accessory test for urothelial carcinomas in context of routine urinary diagnostics, that might help to identify high-risk patients that require more specific follow-up and medical treatment.
“Atypical Cell” Parameter in Automated Urine Analysis for the Diagnosis of Bladder Cancer: A Retrospective Pilot Study.
This study evaluated the application of the UF-5000 and its research parameter ‘Atypical Cell’ in supporting the diagnosis of bladder cancer in a retrospective manner in a heterogenous study population. With an acceptable sensitivity of 75 % and a specificity of 100 %, the UF-5000 demonstrated potential value for diagnostic decisions on follow-up cystoscopy for patients with low-risk non-muscle invasive bladder cancer (NMIBC). For patients with high-risk NMIBC, sensitivity and specificity values are lower, but comparable or even better, if compared to cytology. The authors thus revealed the potential to avoid invasive procedures on patient side and to save costs for unnecessary treatments. To further investigate and validate the presented findings, a prospective study is in preparation.
Atypical cells in Sysmex UN automated urine particle analyzer: a case report and pitfalls for future studies.
The UF-4000 automatically detected atypical cells in the urine specimen of a 73-year old individual with recurrent high-grade urothelial carcinoma in an outpatient setting, which was confirmed by manual microscopy, demonstrating the potential of the UF-Series to detect malignancies.
Preliminary evaluation of UF-5000 Body Fluid Mode for automated cerebrospinal fluid cell counting.
This study evaluated the body fluid mode of the UF-5000 for analysis of CSF in comparison to microscopy. The UF-5000 showed a high diagnostic accuracy for TNC, WBC and RBC counts, as well as high sensitivities and specificities and confirmed a low limit of detection for the RBCs. In conclusion, the UF-5000 body fluid mode offers rapid and accurate quantification of cells, including bacterial cells in CSF samples in clinically relevant concentration ranges, allowing the replacement of microscopy for CSF samples without abnormal cell counts or scattergrams.
General / Review
Progress in Automated Urinalysis.
This publication is a comprehensive review of the current status of automated urinalysis, highlighting the potential quantitative reading of urinary test strips using CMOS technology for albuminuria testing and the value of urinary flow cytometry for the differentiation of urinary microorganisms, screening for urinary tract infections and clinical decision support in a variety of nephrological and urological diseases. In addition, progress in automated urinary microscopy and the improved pathogen identification by MALDI-TOF mass spectrometry is reflected and an outlook into future technologies, such as laboratory-on-a-chip approaches, use of microfluids and mobile applications is given.
Cost analysis of the automated examination of urine with the Sysmex UN-SeriesTM in a Spanish population.
This study aimed to investigate the potential of the Sysmex UN-Series to reduce high financial costs and high and time-consuming laboratory workloads of current urinalysis practice. By investigating more than 90,000 handled urine samples of a 10-year period, including financial data and alternative costs of reference and test scenarios, potential average cost savings of 340,000 € per year was identified for the use of automated urine examination, compared to the current urinalysis practice. On top, the UN-Series has the potential to reduce the annual working hours of laboratory personnel to up to 1615 hours. In conclusion, the implementation of the UN-Series within routine practice in clinical laboratories could minimise costs, provide substantial savings for investment, improve laboratory procedures and could contribute to synergy between clinical analysis and microbiology laboratories.
Renal Tubular Epithelial Cells Add Value in the Diagnosis of Upper Urinary Tract Pathology.
Oyaert and colleagues evaluated the analytical performance characteristics of renal tubular epithelial cells (RTECs) and transitional epithelial cells (TECs) on the Sysmex UF-5000 urine sediment analyser, as well as the diagnostic performance of these parameters to differentiate between lower and upper UTI. In comparison to transitional epithelial cells (TEC), increased urinary levels of renal tubular epithelial cells (RTEC) demonstrated a good potential to serve as a marker for the diagnosis of upper UTI and outperforms α1-micrglobulin in the discrimination between upper and lower UTI. However, the diagnostic performance of these parameters is strongly depending on proper sample handling.
Evaluation of the AID AmpC line probe assay for molecular detection of AmpC Enterobacterales.
This study investigated the use of commercially AID AmpC line probe assays for analysis of antibiotic resistance by detection of plasmid-mediated blaAmpC β-lactamase genes in Enterobacterales, which proofed to be an accurate, sensitive and easy-to-use test that can be readily implemented in any diagnostic laboratory. In this context, the UF-5000 has been demonstrated to be a reliable tool to judge samples, sent for molecular testing, for the presence of bacteriuria and to reduce the number of unnecessary molecular testing.
Compatibility of the Results of an Automated Urine Analyzer with Urine Culture.
This study evaluated the incidence of leukocyte esterase and nitrite positivity, leukocyte and bacterial counts in urine and Gram positive and negative bacterial results interpreted by the UF-5000 for compliance with urine culture results. Incorrect results for the Gram status in comparison to urine culture was obtained for three Gram-positive and three Gram-negative samples. Rates of leucocyte esterase, nitrite positivity, leukocyte and bacterial counts were higher in Gram negative group. In conclusion, especially Gram-negative bacterial interpretation obtained from the UF-5000 be beneficial for rapid typing of bacteria and early treatment in urinary tract infections.
Evaluation of the new Sysmex UF-5000 fluorescence flow cytometry analyser for ruling out bacterial urinary tract infection and for prediction of Gram-negative bacteria in urine cultures.
De Rosa and colleagues investigated the potential of the UF-5000 to rule-out urinary tract infections and its ability to predict the presence of Gram-negative bacteria in urine samples with a request for urine culture in context of a suspected urinary tract infection. With neglectable carry-over and cross-contamination, the UF-5000 demonstrated a high screening performance for urinary tract infections with a high sensitivity and NPV for the bacteria using a cut-off of ≥58/μl. The ‘Gran Neg?’ flag predicted Gram negative urine cultures with good sensitivity and high specificity. In conclusion, the UF-5000 represents a reliable tool for ruling-out urinary tract infections with high diagnostic accuracy and offers the possibility to detect Gram-negative bacteria in very high agreement with urine culture. Further investigations might reveal the potential for the Gram information for targeted antibiotic.
Rapid Screening of Urinary Tract Infection and Discrimination of Gram-Positive and Gram-Negative Bacteria by Automated Flow Cytometric Analysis Using Sysmex UF-5000.
Kim and colleagues evaluated the performance of the UF-5000 in context of UTI screening, aiming to reduce unnecessary urine culture and improve the determination of antibiotic treatments. The performance to discriminate Gram-negative bacteria was superior to that for Gram-positive bacteria with high sensitivity and specificity in ≥105 CFU/ml monobacterial samples. In conclusion, the UF-5000 demonstrated a potential utility for the rapid screening of negative bacterial cultures, depending on the respective patient population, requiring cut-off optimization.
Selection of Unnecessary Urine Culture Specimens Using Sysmex UF-5000 Urine Flow Cytometer.
This study investigated the potential of the UF-5000 to support the reduction of unnecessary urine cultures by ruling-out bacterial and fungal urinary tract infections. Applying urinalysis cut-off values of 50/µl and 100/l for bacteria and YLC, respectively, 84 out of 126 requested urine cultures were negative and could have been ruled-out by the UF-5000. In conclusion, the bacteria and yeast-like cell counts delivered by the UF-5000 could be used to predict negative cultures and reduce the load of urine cultures by around 10% without sacrificing positive cultures.
The importance of diagnosis gram-negative/gram positive bacteria in urine in the pre-culture screening of urine tract infections in the microbiology laboratory fluorescence flow cytometry on the UF-4000 urine analyser (Sysmex) for early initiation of targeted antibiotic therapy
This study investigated sensitivity and specificity of the UF-4000 for the discrimination between Gram-positive and Gram-negative bacteria in pre-culture screenings for urinary tract infections in a microbiology laboratory using fluorescence flow cytometry. Gram-positive and Gram-negative bacteria have been detected in urine, with sensitivities 78 % and 89 % and specificities of 96 % and 89 %, respectively. In conclusion, UF-4000 demonstrated a high potential in pre-culture screenings of urinary infections in a microbiology laboratory and is of benefit to the patient for its role in early initiation of antibiotic therapy, targeting Gram-positive or Gram-negative bacteria.
Evaluation of automated urine particle analyzer, UF-5000, as a screening tool to identify Gram stainability of urinal pathogens.
Kawamura and colleagues evaluated the performance of the UF-5000 with regards to the provision on information on the Gram status of bacterial cells via the BACT-info flag in comparison to conventional methods including Gram staining and quantitative bacterial culture. In summary, the UF-5000 presented in 83.2 % of UTI cases a Gram information, in line with classical Gram staining. The UF-5000 exhibited a high positive predictive value (93.3%) for both Gram negative staining and culture results. Thus, the UF-5000 using BACT-info shows great promise in screening for UTI pathogens and further improvements of judgement algorithms might make the Gram judgement even more reliable.
Cut-off values to rule out urinary tract infection should be gender-specific.
This study investigated the potential of urine flow cytometry of the UF-5000 to rule-out urinary tract infections and to reduce the load of urine culture samples. Applying cut-off value of >200 bacteria/μl, a sensitivity of 93.0%, a specificity of 63.5% and an NPV of 96.2% has been obtained. As a result, the culturing of 49% of all samples could be avoided. In addition, the data was retrospectively analyzed to determine if the introduction of gender-specific cut-off values could improve screening results. The obtained receiver operator curves are indeed significantly different when gender specific cut-offs were used. When an NPV of 95% is considered acceptable the unisex cut-off value of >200bacteria/μl can be used for women (NPV 94.9%), but the cut-off value for men could be raised to >400bacteria/μl without diminishing the NPV (NPV 95.0%).
Performance Evaluation / Comparison
Comparison of the diagnostic performance of two automated urine sediment analyzers with manual phase-contrast microscopy.
Enko and colleagues demonstrate that the analytical performance of the UF-5000 is in strong concordance with manual phase-contrast microscopy and clearly outperforming the Roche cobas® u 701 module. This study included a broad spectrum of urine sediment pathologies, thereby proving the UF-5000 to be a reliable tool for automated urine sediment analysis in daily clinical practice.
Performance of automated urine analyzers using flow cytometric and digital image-based technology in routine urinalysis.
This study evaluates the analytical performances of the UF-5000 and the Dirui FUS-200, to manual microscopy. Thereby, all available urinalysis aspects and sediment results were investigated within one hour after sample collection. Accurate results have been obtained from both analytical systems, the FUS-200 and the UF-5000, as good linearity without carry- over has been shown. Overall, the UF-5000 demonstrated better agreement in classification of WBCs, RBCs, ECs, positively affecting the morphologic recognition and enumeration of cells.
Comparison of five automated urine sediment analyzers with manual microscopy for accurate identification of urine sediment.
This study evaluated the analytical and diagnostic performance of the Sysmex UF-5000, the Roche cobas® u 701 module, the URiSCAN PlusScope and the Iris iQ200SPRINT and the SIEMENS UAS800 in comparison to manual microscopy. Each automated urine sediment analyzer has certain distinct features, in addition to the common advantages of reducing the burden of manual processing. Therefore, laboratory physicians are encouraged to understand these features, and to utilize each system in appropriate ways, considering clinical algorithms and laboratory workflow.
Evaluation of the analytical performances of Cobas 6500 and Sysmex UN-Series automated urinalysis systems with manual microscopic particle counting.
This study compared the diagnostic performance of the UF-5000 and the Roche cobas® u 701 module to manual microscopy. Comparing the quantification of WBCs and RBCs, the UF-5000 obtained the better sensitivities and specificities and showed high agreement with manual microscopy. In conclusion, the UF-5000 is a reliable tool for urine sediment analysis, but pathological samples should be confirmed by microscopy.
Performance evaluation of the new fully automated urine particle analyser UF-5000 compared to the reference method of the Fuchs-Rosenthal chamber.
Previtali and colleagues evaluated the analytical performance of the Sysmex UF-5000 for urine sediment samples compared manual particle counting using the Fuchs-Rosenthal chamber. The study demonstrated high linearity performances for RBCs, WBCs and epithelial cells, as well as high negative predictive values and good sensitivities and specificities for all parameters, especially those of clinical relevance. The authors conclude a high potential of the UF-5000 and its fluorescence flow cytometry technology to investigate urine sediment particles related to pathological conditions of the kidneys and the urinary tract.