Parameters of the complete blood count predict in hospital mortality.

INTRODUCTION: Mortality rates are used to evaluate the quality of hospital care after adjusting for disease severity and, commonly also, for age, comorbidity, and laboratory data with only few parameters of the complete blood count (CBC). OBJECTIVE: To identify the parameters of the CBC that predict independently in-hospital mortality of acutely admitted patients. POPULATION: All patients were admitted to internal medicine, cardiology, and intensive care departments at the Laniado Hospital in Israel in 2018 and 2019. VARIABLES: Independent variables were patients' age, sex, and parameters of the CBC. The outcome variable was in-hospital mortality. ANALYSIS: Logistic regression. In 2018, we identified the variables that were associated with in-hospital mortality and validated this association in the 2019 cohort. RESULTS: In the validation cohort, a model consisting of nine parameters that are commonly available in modern analyzers had a c-statistics (area under the receiver operator curve) of 0.86 and a 10%-90% risk gradient of 0%-21.4%. After including the proportions of large unstained cells, hypochromic, and macrocytic red cells, the c-statistic increased to 0.89, and the risk gradient to 0.1%-29.5%. CONCLUSION: The commonly available parameters of the CBC predict in-hospital mortality. Addition of the proportions of hypochromic red cells, macrocytic red cells, and large unstained cells may improve the predictive value of the CBC.

Necessity of flow cytometry assessment of circulating plasma cells and its connection with clinical characteristics of primary and secondary plasma cell leukaemia.

Plasma cell leukaemia (PCL) is a rare and very aggressive plasma cell disorder. Preventing a dismal outcome of PCL requires early diagnosis with appropriate analytical tools. Therefore, the investigation of 33 patients with primary and secondary PCL was done when the quantity of circulating plasma cells (PCs) using flow cytometry (FC) and morphology assessment was evaluated. The phenotypic profile of the PCs was also analysed to determine if there is an association with clinical outcomes and to evaluate the prognostic value of analysed markers. Our results revealed that FC is an excellent method for identifying circulating PCs as a significantly higher number was identified by FC than by morphology (26·7% vs. 13·5%, P = 0·02). None of secondary PCL cases expressed CD19 or CD20. A low level of expression with similar positivity of CD27, CD28, CD81 and CD117 was found in both PCL groups. A decrease of CD44 expression was detected only in secondary PCL. Expression of CD56 was present in more than half of PCL cases as well as cytoplasmic nestin. A decreased level of platelets, Eastern Cooperative Oncology Group score of 2-3 and lack of CD20+ PC were associated with a higher risk of death. FC could be incorporated in PCL diagnostics not only to determine the number of circulating PCs, but also to assess their phenotype profile and this information should be useful in patients' diagnosis and possible prognosis.

Assessing abdominal pain in adults: a rational, cost-effective, and evidence-based strategy.

The management of abdominal pain has changed significantly in the past 20 years, with increasing emphasis on identifying patients who are at high risk for occult pathology and worse outcomes. Emphasizing safe disposition over diagnosis, this issue identifies the important aspects of the history and physical examination, explores strengths and weaknesses of laboratory evaluations, and summarizes the pros and cons of the many types of imaging now available. With abdominal pain still the most common chief complaint seen in the emergency department, a new look at the evolution of assessment strategies is in order, such as new recommendations on the use of oral contrast, managing HIV patients on highly active antiretroviral therapy, maximizing use of bedside ultrasound, when and how to offer pain relief, and the value of serial examinations and observation to reduce costs and improve care.

Prognostic value of the systematic immune-inflammation index among patients with operable colon cancer: A retrospective study.

The systematic immune-inflammation index (SII) has been used to predict the prognosis of patients with various cancers. This study aimed to determine whether the preoperative SII was associated with postoperative survival among patients with operable colon cancer.This retrospective study included 118 age- and sex-matched healthy subjects and 118 patients who underwent radical surgery for colon cancer between January 2011 and December 2013. The preoperative SII was calculated based on counts of neutrophils, lymphocytes, and platelets in the peripheral blood. Pearson correlation analysis was used to analyze the relationships between the SII and carcinoembryonic antigen (CEA) concentration, average length of stay (ALOS), and medical costs during hospitalization. The χ test or Fisher exact test was used to analyze the relationship between the preoperative SII and the postoperative survival rate.The median SII value was 667.75 among patients with colon cancer, which was higher than the value among healthy subjects. A high SII (>667.75) was associated with a large tumor size and advanced TNM stage, although it was not associated with age, sex, tumor location, or pathological grade. Pearson correlation analysis revealed that the SII was positively correlated with serum CEA concentration, ALOS, and medical costs. Relative to a low SII, a high SII was significantly associated with a lower overall survival rate at 3 years and 5 years after surgery.The present study's findings suggest that the preoperative SII is a useful prognostic index for patients with operative colon cancer.

A standardized flow cytometry network study for the assessment of circulating endothelial cell physiological ranges.

Circulating endothelial cells (CEC) represent a restricted peripheral blood (PB) cell subpopulation with high potential diagnostic value in many endothelium-involving diseases. However, whereas the interest in CEC studies has grown, the standardization level of their detection has not. Here, we undertook the task to align CEC phenotypes and counts, by standardizing a novel flow cytometry approach, within a network of six laboratories. CEC were identified as alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in 269 healthy PB samples. Standardization was demonstrated by the achievement of low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of Median Fluorescence Intensity values of the most stable antigens that allowed CEC identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale = 11.55 CEC/mL). CEC count biological variability and method specificity were finally assessed. Results, obtained on a large population of donors, demonstrate that the established procedure might be adopted as standardized method for CEC analysis in clinical and in research settings, providing a CEC physiological baseline range, useful as starting point for their clinical monitoring in endothelial dysfunctions.

Marrow Hypocellularity, But Not Residual Blast Count or Receipt of Reinduction Chemotherapy, Is Prognostic on Day-14 Assessment in Acute Myeloid Leukemia Patients With Morphologic Residual Disease.

BACKGROUND: Induction chemotherapy for acute myeloid leukemia (AML) is based on the "7+3" cytarabine/anthracycline regimen. A nonhypocellular day 14 (D14) bone marrow sample with a blast count > 5% to 10% is suggestive of residual leukemia, for which a second course of induction chemotherapy has been recommended. Although the prognostic value of D14 bone marrow findings has been established, its use as a decision point is controversial because the benefit of repeat induction has been questioned. PATIENTS AND METHODS: In the present single-center retrospective study of 113 patients with newly diagnosed AML, we evaluated the role of cellularity on the clinical outcomes of patients with residual morphologic leukemia (blasts ≥ 5%). Among 64 patients with D14 bone marrow samples, 31 had residual morphologic leukemia. RESULTS: The complete remission (CR) rates were greater for the hypocellular (11 of 16) than for the nonhypocellular (4 of 15) patients (P = .03). The median overall survival (OS) for the hypocellular D14 patients was longer than that for the nonhypocellular patients (17 vs. 8 months; P = .02). No significant difference between the receipt of reinduction therapy and CR or OS was found on logistic or survival model analysis. The specificity for residual leukemia on D14 bone marrow samples was better for cellularity ≥ 20% and blasts ≥ 20% than for blasts ≥ 5%. CONCLUSION: The results of our study have shown that patients with < 20% cellularity and < 20% blasts on the D14 bone marrow assessment should continue observation until recovery rather than receive additional immediate therapy.

Performance of a cost-effective and automated blood counting system for resource-limited settings operated by trained and untrained users.

Current flow-based blood counting devices require expensive and centralized medical infrastructure and are not appropriate for field use. In this article we report a streamlined, easy-to-use method to count red blood cells (RBC), white blood cells (WBC), platelets (PLT) and 3-part WBC differential through a cost-effective and automated image-based blood counting system. The approach consists of using a compact, custom-built microscope with large field-of-view to record bright-field and fluorescence images of samples that are diluted with a single, stable reagent mixture and counted using automatic algorithms. Sample collection utilizes volume-controlled capillary tubes, which are then dropped into a premixed, shelf-stable solution to stain and dilute in a single step. Sample measurement and analysis are fully automated, requiring no input from the user. Cost of the system is minimized through the use of custom-designed motorized components. We compare the performance of our system, as operated by trained and untrained users, to the clinical gold standard on 120 adult blood samples, demonstrating agreement within Clinical Laboratory Improvement Amendments guidelines, with no statistical difference in performance among different operator groups. The system's cost-effectiveness, automation and performance indicate that it can be successfully translated for use in low-resource settings where central hematology laboratories are not accessible.

Invasive and non-invasive assessment of portal hypertension.

Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.

Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy.

OBJECTIVE: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). METHODS: The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. RESULTS: Three inflammation markers (ratios of blood cell counts) were positively correlated (p < 0.0001). The PNI and the BMI were positively correlated (p = 0.04), although they were inversely correlated with the three inflammation markers (p < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. CONCLUSIONS: The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC.

Multicenter study to evaluate a new enumeration method for hematopoietic stem cell collection management.

BACKGROUND: CD34 flow cytometry is the gold standard for stem cell enumeration in peripheral blood at the mobilization stage and in the final apheresis product. The new stem cell mode of the Sysmex XN Series analyzer enumerates an immature cell population in the white progenitor and pathological cell (WPC) channel, based on the cell size, internal cellular complexity, and fluorescence intensity. STUDY DESIGN AND METHODS: In this multicenter study we analyzed 147 peripheral blood samples, 22 samples during collection of stem cells, and 45 samples from the apheresis product of 18 healthy allogeneic donors and 84 autologous patients. RESULTS: In this multicenter study we demonstrate that the XN stem cell enumeration method correlates well with viable CD34+ cells determined by flow cytometry during the stem cell mobilization phase to determine apheresis start time, during apheresis for real-time monitoring and adjustment, and for quality control of the final stem cell harvest. CONCLUSION: Our data show that there is an improvement in the correlation of XN stem cells and CD34+ cells in the peripheral blood during stem cell mobilization as well as in stem cell harvests compared to SE or XE Series analyzers. The XN stem cell enumeration method has a number of advantages compared to CD34 flow cytometry: it is fast, simple, reproducible, and less expensive. CE marking for the European market has been obtained, making the stem cell count on the XN analyzer a reportable clinical variable.

Evaluation of derived Coulter red blood cell parameters for the assessment of iron deficiency in adults with congenital heart disease.

INTRODUCTION: The aim of our study was to evaluate derived red blood cell parameters in determining the presence of iron depletion and iron-deficient erythropoiesis, as states that precede iron deficiency anemia, in adults with congenital heart disease. METHODS: Eighty-eight adults who were diagnosed with congenital heart disease were divided into two groups (cyanotic and acyanotic). In both groups, congenital heart disease patients were then divided into three subgroups: with iron depletion, with iron-deficient erythropoiesis, and a control group. The following parameters were measured: complete blood count, reticulocytes, ferritin, soluble transferrin receptor, haptoglobin, lactate dehydrogenase, and calculated parameters: low hemoglobin density (LHD), red cell size factor (RSF), and microcytic anemia factor (MAF). RESULTS: Discriminant analysis indicated statistically significant differences in the first discriminant function: Function 1 - body iron, LHD, MAF, sTfR, and RSF (P < 0.001) in patients with acyanotic congenital heart disease and significant differences in both discriminant functions in patients with cyanotic congenital heart disease: Function 1 - body iron, soluble transferrin receptor, LHD, RSF, MAF, lactate dehydrogenase, and haptoglobin (P = 0.008) and Function 2 - reticulocytes (#), immature reticulocyte fraction and reticulocytes (%) (P = 0.049). CONCLUSIONS: Beside parameters that describe iron metabolism dynamics (body iron and soluble transferrin receptor), LHD, indicator of hypochromia, have the highest potential to differentiate and classify iron deficiency in patients with congenital heart disease.

Approach to peripheral blood film assessment for pathologists.

In today's age of advanced technology used in the diagnosis of many medical problems, the blood film stands out as an inexpensive and quick diagnostic tool that can generally be performed in most laboratories. Understanding when to perform a blood film and how it is made and having an organized sequential approach to reviewing the blood film are critical in the efficient use of this ubiquitous laboratory investigation. This article will review these issues, as well as common morphologic abnormalities found on blood films, and will discuss related clinical diagnoses that they represent. The final step of communicating the blood film findings in a clear and concise method to relay clinical suspicions to the end user will be discussed.

Health utilities associated with hemoglobin levels and blood loss in postmenopausal women: the Women's Health Initiative.

OBJECTIVES: The purpose of our study was to use health-related quality of life data from the Women's Health Initiative to calculate health-related utility weights and examine differences in these health utility weights across different hemoglobin (Hgb) levels. These utility weights could then be used in future cost-effectiveness studies. METHODS: Health utility weights were measured by the Short Form-6D (SF-6D), a health utility index derived from the Short Form Medical Outcomes questionnaire. Adjusted least square means were calculated for each level of Hgb at baseline and in longitudinal regression analysis the relationship between change in Hgb and change in the SF-6D was examined. Both baseline and longitudinal analyses were performed for all postmenopausal women and separately for those with self-reported heart failure, cancer, and osteoarthritis. RESULTS: Women with Hgb in the anemic range had lower health utility weights than those with higher Hgb levels. Longitudinally, a loss of of 2 g/dl Hgb or more was associated with a statistically significant and clinically meaningfully decline in SF-6D in all participants and also in the group of participants with cancer and osteoarthritis, but not in those with heart failure. CONCLUSIONS: Lower levels of Hgb and a loss of Hgb are associated with a statistically significant and clinically meaningful decrement in health utility in all postmenopausal women we studied and also in those with chronic conditions.

Flow cytometric CD34+ stem cell enumeration: lessons from nine years' external quality assessment within the Benelux countries.

BACKGROUND: A biannual external quality assurance (EQA) scheme for flow cytometric CD34+ haematopoietic stem cell enumeration has been operational in the Benelux countries since 1996. In an evaluation of the results of 16 send-outs, we studied the effects of the methods used on assay outcome and whether or not this exercise was effective in reducing between-laboratory variation. METHODS: Data were analyzed using robust multivariate regression. This approach is relatively insensitive to outliers and is used to assess the effect of methodological aspects of CD34+ cell counting on the bias and variability. RESULTS: Five variables were associated with significant bias of absolute CD34+ cell counts: (i) unique laboratory number (ULN), (ii) gating strategy; (iii) CD34 mAb fluorochrome; (iv) type of flow cytometer, and (v) method of sample preparation. In addition, ULN and platform methodology (i.e., single vs. dual) contributed significantly to the variability of this assay. Overall, the variability in results of CD34+ cell enumeration has declined with time; in particular, after a practical workshop in which participants were trained to use the "single platform ISHAGE protocol." CONCLUSIONS: Between-laboratory variation in CD34+ cell enumeration can be reduced by standardization of methodologies between centres. Our approach, i.e., EQA with targeted training and feedback in response to reported results, has been successful in reducing the variability of CD34+ cell enumeration between participants.

Deceptive multilineage reconstitution analysis of mice transplanted with hemopoietic stem cells, and implications for assessment of stem cell numbers and lineage potentials.

Hemopoietic stem cells (HSC) are identified through their unique ability, at the single cell level, to long-term reconstitute all blood cell lineages. Sustained myeloid reconstitution is considered the hallmark of HSC, because myeloid progenitors and their progeny have very short half-lives. Here we demonstrate that the established practice of relying on RB6-8C5 as a myeloid specific Ab can result in overestimation of HSC frequencies because the RB6-8C5 Ab also detects Ags expressed on a sizeable population of CD3(+)CD8(+) T cells, constitutively as well as following transplantation. Likewise, a high fraction of mice transplanted with limiting numbers of ex vivo expanded Lin(-)Sca(+)kit(+)CD34(-) HSC show long-term RB6-8C5(+)CD3(+) (lymphoid) but no RB6-8C5(+)CD3(-) (myeloid) reconstitution. Most noteworthy, the use of RB6-8C5 as a myeloid specific Ab can be deceptive by implicating the existence of lineage-restricted HSC capable of long-term reconstituting the myeloid and T, but not B, cell lineage. Because cross-lineage expression of "lineage-specific" markers is unlikely to be unique to the blood system, claims of unexpected cell fates should be substantiated not only by acquisition of lineage-specific markers, but also absence of markers of other lineages normally derived from the investigated stem cells.

Evaluación del desempeño de contadores hematológicos / Performance assessment of blood cells analyzers

El objetivo de esta presentación es brindar, en forma didáctica y actualizada, una orientación para la evaluación de contadores hematológicos. Primeramente se hace referencia a los niveles de evaluación, la información preliminar referida al instrumento sobre requerimientos de espacio y servicios y al manual de instrucción. En cuanto a las etapas de evaluación se tratan: a) la planificación técnica que incluye acuerdos previos con el fabricante y la planificación de recursos internos; b) calibración, calibradores y materiales de control; c) reactivos; d) muestras: su manipulación y registros de datos; e) ensayo preliminar: normas de seguridad (mecánicas, eléctricas, microbiológicas, químicas, ambientales) e instalación y mantenimiento; f) evaluación del desempeño: efecto de la dilución, coincidencia, precisión intra e interensayo, deriva, evaluación del arrastre, comparabilidad con datos obtenidos por procedimientos de rutina, exactitud, efecto del envejecimiento de la muestra, sensibilidad para muestras anormales, interferencias, análisis de datos y utilidad clínica; g) evaluación de la eficiencia. Finalmente, se sacan conclusiones sobre la base de un ejemplo de evaluación de un equipo de apertura-impedancia