QFT-Plus: a plus in variability? - Evaluation of new generation IGRA in serial testing of students with a migration background in Germany.

BACKGROUND: Currently available Interferon-gamma release assays (IGRAs) show a considerable variability in serial testing for latent tuberculosis infection (LTBI). This study offers first results for the new generation IGRA QuantiFERON-TB Gold Plus (QFT-Plus) introduced in 2015 in comparison with its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT) from serial testing of students with a migration background at German universities. METHODS: Forty-one students were selected from a previous study. All students with a positive IGRA were asked and 11 agreed to participate in this cohort study. Additionally 30 students with negative IGRA results were selected by chance. Weekly testing with QFT-Plus and QFT-GIT was performed in all individuals over a 4-week period. IGRA variability was evaluated by calculating conversion and reversion rates. RESULTS: From 41 participants a total number of 163 serial measurements were analyzed for each IGRA, leading to 122 possible IGRA changes each. QFT-Plus had four conversions and two reversions leading to a conversion rate of 4.3% (4 of 93 possible conversions, 95% CI 1.4-11.3%) and reversion rate of 6.9% (2 of 29 possible reversions, 95% CI 1.2-24.2%). QFT-GIT had 2 conversions and 1 reversion causing slightly lower rates with 2.2% conversions (2 of 91, 95% CI 0.4-8.5%) and 3.2% reversions (1 of 31, 95% CI 0.2-18.5%). Inconsistent IGRA results occurred in 4 subjects for QFT-Plus (8 stable positives, 29 stable negatives) and in 2 subjects for QFT-GIT (9 stable positives, 30 stable negatives). Agreement between the two IGRAs was 95.1% (κ = 0.89). Variance attributed to the individuals was low (QFT-Plus: ICC = 0.88). CONCLUSION: This study confirms occurrence of conversions and reversions for the new QFT-Plus in serial testing of a high-risk cohort in a low-incidence setting with improbable new TB contact during the study. QFT-Plus conversion and reversion rates were slightly higher than for the QFT-GIT but overall they were lower for both IGRAs than in other studies that investigated IGRA variability.

Variations of heart rate variability parameters prior to the onset of ventricular tachyarrhythmia and sinus tachycardia in ICD patients. Results from the heart rate variability analysis with automated ICDs (HAWAI) registry.

The HAWAI registry evaluated the role of heart rate variability in predicting the occurrence of ventricular tachycardia and fibrillation (VT/VF) and sinus tachycardia in patients with an implantable cardioverter-defibrillator (45 patients with 155 RR recordings). A significant decrease of the mean value of all RR intervals (MeanNN) was observed in the period starting 20 and 40 min prior to VT/VF and sinus tachycardia, respectively. The standard deviation of RR intervals (SDNN) and the power at low frequency (LF) were the only parameters with significant changes prior to VT/VF. For sinus tachycardia, the root mean square of successive differences of all successive RR intervals (r-MSSD) and the power at low and high frequency (HF) decreased, whereas SDNN and the power at very low frequency increased. Comparison of RR recordings preceding VT/VF and sinus tachycardia revealed significant differences of the MeanNN, SDNN, r-MSSD, LF and HF. Based on a classification and regression tree analysis, MeanNN, SDNN and r-MSSD showed a sensitivity of 94.4% and a specificity of 50.6% as predictors of VT/VF. Our results suggest that the temporal changes in heart rate before an arrhythmic event can be used to predict the occurrence of VT/VF. These parameters may be used to optimize pacing therapies designed to prevent VT/VF recurrences as well as for improving device-based discriminators for VT/VF and sinus tachycardia.

Changes in sevoflurane plasma concentration with delivery through the oxygenator during on-pump cardiac surgery.

BACKGROUND: It is unclear what factors affect the uptake of sevoflurane administered through the membrane oxygenator during cardiopulmonary bypass (CPB) and whether this can be monitored via the oxygenator exhaust gas. METHODS: Stable delivery of sevoflurane was administered to 30 elective cardiac surgery patients at 1.8 vol% (inspiratory) via the anaesthetic circuit and ventilator. During CPB, sevoflurane was administered in the oxygenator fresh gas supply (Compactflo Evolution™; Sorin Group, Milano, Italy). Sevoflurane plasma concentration (SPC) was measured using gas chromatography. Changes were correlated with bispectral index (BIS), patient temperature, haematocrit, plasma albumin concentration, oxygenator fresh gas flow, and the sevoflurane concentration in the oxygenator exhaust at predefined time points. RESULTS: The mean SPC pre-bypass was 54.9 µg ml(-1) [95% confidence interval (CI): 50.6-59.1]. SPC decreased to 43.2 µg ml(-1) (95% CI: 40.3-46.1; P<0.001) after initiation of CPB, and was lower still during rewarming and weaning from bypass, 39.4 µg ml(-1) (95% CI: 36.6-42.3; P<0.001). BIS did not exceed a value of 55. SPCs were higher during hypothermia (P<0.001) and with an increase in oxygenator fresh gas flow (P=0.015), and lower with haemodilution (P=0.027). No correlation was found between SPC and the concentration of sevoflurane in the oxygenator exhaust gas (r=-0.04; 95% CI: -0.18 to 0.09; P=0.53). CONCLUSIONS: The uptake of sevoflurane delivered via the membrane oxygenator during CPB seems to be affected by hypothermia, haemodilution, and changes in the oxygenator fresh gas supply flow. Measuring the concentration of sevoflurane in the exhaust from the oxygenator is not useful for monitoring sevoflurane administration during bypass.

Validation of cord blood split products prepared by an automated method.

OBJECTIVES: In this study, we studied whether the contents of the two compartments of automatically processed cord blood (CB) units are comparable with respect to cell counts and viability and therefore suitable for clinical therapy. BACKGROUND: CB-derived stem cells are increasingly used for allogeneic transplantation. Many centres prepare the transplants by automated methods allowing to split the product into two portions. METHODS: CB was collected at different sites in Germany and transported to a single centre for processing. Before and after cryopreservation laboratory analyses were performed to compare the quality of the two CB segments. RESULTS: In total, 33 products were processed [mean collection volume: 18·6 ± 1·2 mL (range 15·2-20·2 mL) segment A; mean: 4·7 ± 0·3 mL (range 4·2-5·2 mL) segment B]. CD34+ cell counts, viability of CD34+ cells and many other haematological parameters showed a good comparibility between the two segments. However, lymphocyte counts and results of clonogenic assays were significantly different between the two segments of the split product. CONCLUSION: We conclude that the preparation of the cord blood unit by the automated process results in a homogenous distribution of stem and progenitor cells. However, our findings show that the clonogenic capacity differs between the two segments.

Automated, semi-automated, and manual analyses of anti-cardiolipin and anti-ß2-glycoprotein I antibodies in women with a history of miscarriage.

INTRODUCTION: Anti-cardiolipin and ß2-glycoprotein I antibodies represent important diagnostic parameters in routine hematology. In this study, five different automated, semi-automated, and manual immunoassays detecting IgG/IgM anti-cardiolipin and anti-ß2 -glycoprotein I antibodies were tested. METHODS: A total of 162 samples from women with a history of miscarriage were recruited from 110 different G&O outpatient centers in Germany. RESULTS: For both anti-cardiolipin and anti-ß2 -glycoprotein I antibodies, considerable differences in the percentage of positive results were seen between all five methods, and itemization of all positive test results revealed a poor accordance. These findings were confirmed by Cohen's kappa coefficients. CONCLUSION: Our study revealed a moderate to poor accordance between five different test systems for anti-cardiolipin and anti-ß2 -glycoprotein I antibodies. Such deviations may result in clinical misinterpretation of data and may lead to wrong therapeutic consequences. Therefore, further standardization of all tests for anti-phospholipid antibodies should be achieved.

Expression levels of Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) in primary breast carcinoma and distant breast cancer metastases.

INTRODUCTION: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) gained increasing attention regarding tumorprogression and metastatic spread in breast cancer. The aim of this study was to examine ALCAM expression levels in primary breast cancer and distant metastases of the same patient within 29 autopsy cases to better understand the underlying mechanisms of metastases and the role of adhesion molecules in this process. MATERIAL AND METHODS: Paraffin-embedded tissue of the primary and distant metastases (N=84) were collected and ALCAM immunohistochemistry was performed. RESULTS: The primary tumor and all metastases showed a statistically normally distributed ALCAM expression. ALCAM expression level average differs between immunoreactive score (IRS) (mean) 4.16 (lung)-5.00 (adrenal gland). Of the metastatic ALCAM expression levels we obtained an intra-class correlation (ICC) of 80.9%, indicating a strong cluster effect of measurements in the same patient. ALCAM expression scores in metastatic sites and in the primary analyzed by hierarchical regression analysis showed that ALCAM expression in the primary is prognostic for ALCAM expression in all different sites of metastases (slope=0.773, p < 0.001, r(2)= 0.504). CONCLUSION: ALCAM expression in the primary is positively correlated to ALCAM expression in metastases within one single patient. This could show a tumorbiological context of ALCAM for the development of metastases in breast cancer.