Assessing Accuracy and Precision of Hemoglobin Determination in Venous, Capillary Pool, and Single-Drop Capillary Blood Specimens Using three Different HemoCue® Hb Models: The Multicountry Hemoglobin Measurement (HEME) Study.

BACKGROUND: Anemia prevalence estimates reported in population surveys can vary based on the blood specimen source (capillary or venous) and analytic device (hematology autoanalyzers or portable hemoglobinometers) used for hemoglobin (Hb) determination. OBJECTIVES: This study aimed to compare accuracy and precision of Hb measurement in three blood specimen types on three models of hemoglobinometers against the results from venous blood from the same individuals measured on automated analyzers (AAs). METHODS: This multisite (Cambodia, Ethiopia, Guatemala, Lebanon, Nigeria, and Tanzania) study assessed Hb measurements in paired venous and capillary blood specimens from apparently healthy women (aged 15-49 y) and children (aged 12-59 mo) using three HemoCue® Hb models (201+, 301, and 801). Measurements were compared against reference values: venous blood in hematology AA and adjusted via regression calibration or mean difference in HemoCue® Hb. Venous, capillary pool, and single-drop capillary blood specimens were assessed for accuracy and precision. RESULTS: Venous blood measured using HemoCue® Hb 301 exhibited a positive mean error, whereas responses in HemoCue® Hb 201+ and 801 were nondirectional compared with the reference. Adjustment with the reference harmonized mean errors for all devices across study sites to <1.0 g/L using venous blood. Precision was highest for venous blood (±5-16 g/L) in all sites, lowest for single-drop capillary (±9-37 g/L), and intermediate (±9-28 g/L) for capillary pool blood specimen. Imprecision differed across sites, especially with both capillary blood specimens, suggesting different levels of personnel skills. CONCLUSIONS: Findings suggest that venous blood is needed for accurate and precise Hb determination. Single-drop capillary blood use should be discouraged owing to high measurement variability. Further research should evaluate the viability and reliability of capillary pool blood for this purpose. Accuracy of HemoCue® Hb devices can be improved via standardization against results from venous blood assessed using AA.

Clinical utility of point-of-care glucose testing in the assessment of gestational diabetes: Prospective cohort study.

OBJECTIVE: To assess the clinical utility of point-of-care (POC) capillary blood glucose (CBG) testing in the assessment of gestational diabetes mellitus (GDM) during oral glucose tolerance test (OGTT). DESIGN: Prospective cohort study. SETTING: Antenatal clinics at King's College Hospital. POPULATION: Women screened for GDM between March and June 2020. METHODS: The CBG was measured using the POC StatStrip® test and the venous plasma glucose (VPG) was measured by Roche analyser (Cobas 8000 c702). GDM was diagnosed based on the 2015 National Institute for Health and Clinical Excellence (NICE) Clinical Guideline criteria. The two methods were compared statistically using Analyse-It 5.40.2. MAIN OUTCOME MEASURES: Diagnostic sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the POC StatStrip® test, compared with VPG measured by reference laboratory method. RESULTS: A total of 230 women were included. The number and percentage of women with glucose concentrations above the GDM threshold using the POC StatStrip® test versus laboratory VPG measurement was 15 (6.5%) versus eight (3.4%) at fasting and 105 (45.6%) versus 72 (31.1%) at 2 h, respectively. The sensitivity and specificity values (and 95% CIs) for the POC StatStrip® test were 88% (52%-99%) and 97% (93%-98%) at fasting and 97% (91%-99%) and 79% (71%-84%) at 2 h, respectively. However, the specificity and the NPV for the POC StatStrip® test for concentrations of ≤5.0 mmol/L at fasting or <7.5 mmol/L at 2 h were 100%, and the sensitivity and the PPV for concentrations of >9.5 mmol/L at 2 h were 100%. CONCLUSIONS: In our cohort the POC measurement of CBG cannot entirely replace the laboratory method for the OGTT; however, it can be used to rule out/rule in GDM for glucose concentrations of ≤5.0 mmol/L at fasting or <7.5/>9.5 mmol/L at 2 h.

Feasibility, reliability and satisfaction of (automated) capillary carcinoembryonic antigen measurements for future home-based blood sampling: the prospective CASA-I study.

AIM: Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection. METHODS: Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference. RESULTS: The Pearson's correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use. CONCLUSION: This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling.

Retinal perfusion is linked to cognition and brain MRI biomarkers in Black Americans.

INTRODUCTION: We investigated whether retinal capillary perfusion is a biomarker of cerebral small vessel disease and impaired cognition among Black Americans, an understudied group at higher risk for dementia. METHODS: We enrolled 96 Black Americans without known cognitive impairment. Four retinal perfusion measures were derived using optical coherence tomography angiography. Neurocognitive assessment and brain magnetic resonance imaging (MRI) were performed. Multiple linear regression analyses were performed. RESULTS: Lower retinal capillary perfusion was correlated with worse Oral Symbol Digit Test (P < = 0.005) and Fluid Cognition Composite scores (P < = 0.02), but not with the Crystallized Cognition Composite score (P > = 0.41). Lower retinal perfusion was also correlated with higher free water and peak width of skeletonized mean diffusivity, and lower fractional anisotropy (all P < 0.05) on MRI (N = 35). DISCUSSION: Lower retinal capillary perfusion is associated with worse information processing, fluid cognition, and MRI biomarkers of cerebral small vessel disease, but is not related to crystallized cognition.

Deletion of aquaporin-4 improves capillary blood flow distribution in brain edema.

Brain edema is a feared complication to disorders and insults affecting the brain. It can be fatal if the increase in intracranial pressure is sufficiently large to cause brain herniation. Moreover, accruing evidence suggests that even slight elevations of intracranial pressure have adverse effects, for instance on brain perfusion. The water channel aquaporin-4 (AQP4), densely expressed in perivascular astrocytic endfeet, plays a key role in brain edema formation. Using two-photon microscopy, we have studied AQP4-mediated swelling of astrocytes affects capillary blood flow and intracranial pressure (ICP) in unanesthetized mice using a mild brain edema model. We found improved regulation of capillary blood flow in mice devoid of AQP4, independently of the severity of ICP increase. Furthermore, we found brisk AQP4-dependent astrocytic Ca2+ signals in perivascular endfeet during edema that may play a role in the perturbed capillary blood flow dynamics. The study suggests that astrocytic endfoot swelling and pathological signaling disrupts microvascular flow regulation during brain edema formation.

Point of care assay for blood aripiprazole concentrations: development, validation and utility.

BACKGROUND: The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis. AIMS: To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole. METHOD: Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method. RESULTS: A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml). CONCLUSIONS: The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

Self-sampling of blood using a topper and pediatric tubes; a prospective feasibility study for PSA analysis using 120 prostate cancer patients.

OBJECTIVES: Self-collection of blood for diagnostic purposes by blood collection assist devices (BCAD) has gained a lot of momentum. Nonetheless, there are a lack of studies demonstrating the feasibility and reliability of self-collecting capillary blood for routine (immuno)chemistry testing. In this study we describe the topper technology together with pediatric tubes to enable self-collection of blood and investigated its feasibility for PSA testing by prostate cancer patients. METHODS: A total of 120 prostate cancer patients for which a routine follow-up PSA test was requested, were included in this study. Patients received instruction materials and the blood-collection device consisting of a topper, pediatric tube and base-part, and performed the blood collection procedure themselves. Afterwards a questionnaire was filled-in. Finally, PSA was measured on a Roche Cobas Pro. RESULTS: The overall self-sampling success rate was 86.7 %. Furthermore, when specified per age category, a 94.7 % success rate for patients under 70 years and a 25 % success rate for patients of 80 years and older was observed. Venous and self-collected PSA were highly comparable when analyzed by Passing-Bablok regression with a slope of 0.99 and intercept of 0.00011, Spearmans correlation coefficient (0.998) and average self-collected PSA recovery of 99.8 %. CONCLUSIONS: Evidence is presented that self-collected capillary blood by topper and pediatric tube from the finger is feasible, particularly for patients under 70 years. Furthermore, capillary blood self-sampling did not compromise any of the PSA test results. Future validation in a real-world setting, without supervision and including sample stability and logistics, is required.

Validation of the Hem-Col capillary blood collection system for routine laboratory analyses.

At home collection of capillary blood using Hem-Col tubes (Labonovum) could offer a solution to patients with chronic conditions, who require frequent laboratory analyses. The collection tubes contain a conservation buffer to stabilize analytes for up to 5 days. In this validation study it was investigated whether analytes are measured accurately in Hem-Col tubes 5 days after collection. Forty-six healthy volunteers donated blood via venepuncture as well as capillary blood by finger prick using Hem-Col tubes. The analytes were measured within 2 h for the venepuncture and after 120 h for the Hem-Col method. The results of each analyte were analysed using Passing-Bablok regression analyses. The analytes that met the predefined acceptance criteria were total cholesterol, LDL-cholesterol, thyroid stimulating hormone (TSH) and glycated haemoglobin (HbA1c). HDL-cholesterol, C-reactive protein (CRP), ferritin, bilirubin total, creatinine, gGT and triglycerides met two out of three acceptance criteria. All other analytes did not meet the predefined criteria. The Hem-Col method is suitable for the measurement of total cholesterol, LDL-cholesterol, thyroid stimulating hormone (TSH) and glycated haemoglobin (HbA1c). However, due to this limited set of valid tests and practical limitations, routine application of this novel collection system in daily practice is limited.

Does the age of packed red blood cells, donor sex or sex mismatch affect the sublingual microcirculation in critically ill intensive care unit patients? A secondary interpretation of a retrospective analysis.

In vitro studies have thoroughly documented age-dependent impact of storage lesions in packed red blood cells (pRBC) on erythrocyte oxygen carrying capacity. While studies have examined the effect of pRBC age on patient outcome only few data exist on the microcirculation as their primary site of action. In this secondary analysis we examined the relationship between age of pRBC and changes of microcirculatory flow (MCF) in 54 patients based on data from the Basel Bedside assessment Microcirculation Transfusion Limit study (Ba2MiTraL) on effects of pRBC on sublingual MCF. Mean change from pre- to post-transfusion proportion of perfused vessels (∆PPV) was + 8.8% (IQR - 0.5 to 22.5), 5.5% (IQR 0.1 to 10.1), and + 4.7% (IQR - 2.1 to 6.5) after transfusion of fresh (≤ 14 days old), medium (15 to 34 days old), and old (≥ 35 days old) pRBC, respectively. Values for the microcirculatory flow index (MFI) were + 0.22 (IQR - 0.1 to 0.6), + 0.22 (IQR 0.0 to 0.3), and + 0.06 (IQR - 0.1 to 0.3) for the fresh, medium, and old pRBC age groups, respectively. Lower ∆PPV and transfusion of older blood correlated with a higher Sequential Organ Failure Assessment (SOFA) score of patients upon admission to the intensive care unit (ICU) (p = 0.01). However, regression models showed no overall significant correlation between pRBC age and ∆PPV (p = 0.2). Donor or recipient sex had no influence. We detected no significant effect of pRBC on microcirculation. Patients with a higher SOFA score upon ICU admission might experience a negative effect on the ∆PPV after transfusion of older blood.

A head-to-head comparison between Guardian Connect and FreeStyle Libre systems and an evaluation of user acceptability of sensors in patients with type 1 diabetes.

AIMS: A user-calibrated real-time continuous glucose monitoring (rt-CGM) system is compared to a factory-calibrated flash glucose monitoring (FGM) system and assessed in terms of accuracy and acceptability in patients with type 1 diabetes (T1D). METHODS: Ten participants with T1D were enroled from a specialist diabetes centre in Singapore and provided with the Guardian Connect with Enlite Sensor (Medtronic, Northridge, CA, USA) and first-generation Freestyle Libre System (Abbott Diabetes Care, Witney, UK), worn simultaneously. Participants had to check capillary blood glucose four times per day. At the end of week 1 and week 2, participants returned for data download and were given a user evaluation survey. RESULTS: Accuracy evaluation between Guardian Connect and Freestyle Libre includes the overall mean absolute relative difference value (9.7 ± 11.0% vs. 17.5 ± 10.9%), Clarke Error Grid zones A + B (98.6% vs. 98.1%), sensitivity (78.9% vs. 63.4%), and specificity (93.4% vs. 81.0%). Notably, time below range (<3.9 mmol/L) was 10.5% for FGM versus 2% for rt-CGM. From the evaluation survey, 90% of participants perceived rt-CGM to be accurate versus 40% for FGM, although the majority found both devices to be easy to use, educational, and useful in improving glycaemic control. However, due to the cost of sensors, only 30% were keen to use either device for continuous monitoring. CONCLUSIONS: Although rt-CGM was superior to FGM in terms of accuracy, the value of glucose trends in both devices is still useful in diabetes self-management. Patients and clinicians may consider either technology depending on their requirements.

Point-of-care Hb measurement in pooled capillary blood by a portable autoanalyser: comparison with venous blood Hb measured by reference methods in cross-sectional and longitudinal studies.

Population-based surveys commonly use point-of-care (POC) methods with capillary blood samples for estimating Hb concentrations; these estimates need to be validated by comparison with reference methods using venous blood. In a cross-sectional study in 748 participants (17-86 years, 708 women, Hb: 5·1 to 18·2 g/dl) from Hyderabad, India, we validated Hb measured from a pooled capillary blood sample by a POC autoanalyser (Horiba ABX Micros 60OT, Hb-C-AA) by comparison with venous blood Hb measured by two reference methods: POC autoanalyser (Hb-V-AA) and cyanmethemoglobin method (Hb-V-CM). These comparisons also allowed estimation of blood sample-related and equipment-related differences in the Hb estimates. We also conducted a longitudinal study in 426 participants (17-21 years) to measure differences in the Hb response to iron folate (IFA) treatment by the capillary blood POC method compared with the reference methods. In the cross-sectional study, Bland-Altman analyses showed trivial differences between source of blood (Hb-C-AA and Hb-V-AA; mean difference, limits of agreement: 0·1, -0·8 to 1·0 g/dl) and between analytical methods (Hb-V-AA and Hb-V-CM; mean difference, limits of agreement: < 0·1, -1·8 to 1·8 g/dl). Cross-sectional anaemia prevalence estimated using Hb-C-AA did not differ significantly from Hb-V-CM or Hb-V-AA. In the longitudinal study, the Hb increment in response to IFA intervention was not different when using Hb-C-AA (1·6 ± 1·7 g/dl) compared with Hb-V-AA (1·7 ± 1·7 g/dl) and Hb-V-CM (1·7 ± 1·7 g/dl). The pooled capillary blood-autoanalyzer method (Hb-C-AA) offers a practical and accurate way forward for POC screening of anaemia.

Accounting for arterial and capillary blood gases for calculation of cerebral blood flow in preterm infants.

One of the most feared neurological complications of premature birth is intraventricular hemorrhage, frequently triggered by fluctuations in cerebral blood flow (CBF). Although several techniques for CBF measurement have been developed, they are not part of clinical routine in neonatal intensive care. A promising tool for monitoring of CBF is its numerical assessment using standard clinical parameters such as mean arterial pressure, carbon dioxide partial pressure (pCO2) and oxygen partial pressure (pO2). A standard blood gas analysis is performed on arterial blood. In neonates, capillary blood is widely used for analysis of blood gas parameters. The purpose of this study was the assessment of differences between arterial and capillary analysis of blood gases and adjustment of the mathematical model for CBF calculation to capillary values. The statistical analysis of pCO2 and pO2 values collected from 254 preterm infants with a gestational age of 23-30 weeks revealed no significant differences between arterial and capillary pCO2 and significantly lower values for capillary pO2. The estimated mean differences between arterial and capillary pO2 of 15.15 mmHg (2.02 kPa) resulted in a significantly higher CBF calculated for capillary pO2 compared to CBF calculated for arterial pO2. Two methods for correction of capillary pO2 were proposed and compared, one based on the mean difference and another one based on a regression model. CONCLUSION: Capillary blood gas analysis with correction for pO2 as proposed in the present work is an acceptable alternative to arterial sampling for the assessment of CBF. WHAT IS KNOWN: • Arterial blood analysis is the gold standard in clinical practice. However, capillary blood is widely used for estimating blood gas parameters. • There is no significant difference between the arterial and capillary pCO2 values, but the capillary pO2 differs significantly from the arterial one. WHAT IS NEW: • The lower capillary pO2 values yield significantly higher values of calculated CBF compared to CBF computed from arterial pO2 measurements. • Two correction methods for the adjustment of capillary pO2 to arterial pO2 that made the difference in the calculated CBF insignificant have been proposed.

Mathematical Arterialization of Capillary Blood for Blood Gas Analysis in Critically Ill Patients.

BACKGROUND: In clinical practice, capillary blood taken from hyperemized earlobes (CBGE) or fingertips (CBGF) is frequently used as substitute for arterial blood (ABG) for blood gas analysis. While there is a close agreement between ABG and CBGE/CBGF regarding pH and pCO2, pO2 is often underestimated by CBG. Recently, a software tool (v-TAC®; Roche Diagnostics, Risch-Rotkreuz, Switzerland) has been developed to calculate ABG values based on a peripheral venous blood gas analysis supplemented with peripheral oxygen saturation. OBJECTIVE: Here we investigate whether v-TAC can also be used to calculate ABG values from capillary blood samples. METHODS: Patients (n = 85) with an indwelling arterial line were included in the study. A reference ABG sample (ABG1) was obtained, followed by CBGE, CBGF, and finally a second ABG (ABG2). Results of CBGE/CBGF before and after mathematical arterialization by v-TAC (aCBGE/aCBGF) were compared to ABG1. RESULTS: After mathematical arterialization by v-TAC, the mean bias in pO2 between ABG1 and CBGE went down from 5.24 mm Hg (95% limit of agreement [95% LoA]: -14.19 to 24.67) to 0.18 mm Hg (95% LoA: -11.84 to 12.20) and was in a similar range as the mean bias between ABG1 and ABG2 (0.39 mm Hg [95% LoA: -13.46 to 14.24]). Differences in pH and pCO2 between arterial and capillary samples were small before and after mathematical arterialization. Very similar results were obtained when using fingertip instead of earlobe capillary blood. CONCLUSION: In summary, v-TAC can be used for mathematical arterialization of capillary blood samples for blood gas analysis resulting in increased diagnostic accuracy for pO2.

Agreement of blood glucose measured with glucose meter in arterial, central venous, and capillary samples in adult critically ill patients.

BACKGROUND: The measurement of blood glucose in critically ill patients is still performed in many ICUs with glucose meters and capillary samples. Several prevalent factors in these patients affect the accuracy of the results and should be interpreted with caution. A weak recommendation from the Surviving Sepsis Campaign (SSC) suggests the use of arterial blood rather than capillary blood for point of care testing using glucose meters. AIMS AND OBJECTIVES: To analyse the agreement between arterial, central venous, and capillary blood samples of glucose values measured by glucose meter in critically ill patients and study potential confounding factors. DESIGN: Prospective cross-sectional study in a general intensive care unit (ICU). Patients needing insulin treatment (subcutaneous or intravenous) and blood glucose control were included. METHODS: Standardized collection of blood samples and measurement of glucose values with a glucometer. Agreement was studied by the Bland-Altman method and stratified analysis of disagreement-survival plots was used to study the influence of haematocrit, pH range, SOFA score, capillary refilling time, intravenous insulin infusion, and lactic acid. RESULTS: A total of 297 measurements from 54 patients were included. The mean arterial blood glucose was 150.42 (range 31-345 mg/dL). In the graphical analysis, there is a poor agreement both in capillary and venous central to arterial samples, but in opposite direction (underestimation of capillary and overestimation of central venous). Factors associated with a reduction in the agreement between arterial and capillary samples were elevated lactate, poor capillary refilling, and hemodynamic failure. Patients without hemodynamic compromise have an acceptable agreement with values for absolute differences of 16 mg/dL for a disagreement of 10%. CONCLUSIONS: In critically ill patients, the measurement of blood glucose with a glucose meter should be performed with arterial samples whenever possible. Capillary samples do not accurately estimate arterial blood glucose values in patients with shock and/or vasoactive drugs and underestimate the values in the range of hypoglycemia. Venous samples are subject to error because of potential contamination. RELEVANCE TO CLINICAL PRACTICE: This study adds support to the recommendation of using arterial blood rather than capillary or venous blood when using glucose meters in critically ill patients, especially in those with hemodynamic failure.

Creatine and creatinine quantification in olympic athletes: dried blood spot analysis pilot study.

Capillary dried blood spot (DBS) samples facilitate field-based collection without venipuncture. This pilot study aims to evaluate the viability of creatine (Cr) and creatinine (Crt) quantification using fresh capillary serum (CrS/CrtS) and DBS samples (CrDBS/CrtDBS), using Flow Injection Analysis Mass Spectrometry (FIA - MS). Nine Olympic Athletes provided a capillary blood sample to assess CrS/CrtS and CrDBS/CrtDBS quantified by FIA - MS. No difference between CrtS (mean ± SD: 813.6 ± 102.4 µmol/L) and CrtDBS (812.4 ± 108.1 µmol/L) was observed with acceptable variance [SEM 88.7; CV 10.7%; ICC 0.57 (CI 95% 0.06 - 0.84)] and agreement [very strong (Spearman: r = 0.77; p < 0.01) or strong (Pearson: r = 0.56; p = 0.04); Bland Altman: lower (-193) and upper (+196) limits of agreement]. CrS (mean ± SD: 691.8 ± 165.2 µmol/L) was significantly different to CrDBS (2911 ± 571.4 µmol/L) with unacceptable variance [SEM 171.6; CV 27%; ICC 0.002 (CI 95% -0.02 - 0.07)] and 'weak' agreement [Spearman: r = 0.21, p = 0.47 and Pearson: r = 0.06, p = 0.84; Bland Altman lower (-3367) and upper (-1072) limits of agreement]. Crt quantification is viable using both CrtS and CrtDBS (but not for Cr and CrS/CrDBS), with the DBS tissue handling technique offering several methodological and practice facing advantages. Future work should expand upon the sample size, explore sport/discipline relevant analytes across a full competitive season, including key training, recovery and performance blocks of their periodized performance plan.

URGENT 1.5: diagnostic accuracy of the modified HEART score, with fingerstick point-of-care troponin testing, in ruling out acute coronary syndrome.

BACKGROUND: The HEART score is a validated risk stratification tool for chest pain patients presenting to the emergency department and was recently investigated for implementation in a pre-hospital setting. Fingerstick (capillary blood) point-of-care (POC) troponin testing enables quick measurements outside the hospital and seems easier to implement than the current venous blood sampling techniques. This study investigates the diagnostic accuracy of the modified HEART score, integrating fingerstick POC troponin testing, in ruling out acute coronary syndrome (ACS). METHODS: The data of 96 patients with chest pain, included in a study investigating a novel POC troponin device under development at the cardiac emergency department, were analysed retrospectively. Based on the patients' admission data and capillary POC high-sensitivity troponin I (hs-cTnI) results, the modified HEART score was determined. The outcome measure, for evaluating the diagnostic accuracy of the modified HEART score, was the occurrence of ACS. RESULTS: Of the total study population, 33 patients (34%) were diagnosed with ACS. Seventeen patients (18%) were classified as low risk (0-3 points) and one patient (6%) in this group was diagnosed with ACS. The sensitivity and negative predictive value of the modified HEART score was 97.0 and 97.6%, respectively. CONCLUSION: The modified HEART score, integrating capillary POC hs-cTnI results, is a promising tool for ruling out ACS in patients with chest pain presenting to the cardiac emergency department. These results encourage prospective investigation into the integration of fingerstick POC troponin testing in the modified HEART score in a pre-hospital setting.

ATP induces contraction of cultured brain capillary pericytes via activation of P2Y-type purinergic receptors.

Brain capillary pericytes have been suggested to play a role in the regulation of cerebral blood flow under physiological and pathophysiological conditions. ATP has been shown to cause constriction of capillaries under ischemic conditions and suggested to be involved in the "no-reflow" phenomenon. To investigate the effects of extracellular ATP on pericyte cell contraction, we studied purinergic receptor activation of cultured bovine brain capillary pericytes. We measured intracellular Ca2+ concentration ([Ca2+]i) responses to purinergic agonists with the fluorescent indicators fura-2 and Cal-520 and estimated contraction of pericytes as relative change in cell area, using real-time confocal imaging. Addition of ATP caused an increase in cytosolic calcium and contraction of the brain capillary pericytes, both reversible and inhibited by the purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Furthermore, we demonstrated that ATP-induced contraction could be eliminated by intracellular calcium chelation with BAPTA, indicating that the contraction was mediated via purinergic P2-type receptor-mediated [Ca2+]i signaling. ATP stimulation induced inositol triphosphate signaling, consistent with the notion of P2Y receptor activation. Receptor profiling studies demonstrated the presence of P2Y1 and P2Y2 receptors, using ATP, UTP, ADP, and the subtype specific agonists MRS2365 (P2Y1) and 2-thio-UTP (P2Y2). Addition of specific P2X agonists only caused an [Ca2+]i increase at high concentrations, attributed to activation of inositol triphosphate signaling. Our results suggest that contraction of brain capillary pericytes in vitro by activation of P2Y-type purinergic receptors is caused by intracellular calcium release. This adds more mechanistic understanding of the role of pericytes in vessel constriction and points toward P2Y receptors as potential therapeutic targets.NEW & NOTEWORTHY The study concerns brain capillary pericytes, which have been suggested to play a role in the regulation of cerebral blood flow. We show that extracellular ATP causes contraction of primary brain pericytes by stimulation of purinergic receptors and subsequent release of intracellular Ca2+ concentration ([Ca2+]i). The contraction is mainly mediated through activation of P2Y-receptor subtypes, including P2Y1 and P2Y2. These findings add more mechanistic understanding of the role of pericytes in regulation of capillary blood flow. ATP was earlier suggested to be involved in capillary constriction in brain pathologies, and our study gives a detailed account of a part of this important mechanism.

Development and validation of a novel microfluidic device for the manipulation of skeletal muscle microvascular blood flow in vivo.

OBJECTIVE: To develop and validate a novel liquid microfluidic approach to deliver drugs to microscale regions of tissue while simultaneously allowing for visualization and quantification of microvascular blood flow. METHODS: Microfluidic devices were fabricated using soft lithographic techniques, molded in polydimethylsiloxane, and bound to a coverslip with a 600 × 300 µm micro-outlet. Sprague-Dawley rats, anesthetized with pentobarbital, were instrumented to monitor systemic parameters. The extensor digitorum longus muscle was dissected, externalized, and reflected across the device mounted on the stage of an inverted microscope. Doses (10-8 to 10-3  M) of adenosine triphosphate (ATP), acetylcholine, and phenylephrine (PE) were administered to the muscle via perfusion through the device. Microvascular blood flow directly overlying the micro-outlet was recorded at multiple focal depths. Red blood cell (RBC) velocity, supply rate, and hematocrit were measured from recordings. RESULTS: ATP significantly increased RBC velocity and supply rate. Increasing concentrations of PE caused a decrease in RBC velocity and supply rate. Perfusion changes were restricted to areas directly overlying the micro-outlet and within 500 µm. CONCLUSIONS: This novel microfluidic device allows for a controlled delivery of dissolved substances to constrained regions of microvasculature while simultaneously allowing for visualization and measurement of blood flow within discrete vessels and networks.

Reference values of retinal microcirculation parameters derived from a population random sample.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Our objective has been to establish reference values for major functional and structural parameters of retinal microcirculation in a randomly selected urban population sample. A total of 398 randomly selected individuals from an urban population aged 25 to 65 years, resident in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry (SLDF), with data evaluable in 343 patients. Of this number, complete data were available for 256 individuals free from manifest cardiovascular disease, diabetes and drug treatment for hypertension and/or dyslipidemia, constituting the reference value population. Juxtapapillary retinal capillary blood flow has increased significantly with age whereas vessel and luminal diameters have decreased. No sex differences in retinal microcirculation parameters have been found. Therefore, reference values for retinal microcirculation parameters have been established by age groups. Unattended automated office systolic BP, after adjusting for age, correlated significantly with wall-to-lumen ratio (WLR) and wall thickness (WT). Moreover, after adjusting for age and mean BP, a positive relationship has been found between carotid femoral pulse wave velocity and WT, WLR and wall cross-sectional area, indicating the interaction between micro- and macro-vasculature. In conclusion, our study is the first to provide reference values of retinal microcirculation parameters in a random Caucasian population sample. Our results have shown that, at the population level, the first structural changes in retinal microcirculation are those in lumen diameters. Of note, a close relationship between BP and vascular remodeling of retinal arterioles and between aortic stiffness and WLR of retinal arterioles suggests an interaction between micro- and macro-vasculature.

Comparison between a laser lancing device and lancet for capillary blood sampling, capillary blood hemoglobin measurement, and blood typing.

BACKGROUND: Blood donor screening includes tests using capillary blood, which is usually obtained by finger pricking using a lancet; however, the lancet has some shortcomings, such as skin puncture pain and needle stick injury. Recently, laser lancing devices for finger-prick sampling have been developed. We compared capillary blood Hb (cHb) levels and blood typing results obtained using a laser lancing device with those obtained using a lancet. STUDY DESIGN AND METHODS: cHb levels, blood typing results, and skin puncture pain scores were assessed in 191 participants. Finger-prick sampling was performed using LMT-1000 (LaMeditech, Seoul, Korea) and a lancet on the same finger on different hands. Paired venous Hb (vHb) levels were assessed in 103 participants using an automated hematology analyzer and compared with the cHb levels obtained using both lancing devices. RESULTS: The paired cHb results obtained with the laser lancing device and lancet showed a strong correlation (r = 0.927, p < .001) without any significant difference (p = .113) and a substantial agreement (κ = 0.654) for the identification of participants with a low Hb level (<12.5 g/dl). cHb levels were significantly higher than vHb levels with both lancing devices (mean differences: 0.27-0.43 g/dl). The results of blood typing using the laser lancing device showed 100% accuracy. Use of the laser lancing device showed significantly lower skin puncture pain scores (p < .001). CONCLUSION: Use of a laser lancing device for capillary Hb measurement and blood typing showed accurate results, with significantly reduced skin puncture pain. Laser lancing devices could be feasible for donor screening tests.