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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 Please consider that conclusions of articles of this list may be based on low sample numbers or manuscripts that are not peer-reviewed yet (pre-prints).
COVID-19 and Haematology parameters
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
In this study the demographics, symptoms, comorbidities and lab results of 191 COVID-19 pneumonia patients were analysed from admission until either death or discharge from hospital differentiating survivors and non-survivors. Leucocytosis and lymphocytopenia were identified as risk factors associated with death in a univariant analysis, in terms of WBC differential parameters only the lymphocyte count is given in the data.
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China.
This article summarises demographics, symptoms, comorbidities and lab results of 138 COVID-19 patients with pneumonia from one hospital in Wuhan/China by differentiating ICU and non-ICU patients. Regarding haematology parameters the total WBC, neutrophil, lymphocyte, monocyte and platelet counts are given and data about the time course of total WBC count, neutrophils and lymphocytes in survivors and non-survivors.
Clinical and Biochemical Indexes From 2019-nCoV Infected Patients Linked to Viral Loads and Lung Injury.
The most common laboratory abnormalities were hypoalbuminaemia, lymphocytopenia, decreased LYMPH% and NEUT%, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8+ count. Age, viral load, lung injury score, albumin, CRP, LDH, LYMPH%, LYMPH#, and NEUT% may be predictors of disease severity.
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.
Based on 99 cases the 2019-nCoV infection is more likely to affect older males with comorbidities and can result in severe respiratory diseases. The lymphocyte count in most patients was reduced and this suggests that 2019-nCoV might mainly act on lymphocytes, especially T lymphocytes and this might be an important factor leading to exacerbations of patients.
Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis.
The authors summarise the behaviour of procalcitonin (PCT) in COVID-19 based on data of four articles. Although viral infections do not trigger PCT it shows an odds ratio of 4.76% in severe versus mild SARS-CoV-2 infections and Lippi et al. hypothesises that bacterial co-infections are the cause and thus suggests monitoring PCT over time to allow early detection of severe cases.
Hematologic parameters in patients with COVID-19 infection.
In conclusion, the study showed that on admission of SARS-CoV-2 positive patients, older age, lymphocytopenia and raised LDH were associated with ICU admissions. Patients who were transferred to the ICU showed over the course of time decreasing lymphocytes, monocytes and haemoglobin counts together with increasing neutrophil counts and strongly elevated LDH levels when compared to patients who did not require ICU stay.
Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage.
As of CBC parameters neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio (NLR) show significant differences between the groups of mild and severe course COVID-19 patients in this study. Based on age and NLR the authors propose a model for risk stratification and pneumonia patient management in hospital.
Laboratory abnormalities in patients with COVID-2019 infection.
This letter to the editor gives an overview on laboratory abnormalities in COVID-19 patients based on 11 Chinese studies. Detailed results of eight studies are given and as haematological abnormalities of unfavourable progression increased total WBC count, increased neutrophil count and decreased lymphocyte count are mentioned.
Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients.
The study identified potential immunological risk factors for COVID-19 pneumonia and provided clues for its clinical treatment. In contrast to most other studies the authors did not observe increased neutrophils or decreased lymphocytes.
Platelet-to-lymphocyte ratio is associated with prognosis in patients with Corona Virus Disease-19.
The authors suggest that the changes in the platelet-to-lymphocyte ratio (PLR) in peripheral blood during treatment could reflect the disease progression and prognosis of COVID-19 patients. In severe cases, the platelets significantly increased during treatment, which may be linked to the release of a large number of cytokines by the immune system.
Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity.
The presence of viral RNA in the blood is positively correlated with the severe disease stage. Early monitoring of virus RNA in blood on top of the respiratory tract might be beneficial for the prediction of disease stage progression.
Hypothesis for Potential Pathogenesis of SARS-CoV-2 Infection-A Review of Immune Changes in Patients With Viral Pneumonia.
In severe patients lymphocyte counts were significantly reduced. Non-survivors had higher levels of neutrophils, D-dimer, blood urea nitrogen and creatinine than the survivors.
Coronavirus infections and immune responses.
This review article summarises the mechanisms of innate and adaptive immune response in the context of past SARS, MERS and present SARS-CoV-2 infections and thus provides insights into the pathology of COVID-19.
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.
Eosinophil count in severe coronavirus disease 2019.
The systematic literature review of data on eosinophil count in patients with COVID-19 suggest that eosinopenia may not be associated with unfavourable progression of COVID-19.
Hematologic, Biochemical and Immune Biomarker Abnormalities Associated With Severe Illness and Mortality in Coronavirus Disease 2019 (COVID-19): A Meta-Analysis. Clin Chem Lab Med; 58(7): 1021
Based on 18 studies with reported laboratory data and comparison between COVID-19 patients with severe and non-severe disease the authors identified several biomarkers which may potentially aid in risk stratification for predicting severe COVID-19. The authors recommend clinicians to closely monitor WBC, LYMPH, PLT, IL-6 and serum ferritin as markers for potential progression to critical illness.
Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study.
The combination of eosinopenia and elevated hs-CRP can effectively identify suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms.
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.
Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular B cell activation.
Critically ill patients with COVID-19 robustly upregulate B cells producing high numbers of antibody-secreting cells. Specific B cell phenotype might serve as an immunological marker of severe COVID-19 infection at early stages.
Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.
In this time course study the authors confirmed lymphopenia in severe COVID-19 cases based on the decrease of CD8+ T cells but not a decrease in B cells or NK cells. The kinetics of most cytokines analysed show an inverse correlation with the T cell counts and the authors refer to a hypothesis about the function of T cells in regulating innate immune response in viral infection and thus reducing severe courses. Neutrophil-to-lymphocyte ratio (NLR) and Neutrophil-to-CD8+ T cell ratio (N8R) were identified as early indicators of severe course of COVID-19.
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.
COVID-19 and haemostasis parameters
ISTH interim guidance on recognition and management of coagulopathy in COVID‐19.
The ISTH interim guidance recommends measuring D-dimer, prothrombin time and platelet count in all patients suspected of having a COVID-19 infection, to decide whether patient admission and close monitoring is necessary or not. For a better and easy understanding, an algorithm to manage the COVID-19 coagulopathy based on simple laboratory markers is proposed in the appendix of the document. The authors also encourage measuring fibrinogen in COVID-19 positive patients, as recommended by the ISTH guidance on disseminated intravascular coagulation (DIC). Finally, the publication gives some advice on the use of LMWH treatment of COVID-19 positive patients.
Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.
This publication is investigating the contribution of heparin to surviving COVID-19 associated complications such as disseminated intravascular coagulopathy (DIC) or venous thromboembolism (VTE). 449 patients tested positive for COVID-19 were enrolled in this study in which 22% received heparin (mainly LMWH) treatment. The heparin treatment is associated with lower mortality in patients with a sepsis-induced coagulopathy (SIC) score ≥ 4, but not in those with a SIC score < 4. The mortality of patients with a D-dimer level > 3 μg/L was up to 20 % lower in heparin users than in non-users. Generally, increasing levels of D-dimer and PT (sec.) correlated with a higher 28-day mortality, while higher platelet counts correlated with a lower mortality.
Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A metaanalysis.
A low platelet count is associated with an increased risk of severe disease and mortality in patients with COVID-19.
Prominent changes in blood coagulation of patients with SARS-CoV-2 infection.
This paper presents the result of a comparison of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), antithrombin (AT), D-dimer and fibrin degradation products (FDP) in patients with SARS-CoV-2 (COVID-19) compared with a healthy population. Patients with COVID-19 were subdivided into three groups: mild, severe and critical. APTT and TT showed no significant differences between patients with COVID-19 and the control group. PT activity (%) and AT were lower in the COVID-19 group, with a descending tendency at an increasing level of the disease, but mostly remained within the reference ranges. FIB was elevated in COVID-19 patients at an equal level, regardless of the severity of the disease. D-dimer and FDP increased with the severity of the disease, with values generally appearing higher than in the control group.
Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China.
The publication reveals the results of a retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital. Elevated prothrombin time (PT) and D-dimer results were significantly associated with higher risks of developing Acute Respiratory Distress Syndrome (ARDS). Patients with ARDS who died later in the course of the disease presented significantly higher D-dimer levels than patients with ARDS who survived. In contrast to this, anomalies in PT were not associated with higher death rates in ARDS patients.
Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia.
Coagulation tests prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin activity (AT), fibrinogen (FIB), fibrin degradation product (FDP), and D-dimer were determined from 183 patients with confirmed novel coronavirus pneumonia (NCP, COVID-19) admitted to Tongji Hospital. Coagulation tests were performed in three-day intervals for 14 days in total. The non-survivors revealed significantly higher D-dimer and FDP levels, longer PT (sec.) and significantly lower AT levels compared with survivors on admission. A decrease in fibrinogen levels in non-survivors was found on days 10 and 14. DIC, mostly due to virus sepsis, appeared in most of the non-survivors.
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus – Infected Pneumonia in Wuhan, China.
This publication reveals the results of a retrospective, single-centre case study of 138 consecutively hospitalised patients with confirmed novel coronavirus pneumonia (NCP). The level of D-dimer is a promising prognostic marker for survival of the disease, with higher survival rates in patients with low D-dimer levels compared with those having high D-dimer levels.
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
This release presents the findings of 191 patients tested positive for COVID-19. The most frequently observed complication was sepsis. Most of the patients had an increased coagulation activity marked by elevated D-dimer concentrations. Found in most of the inpatients, this finding was associated with a higher mortality with increasing D-dimer levels at admission. Elevated prothrombin time (PT, sec.) results were not strongly associated with the disease or its outcome.
Clinical Features and Treatment of COVID-19 Patients in Northeast Chongqing
This publication describes the clinical and laboratory presentation of 135 patients tested positive for COVID-19. All patients had elevated D-dimer levels. Patients with a severe presentation of the disease had higher levels of D-dimer than patients with a mild form. Other haemostasis parameters were mostly within their normal ranges, but prothrombin time (PT, sec.) and activated partial thromboplastin time (APTT, sec.) were higher in patients with a severe form of the disease than in patients with a mild form.
Diagnostic Utility of Clinical Laboratory Data Determinations for Patients with the Severe COVID-19.
The study presents the results of investigations made on 43 adult patients tested positive for COVID-19 and which aimed at looking for a warning index for severe patient cases. Most patients presented with a mild form of the disease. Prothrombin time (PT) and activated partial thromboplastin time (APTT) levels were not significantly different between mild and severe cases. Thrombin time (TT), fibrinogen (FIB) and D-dimer levels were higher in patients with severe disease presentation than in those with mild cases. The study suggests interleukin-6 (IL-6) and D-dimer level determination having the highest specificity and sensitivity for an early prediction of severe clinical presentations of COVID-19.
Prelease from jth. Online version first published: 15 April 2020.
This letter to the editor refers to recently published findings in COVID-19-positive patients and gives new insights into the relation between COVID-19 and DIC based on autopsy results. A variable number of small fibrinous thrombi in small pulmonary arterioles in areas of both damaged and more preserved lung parenchyma have been found in eight out of the ten investigated fatal cases. Other indications of hypercoagulative processes found in these cases were endothelial tumefaction and a large number of pulmonary megakaryocytes in the pulmonary capillaries, as well as – in rare cases – small fibrinous thrombi in the glomeruli and superficial dermal vessels.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, blood coagulation, coagulopathy, autopsy.
Prelease from Thrombosis Research. Online version first published: 10 April 2020.
The publication presents the result of evaluating the incidence of the combined outcome of venous thromboembolism (VTE) and arterial thrombotic complications in all COVID-19 patients admitted to the intensive care unit of two Dutch university clinics and one Dutch teaching hospital. In total, 184 patients with proven COVID-19 pneumonia admitted to the ICU have been studied. The majority of patients were still on the ICU at the time the study ended, whereas 23 (13 %) died. All patients received at least standard doses of thromboprophylaxis. Most frequently found VTE was pulmonary embolism (PE). Prolongation of prothrombin time (PT, sec.) and activated partial thromboplastin time (APTT, sec.) are considered as independent predictors of thrombotic complications. Pharmacological thrombosis prophylaxis is recommended for all COVID-19 patients admitted to the intensive care unit, with an increase in doses from prophylactic to highly prophylactic ones.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, blood coagulation, coagulopathy, pulmonary embolism, deep vein thrombosis, stroke, thromboprophylaxis.
Published at Clinical Chemistry and Laboratory Medicine (CCLM), 20200369, eISSN 1437-4331, ISSN 1434-6621. First published online: 10 April 2020.
This publication analysed the findings of a total of 21 studies. Overall, the laboratory findings of 2,984 COVID-19 patients from 18 studies are compared between those with severe and with non-severe presentation of the disease. Additionally, the laboratory findings of three studies with 393 patients are compared between patients who survived and those who did not. Prothrombin time (PT) and D-dimer are elevated in patients with severe or fatal COVID-19. Non-survivors had more significant decreases in lymphocyte and platelet counts compared with survivors.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, blood coagulation, clinical chemistry.
Online version first published: 10 April 2020.
This publication suspects that micro thromboses manifested in organs and as disseminated intravascular coagulation (DIC) in critically ill COVID-19 patients causes livedo reticularis (LR). Two cases of transient LR, from which the patients recovered fully, are reported. This finding of LR seems to be different to SARS-CoV and MERS-CoV. Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, livedo reticularis, disseminated intravascular coagulation.
Online version first published: 13 April 2020.
This review article highlights clinical and laboratory presentation of COVID-19 patients to give guidance for early prevention and management of the disease. Signs of major blood hypercoagulability, namely elevated levels of D-dimer, FDP, activated partial thromboplastin time (APTT) and prothrombin time (PT), as well as a reduced activity of antithrombin were commonly found in patients with COVID-19. The levels of D-dimer and FDP are significantly higher in non-survivors than in survivors. Careful evaluation of laboratory indices at baseline and throughout the course of the disease is advised for a tailored, efficient treatment and thromboprophylaxis, contributing to the survival rate of the affected patients.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, coagulation.
First published online: 9 April 2020.
This review article summarises the findings of publications about COVID-19 and diabetes. Some studies did not find a clear association between diabetes and severity of the disease while others indicated that older patients with chronic diseases including diabetes were at higher risk of severe COVID-19 courses and mortality. SARS-CoV-2 possibly triggers higher stress conditions in patients with diabetes, with a greater release of hyperglycaemic hormones leading to increased blood glucose levels and abnormal glucose variability. Around 10% of the patients with type-2 diabetes mellitus and COVID-19 suffered at least one episode of hypoglycaemia (< 3.9 mmol/L), causing the mobilisation of pro-inflammatory monocytes and an increase of platelet reactivity. These conditions contribute to a higher cardiovascular mortality in patients with diabetes. Besides the inflammatory processes, an imbalance between coagulation and fibrinolysis occurs, with increased levels of clotting factors and relative inhibition of the fibrinolytic system. Both insulin resistance and type-2 diabetes mellitus are associated with endothelial dysfunction, and enhanced platelet aggregation and activation. In addition to atherosclerosis, vascular inflammation and endothelial dysfunction, these abnormalities contribute to the development of a hypercoagulable pro-thrombotic state.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, diabetes, coagulopathy, coagulation.
First published: 9 April 2020.
This publication reveals the incidence of VTE in a retrospective study of 81 patients tested positive for COVID-19 at Union Hospital, Wuhan over a period of nearly two months. 25 % of patients with a severe presentation of COVID-19 developed a deep venous thrombosis in their lower limbs. Higher age, lower lymphocyte counts, prolonged activated partial thromboplastin time (APTT) and elevated D-dimer levels have been reported in these patients frequently. Even though D-dimer levels were above the normal range in both VTE and non-VTE patients, D-dimer was elevated to a remarkably higher extent in VTE patients. The incidence of DIC in non-survivors was 71.4 %, suggesting that abnormal blood coagulation and thrombosis are associated with poor prognosis in patients with COVID-19. Furthermore, the paper implies to increase the D-dimer cut-off level to predict VTE in COVID-19-positive patients.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, D-dimer, coagulopathy, coagulation, venous thromboembolism.
First published: 8 April 2020.
This publication reports utility of tissue plasminogen activator (t-PA, Alteplase) in three cases of critically ill, mechanically ventilated COVID-19-positive patients with ARDS and respiratory failure. All three cases showed initial improvement of the respiratory conditions. However, the improvements were transient only, and the respiratory conditions of all patients deteriorated after terminating the tPA therapy. The paper concludes that the utility of larger bolus tPA (with or without anticoagulation) to prevent the recurrence of suspected pulmonary microvascular thrombosis in COVID-19 ARDS should be investigated in further studies.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, Tissue Plasminogen Activator (tPA), fibrinolysis, coagulation, Acute Respiratory Distress Syndrome (ARDS).
First published: 3 April 2020.
This publication investigates the differences of coagulation features between severe pneumonia induced by SARS-CoV-2 and non-SARS-CoV-2. Four hundred and forty-nine patients classified as a COVID group, and 104 patients classified as a non-COVID group were enrolled in this study. Compared with the non-COVID group, patients of the COVID group were older, had higher platelet counts, and their mortality was almost twice as high. In patients with D-dimer levels exceeding the upper normal limit sixfold, a significantly lower mortality among heparin (mainly LMWH) users than among non-users was found in the COVID group, while no difference in the mortality between heparin users and non-users could be found in the non-COVID group when being stratified by D-dimer. However, anticoagulant therapy may not benefit unselected patients, whether in the COVID or non-COVID group.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, D-dimer, coagulopathy.
First published: 22 March 2020.
The clinical presentation of 17 patients tested positive for COVID-19 has been reported in this publication. While fever and cough were reported most frequently, dyspnoea and fatigue were rarer, and none of the patients had diarrhoea. The publication could not reveal any difference in D-dimer levels between patients with a worsening condition and stable patients. In contrast to this, significantly decreased total lymphocyte counts were found in patients with a worsening condition.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, D-dimer, coagulopathy.
First published: 31 March 2020.
This publication is a retrospective study of 174 patients with SARS-Cov-2 infection who were admitted to Wuhan Union hospital from 10 February 2020 to 29 February 2020. Patients with diabetes were at higher risk of severe pneumonia, the release of tissue injury-related enzymes, excessive inflammation response, and hypercoagulable state associated with dysregulation of glucose metabolism. D-dimer levels were significantly higher in patients with type 2 diabetes mellitus than in those without.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, D-dimer, diabetes.
First published online: 25 March 2020.
In this publication, three leading infectious disease experts in China share their observations in the management of COVID-19 patients. In the clinical course of the disease and with a worsening of the symptoms, D-dimer values increased from mildly to significantly elevated, along with prolonged prothrombin time (PT), and a gradual decrease of fibrinogen (FBG) and platelets. The clinical and laboratory manifestations are consistent with the diagnosis of the hypercoagulable phase of DIC. It is assumed that COVID-19 can activate the coagulation cascade through various mechanisms, leading to severe hypercoagulability. Low molecular weight heparin (LMWH) treatment may prevent further clot formation and reduce microthrombi. Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, coagulopathy, low molecular weight heparin, clinical management, antiviral drugs.
First published: 19 April 2020.
Based on the outcome of 343 patients tested positive for COVID-19 and their survival rate, this publication recommends using a higher cut-off value for D-dimer to predict the mortality of patients on hospital admission. The authors state to use a cut-off four times higher than the cut-off recommended by the reagent manufacturer for the exclusion of VTE in patients. Patients with a D-dimer result above this COVID-19 D-dimer cut-off have a higher mortality than patients with a D-dimer level below it.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, D-dimer, mortality, prognosis, CS-5100.
First published: 08 April 2020.
The letter to the editor shares the outcome of the clot waveform analysis (CWA) evaluation of the APTT results from three patients tested positive for COVID-19 and admitted to the ICU. None of the patients had an underlying malignancy, bleeding or thrombotic disorder, nor were they under antithrombotic therapy on admission. The APTT values were moderately prolonged. The author indicates that there is a relation between the increase of the CWA parameter and a worsening of the severity of the COVID-19 infection. Furthermore, differences in the CWA parameter between COVID-19 and other viral or bacterial infections are reported.
Keywords: Corona Virus Disease 2019, SARS-CoV-2, COVID-19, clot waveform analysis (CWA), CS-2100, CS-2500.
Focus on the crosstalk between COVID-19 and the urogenital systems.
This short editorial comment reflects the potential effects of the SARS-CoV-2 infection on urogenital systems. SARS-CoV-2 utilises the ACE2-receptor (ACE2 = angiotensin-converting enzyme II) for entering target cells. The ACE2-receptor is also expressed on cells of the proximal renal tubule, the bladder urothelial and cells of the male reproductive system.
In summary, more attention should be paid on COVID-19 patients with chronic urological histories, as comorbid conditions, such as chronic kidney disease and urological malignancies contribute to a weaker immune system, increasing the risk to be infected by SARS-CoV-2.
The value of urine biochemical parameters in the prediction of the severity of the corona virus disease 2019.
The authors of this study aimed to evaluate the potential urine biochemistry parameters in predicting disease severity in addition to diagnosis by viral nucleic acid test and auxiliary haematology diagnostic parameters. The relationship between urinalysis parameters and COVID-19 disease severity were investigate on 119 patients at Wuhan University Hospital grouping patients according to disease severity into healthy, moderate, severe and critical.
In general, COVID-19 patients showed haematuria and proteinuria, increased pH values and decrease specific gravity, if compared to healthy individuals. Within the population of COVID-19 patients, urinary glucose and protein levels were significantly higher within the severe and critical cohorts. Other urine biochemistry parameters seemed not to be related to the severity of COVID-19.
In conclusion, some urinary are parameters might complement the differentiation between healthy and COVID-19-positive individuals and urinary glucose and protein levels might be suitable parameters to distinguish between different stages of disease severity.
Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19).
Inspired by Liu et al. and the potential use of urinalysis parameters in discrimination of the COVID-19 disease severity, the authors of this study provide a deeper insight into urinalysis parameters and their potential for accurate risk stratification of progressing toward severe or critical disease, especially as the urinary tract is commonly involved in COVID-19 infections.
From 226 patients admitted to the emergency department for COVID-19, 45 patients showed a more severe condition from CT imaging and were in the emergency department and included in this study. Urinalysis was carried out using Aution Max AX-4030 and SediMax systems. Patients with a history of diabetes or kidney disease were excluded.
All 226 COVID-19-positive patients showed proteinuria and haematuria at point of admission. In addition, urine sediment analysis revealed the presence of erythrocytes and casts in nearly half of all patients. Comparing the two study cohorts ‘In-hospital deaths’ and ‘Discharged’
Showed a more frequent presence of granular cylinders and tubular cells in the urine of patients who died. Higher abnormal rates of urea and creatinine values reflected renal impairment, which might be a significant predictor of an unfavourable disease progression.
In conclusion, urinalysis should be regularly performed in all COVID-19 patients to obtain additional information for optimisation of patient management and risk prediction.
COVID-19-associated nephritis: early warning for disease severity and complications?
Since SARS-CoV-2 uses the ACE2 receptor to enter its target cells, also renal podocytes are a potential target of this corona virus. In concordance with post-mortem analysed histopathology samples that showed glomerular injury and nephritis-like histology, SARS-CoV-2 infections can induce nephritis.
Nephritis can cause a severe course of infection by inducing a capillary leak syndrome, a systemic condition in which plasma fluid and proteins leak from capillary vessels into the surrounding tissue. This results in hypotension, hypoalbuminemia and a reduced haemoconcentration, finally leading to respiratory decompensation that requires ICU admission and ventilation.
In this correspondence, the authors conclude that analysis of urine specimens at the point of hospital admission for COVID-19 patients could help to identify patients with a COVID-19-associated nephritis and the risk for respiratory decompensation. The risk for these patients is elevated, if two or three conditions of leucocyturia, albuminuria or haematuria are fulfilled.
Chronic kidney disease is associated with a severe coronavirus disease 2019 (COVID-19) infection.
Since chronic Kidney disease (CKD) is associated with an increased risk of both inpatient and outpatient pneumonia, causing an 14 to 16-fold increase in the mortality rate in CKD patients seems to be 14–16, the authors conducted a meta-analysis to explore the potential association between CKD and severity of the COVID-19 infection.
A meta-analysis was performed on retrievable data, including the estimation of the odds ratio (OR) and its 95% confidence interval (95% CI) in patients with or without severe forms of COVID-19.
Finally, four studies were included, including 1389 COVID-19 patients, among which 273 (19.7%) were classified as having severe disease. Although no study individually found CKD as significant clinical predictor, the meta-analysis revealed a significant association of CKD with a severe course of COVID-19 infection.
In conclusion, CKD seems to be associated with enhanced risk of severe COVID-19 infection.
Chronic kidney disease is Kidney disease is associated with in-hospital death of patients with COVID-19.
This study prospectively investigated the link between renal involvement and observed mortality rate. Out of 701 patients, hospitalised for COVID-19, 43.9 % showed proteinuria and 26.7 % showed haematuria. Furthermore, increased prevalence for increased creatinine and urea levels and reduced glomerular filtration rates were observed.
The authors conclude that these parameters are independent risk factors for morbidity and that renal damage is a major complication in COVID-19.
COVID-19 and acute kidney injury in hospital: summary of NICE guidelines.
Acute kidney injury (AKI) is observed in a subset of COVID-19 patients, significantly increasing the risk of mortality. AKI can occur at all stages of COVID-19 infection, demanding clinical vigilance and consideration of risk factors for AKI alongside early detection and diagnosis are essential components of general supportive care.
This article summarises key points from the National Institute for Health and Care Excellence (NICE) COVID-19 rapid guideline on AKI in hospital.
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
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 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
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 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.
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.
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.