Current T1 and T2 mapping techniques applied with simple thresholds cannot discriminate acute from chronic myocadial infarction on an individual patient basis: a pilot study.

BACKGROUND: Studying T1- and T2-mapping for discrimination of acute from chronic myocardial infarction (AMI, CMI). METHODS: Eight patients with AMI underwent CMR at 3 T acutely and after >3 months. Imaging techniques included: T2-weighted imaging, late enhancement (LGE), T2-mapping, native and post-contrast T1-mapping. Myocardial T2- and T1-relaxation times were determined for every voxel. Abnormal voxels as defined by having T2- and T1-values beyond a predefined threshold (T2 > 50 ms, native T1 > 1250 ms and post-contrast T1 < 350 ms) were highlighted and compared with LGE as the reference. RESULTS: Abnormal T2-relaxation times were present in the voxels with AMI (=> delete acute infarction; unfortunately this is not possible in your web interface) acute infarction only in half of the subjects. Abnormal T2-values were also present in subjects with CMI, thereby matching the chronically infarcted territory in some. Abnormal native T1 times were present in voxels with AMI in 5/8 subjects, but also remote from the infarcted territory in four. In CMI, abnormal native T1 values corresponded with infarcted voxels, but were also abnormal remote from the infarcted territory. Voxels with abnormal post-contrast T1-relaxation times agreed well with LGE in AMI and CMI. CONCLUSIONS: In this pilot-study, T2- and T1-mapping with simple thresholds did not facilitate the discrimination of AMI and CMI.

Prospective, randomized comparison of gadopentetate and gadobutrol to assess chronic myocardial infarction applying cardiovascular magnetic resonance.

BACKGROUND: We hypothesized that the contrast medium gadobutrol is not inferior compared to Gd-DTPA in identifying and quantifying ischemic late gadolinium enhancement (LGE), even by using a lower dose. METHODS: We prospectively enrolled 30 patients with chronic myocardial infarction as visualized by LGE during clinical routine scan at 1.5 T with 0.20 mmol/kg Gd-DTPA. Participants were randomized to either 0.15 mmol/kg gadobutrol (group A) or 0.10 mmol/kg gadobutrol (group B). CMR protocol was identical in both exams. LGE was quantified using a semiautomatic approach. Signal intensities of scar, remote myocardium, blood and air were measured. Signal to noise (SNR) and contrast to noise ratios (CNR) were calculated. RESULTS: Signal intensities were not different between Gd-DTPA and gadobutrol in group A, whereas significant differences were detected in group B. SNR of injured myocardium (53.5+/-21.4 vs. 30.1+/-10.4, p = 0.0001) and CNR between injured and remote myocardium (50.3+/-20.3 vs. 27.3+/-9.3, p < 0.0001) were lower in gadobutrol. Infarct size was lower in both gadobutrol groups compared to Gd-DTPA (group A: 16.8+/-10.2 g vs. 12.8+/-6.8 g, p = 0.03; group B: 18.6+/-12.0 g vs. 14.0+/-9.9 g, p = 0.0016). CONCLUSIONS: Taking application of 0.2 mmol/kg Gd-DTPA as the reference, the delineation of infarct scar was similar with 0.15 mmol/kg gadobutrol, whereas the use 0.10 mmol/kg gadobutrol led to reduced tissue contrast. TRIAL REGISTRATION: The study had been registered under EudraCT Number: 2010-020775-22. Registration date: 2010.08.10.

Analysis of Documentation Speed Using Web-Based Medical Speech Recognition Technology: Randomized Controlled Trial.

BACKGROUND: Clinical documentation has undergone a change due to the usage of electronic health records. The core element is to capture clinical findings and document therapy electronically. Health care personnel spend a significant portion of their time on the computer. Alternatives to self-typing, such as speech recognition, are currently believed to increase documentation efficiency and quality, as well as satisfaction of health professionals while accomplishing clinical documentation, but few studies in this area have been published to date. OBJECTIVE: This study describes the effects of using a Web-based medical speech recognition system for clinical documentation in a university hospital on (1) documentation speed, (2) document length, and (3) physician satisfaction. METHODS: Reports of 28 physicians were randomized to be created with (intervention) or without (control) the assistance of a Web-based system of medical automatic speech recognition (ASR) in the German language. The documentation was entered into a browser's text area and the time to complete the documentation including all necessary corrections, correction effort, number of characters, and mood of participant were stored in a database. The underlying time comprised text entering, text correction, and finalization of the documentation event. Participants self-assessed their moods on a scale of 1-3 (1=good, 2=moderate, 3=bad). Statistical analysis was done using permutation tests. RESULTS: The number of clinical reports eligible for further analysis stood at 1455. Out of 1455 reports, 718 (49.35%) were assisted by ASR and 737 (50.65%) were not assisted by ASR. Average documentation speed without ASR was 173 (SD 101) characters per minute, while it was 217 (SD 120) characters per minute using ASR. The overall increase in documentation speed through Web-based ASR assistance was 26% (P=.04). Participants documented an average of 356 (SD 388) characters per report when not assisted by ASR and 649 (SD 561) characters per report when assisted by ASR. Participants' average mood rating was 1.3 (SD 0.6) using ASR assistance compared to 1.6 (SD 0.7) without ASR assistance (P<.001). CONCLUSIONS: We conclude that medical documentation with the assistance of Web-based speech recognition leads to an increase in documentation speed, document length, and participant mood when compared to self-typing. Speech recognition is a meaningful and effective tool for the clinical documentation process.

[Endorsement of risk management and patient safety by certification of conformity in health care quality assessment]. / Unterstützende Wirkungen von Zertifizierungen auf das Risikomanagement und die Patientensicherheit in der Medizin.

Certification of conformity in health care should provide assurance of compliance with quality standards. This also includes risk management and patient safety. Based on a comprehensive definition of quality, beneficial effects on the management of risks and the enhancement of patient safety can be expected from certification of conformity. While these effects have strong face validity, they are currently not sufficiently supported by evidence from health care research. Whether this relates to a lack of evidence or a lack of investigation remains open. Advancing safety culture and "climate", as well as learning from adverse events rely in part on quality management and are at least in part reflected in the certification of healthcare quality. However, again, evidence of the effectiveness of such measures is limited. Moreover, additional factors related to personality, attitude and proactive action of healthcare professionals are crucial factors in advancing risk management and patient safety which are currently not adequately reflected in certification of conformity programs.

Assessment of nonischemic fibrosis in hypertrophic cardiomyopathy: comparison of gadopentetate dimeglumine and gadobenate dimeglumine for enhanced cardiovascular magnetic resonance imaging.

PURPOSE: To compare whether the higher relaxivity contrast agent gadobenate is superior for the identification of nonischemic late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) compared to standard relaxivity agents such as gadopentetate. MATERIALS AND METHODS: Fifteen patients with HCM and positive LGE based on routine cardiac magnetic resonance (CMR) with 0.2 mmol/kg gadopentetate were enrolled. Each patient thereafter underwent a second enhanced CMR exam with 0.2 mmol/kg gadobenate using the same CMR protocol. LGE was assessed in a short axis stack acquired after contrast administration using an inversion recovery gradient echo sequence. Two independent blinded readers quantified LGE by manual planimetry. The signal intensities of injured myocardium, remote myocardium, left ventricular cavity, and air were measured in identical locations using anatomical landmarks and dedicated software. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. RESULTS: No adverse events related to contrast administration occurred. Gadobenate dimeglumine showed a higher SNR of injured myocardium (45.4 ± 24.0 vs. 31.1 ± 16.6, P = 0.002) and a higher CNR between remote and injured myocardium (37.6 ± 25.0 vs. 26.5 ± 17.6, P = 0.006) compared to gadopentetate dimeglumine. The amount of LGE (based on the same postprocessing criteria and definitions) was higher with gadobenate dimeglumine (12.7 ± 8.5 g vs. 9.4 ± 5.6 g, P = 0.005). There was no difference in intra- and interobserver variability between gadopentetate dimeglumine and gadobenate dimeglumine. CONCLUSION: CMR with the high relaxivity contrast agent gadobenate dimeglumine reveals significantly more tissue with LGE in patients with HCM.

Variability and homogeneity of cardiovascular magnetic resonance myocardial T2-mapping in volunteers compared to patients with edema.

BACKGROUND: The aim of the study was to test the reproducibility and variability of myocardial T2 mapping in relation to sequence type and spatial orientation in a large group of healthy volunteers. For control T2 mapping was also applied in patients with true edema. Cardiovascular magnetic resonance (CMR) T2-mapping has potential for the detection and quantification of myocardial edema. Clinical experience is limited so far. The variability and potential pitfalls in broad application are unknown. METHODS: Healthy volunteers (n = 73, 35 ± 13 years) and patients with edema (n = 28, 55 ± 17 years) underwent CMR at 1.5 T. Steady state free precession (SSFP) cine loops and T2-weighted spin echo images were obtained. In patients, additionally late gadolinium enhancement images were acquired. We obtained T2 maps in midventricular short axis (SAX) and four-chamber view (4CV) based on images with T2 preparation times of 0, 24, 55 ms and compared fast low angle shot (FLASH) and SSFP readout. 10 volunteers were scanned twice on separate days. Two observers analysed segmental and global T2 per slice. RESULTS: In volunteers global myocardial T2 systematically differed depending on image orientation and sequence (FLASH 52 ± 5 vs. SSFP 55 ± 5 ms in SAX and 57 ± 6 vs. 59 ± 6 ms in 4CV; p < 0.0001 for both). Anteroseptal and apical segments had higher T2 than inferior and basal segments (SAX: 59 ± 6 vs. 48 ± 5 ms for FLASH and 59 ± 7 vs. 52 ± 4 ms for SSFP; p < 0.0001 for both). 14 volunteers had segments with T2 ≥ 70 ms. Mean intraobserver variability was 1.07 ± 1.03 ms (r = 0.94); interobserver variability was 1.6 ± 1.5 ms (r = 0.87). The coefficient of variation for repeated scans was 7.6% for SAX and 6.6% for 4CV. Mapping revealed focally increased T2 (73 ± 9 vs. 51 ± 3 ms in remote myocardium; p < 0.0001) in all patients with edema. CONCLUSIONS: Myocardial T2 mapping is technically feasible and highly reproducible. It can detect focal edema and differentiate it from normal myocardium. Increased T2 was found in some volunteers most likely due to partial volume and residual motion.

Myocardial T1 and T2 mapping at 3 T: reference values, influencing factors and implications.

BACKGROUND: Myocardial T1 and T2 mapping using cardiovascular magnetic resonance (CMR) are promising to improve tissue characterization and early disease detection. This study aimed at analyzing the feasibility of T1 and T2 mapping at 3 T and providing reference values. METHODS: Sixty healthy volunteers (30 males/females, each 20 from 20-39 years, 40-59 years, 60-80 years) underwent left-ventricular T1 and T2 mapping in 3 short-axis slices at 3 T. For T2 mapping, 3 single-shot steady-state free precession (SSFP) images with different T2 preparation times were acquired. For T1 mapping, modified Look-Locker inversion recovery technique with 11 single shot SSFP images was used before and after injection of gadolinium contrast. T1 and T2 relaxation times were quantified for each slice and each myocardial segment. RESULTS: Mean T2 and T1 (pre-/post-contrast) times were: 44.1 ms/1157.1 ms/427.3 ms (base), 45.1 ms/1158.7 ms/411.2 ms (middle), 46.9 ms/1180.6 ms/399.7 ms (apex). T2 and pre-contrast T1 increased from base to apex, post-contrast T1 decreased. Relevant inter-subject variability was apparent (scatter factor 1.08/1.05/1.11 for T2/pre-contrast T1/post-contrast T1). T2 and post-contrast T1 were influenced by heart rate (p < 0.0001, p = 0.0020), pre-contrast T1 by age (p < 0.0001). Inter- and intra-observer agreement of T2 (r = 0.95; r = 0.95) and T1 (r = 0.91; r = 0.93) were high. T2 maps: 97.7% of all segments were diagnostic and 2.3% were excluded (susceptibility artifact). T1 maps (pre-/post-contrast): 91.6%/93.9% were diagnostic, 8.4%/6.1% were excluded (predominantly susceptibility artifact 7.7%/3.2%). CONCLUSIONS: Myocardial T2 and T1 reference values for the specific CMR setting are provided. The diagnostic impact of the high inter-subject variability of T2 and T1 relaxation times requires further investigation.

HLA-DRB1*0401 and HLA-DRB1*0408 are strongly associated with the development of antibodies against interferon-beta therapy in multiple sclerosis.

The formation of antibodies to interferon-beta (IFN-beta), a protein-based disease-modifying agent for multiple sclerosis (MS), is a problem in clinical practice. These antibodies may neutralize the biological effects of the protein drug, potentially decreasing its therapeutic effects. By high-resolution HLA class I and II typing we identified two HLA class II alleles associated with the development of antibodies to IFN-beta. In two independent continuous and binary-trait association studies, HLA-DRB1*0401 and HLA-DRB1*0408 (odds ratio: 5.15)--but not other HLA alleles--were strongly associated with the development of binding and neutralizing antibodies to IFN-beta. The associated HLA-DRB1*04 alleles differ from nonassociated HLA-DRB1*04 alleles by a glycine-to-valine substitution in position 86 of the epitope-binding alpha-helix of the HLA class II molecule. The peptide-binding motif of HLA-DRB1*0401 and *0408 might promote binding and presentation of an immunogenic peptide, which may eventually break T cell tolerance and facilitate antibody development to IFN-beta. In summary, we identified genetic factors determining the immunogenicity of IFN-beta, a protein-based disease-modifying agent for the treatment of MS.

Prognostic impact of T2-weighted CMR imaging for cardiac amyloidosis.

OBJECTIVES: Using cardiac magnetic resonance imaging (MRI) we tested the diagnostic value of various markers for amyloid infiltration. METHODS: We performed MRI at 1.5 T in 36 consecutive patients with cardiac amyloidosis and 48 healthy volunteers. The protocol included cine imaging, T2-weighted spin echo, T1-weighted spin echo before and early after contrast and late gadolinium enhancement. We compared the frequency of abnormalities and their relation to mortality. RESULTS: Median follow-up was 31 months. Twenty-three patients died. Mean left ventricular (LV) mass was 205 ± 70 g. LV ejection fraction (EF) was 55 ± 12%. T2 ratio was 1.5 ± 0.4. 33/36 patients had pericardial and 22/36 had pleural effusions. All but two had heterogeneous late enhancement. Surviving patients did not differ from those who had died with regard to gender, LV mass or volume. Surviving patients had a significantly higher LVEF (60.4 ± 9.9% vs. 51.6 ± 11.5%; p = 0.03). The deceased patients had a lower T2 ratio than those who survived (1.38 ± 0.42 vs. 1.76 ± 0.17; p = 0.005). Low T2 was associated with shorter survival (Chi-squared 11.3; p < 0.001). Cox regression analysis confirmed T2 ratio < 1.5 as the only independent predictors for survival. CONCLUSION: Cardiac amyloidosis is associated with hypointense signal on T2-weighted images. A lower T2 ratio was independently associated with shortened survival.

Genetic variations of interleukin-23R (1143A>G) and BPI (A645G), but not of NOD2, are associated with acute graft-versus-host disease after allogeneic transplantation.

Single nucleotide polymorphisms (SNPs) in genes of the immune system predict for aGVHD and mortality after allo-SCT. We investigated the effect of SNPs in the NOD2, BPI, and IL-23R genes on posttransplantation outcome in a cohort of 304 patients. NOD2 patient and donor genotype and BPI recipient genotype were not associated with the occurrence of aGVHD. However, IL-23R-SNP in the donor was correlated with less aGVHD. This association could be confirmed in multivariate analysis (odds ratio [OR], 0.39; P = .039), which identified in vivo T cell depletion (OR, 0.32; P < .001) and multiagent GVHD prophylaxis (OR, 0.51; P = .031) as other independent factors predicting for less-severe aGVHD. This multivariate model also revealed a trend toward less aGVHD in patients receiving a BPI G allele transplant (OR, 0.60; P = .067) and in those receiving a transplant from an HLA-matched donor (OR, 0.57; P = .058). In contrast, relapse was more frequent in patients with NOD2-SNPs (46.2% for SNP vs 33.2% for wild-type; P = .020). This association was found to be of borderline significance in multivariate analysis. Neither BPI nor IL-23R genotype predicted for relapse, and none of the investigated SNPs was correlated with 5-year overall survival. In our analysis, NOD2 SNPs did not predict aGVHD, but IL-23R(1142A>G) and BPI(A645G) SNPs appeared to be promising markers in this regard. The importance of these markers in prediction models for GVHD and relapse remain to be defined in large prospective clinical trials.

Assessment of mitral bioprostheses using cardiovascular magnetic resonance.

BACKGROUND: The orifice area of mitral bioprostheses provides important information regarding their hemodynamic performance. It is usually calculated by transthoracic echocardiography (TTE), however, accurate and reproducible determination may be challenging. Cardiovascular magnetic resonance (CMR) has been proven as an accurate alternative for assessing aortic bioprostheses. However, whether CMR can be similarly applied for bioprostheses in the mitral position, particularly in the presence of frequently coincident arrhythmias, is unclear. The aim of the study is to test the feasibility of CMR to evaluate the orifice area of mitral bioprostheses. METHODS: CMR planimetry was performed in 18 consecutive patients with mitral bioprostheses (n = 13 Hancock(R), n = 4 Labcore(R), n = 1 Perimount(R); mean time since implantation 4.5 +/- 3.9 years) in an imaging plane perpendicular to the transprosthetic flow using steady-state free-precession cine imaging under breath-hold conditions on a 1.5T MR system. CMR results were compared with pressure half-time derived orifice areas obtained by TTE. RESULTS: Six subjects were in sinus rhythm, 11 in atrial fibrillation, and 1 exhibited frequent ventricular extrasystoles. CMR image quality was rated as good in 10, moderate in 6, and significantly impaired in 2 subjects. In one prosthetic type (Perimount(R)), strong stent artifacts occurred. Orifice areas by CMR (mean 2.1 +/- 0.3 cm2) and TTE (mean 2.1 +/- 0.3 cm2) correlated significantly (r = 0.94; p < 0.001). Bland-Altman analysis showed a 95% confidence interval from -0.16 to 0.28 cm2 (mean difference 0.06 +/- 0.11 cm2; range -0.1 to 0.3 cm2). Intra- and inter-observer variabilities of CMR planimetry were 4.5 +/- 2.9% and 7.9 +/- 5.2%. CONCLUSIONS: The assessment of mitral bioprostheses using CMR is feasible even in those with arrhythmias, providing orifice areas with close agreement to echocardiography and low observer dependency. Larger samples with a greater variety of prosthetic types and more cases of prosthetic dysfunction are required to confirm these preliminary results.

Aortic dilatation in patients with prosthetic aortic valve: comparison of MRI and echocardiography.

BACKGROUND AND AIM OF THE STUDY: Patients with prosthetic aortic valve have an increased risk for aortic dissection, which rises further with growing aortic diameters. Thus, accurate aortic monitoring is required. As transthoracic echocardiography (TTE), the current clinical standard, is frequently restricted to the proximal ascending aorta, the use of two-dimensional cardiovascular magnetic resonance (2D-CMR) in transverse orientation was investigated as a screening tool to assess ascending aortic dimensions. METHODS: Fast, non-contrast-enhanced, non-breath-hold, steady-state free-precession (SSFP) sequences (1.5 Tesla, slice thickness 7 mm, gap 1.8 mm, scan time 10-15 s) were applied to image the thorax in transverse planes. To test the accuracy of aortic dimensions obtained in this way, comparison was made to contrast-enhanced three-dimensional MR angiography (3D-MRA) as the 'gold standard' in 30 patients with aortic or aortic valve disease. After validation, transverse 2D-CMR was used to assess ascending aortic dimensions in 65 patients with aortic bioprostheses, and the results were compared to those acquired with TTE. RESULTS: Data acquired with both 2D-CMR and 3D-MRA agreed well when assessing ascending aortic diameters (r = 0.99; p < 0.001; mean difference 0.1 +/- 0.1 cm). In patients with bioprostheses, the image quality was diagnostic in 100% of cases for 2D-CMR, and in 93.4% for TTE. The ascending aortic diameter by 2D-CMR (mean 3.8 +/- 0.5 cm; range: 2.6-5.0 cm) was larger (p < 0.001) than by TTE (3.3 +/- 0.6 cm; range: 2.3-4.9 cm). Aortic dilatation (diameter, indexed by body surface area, > 2.1 cm/m2) was present in 38.5% of 2D-CMR cases and in 11.5% of TTE cases. The intra- and inter-observer variabilities to assess aortic dimensions by 2D-CMR were 2.1 +/- 1.9% and 4.3 +/- 3.7%, respectively. CONCLUSION: Imaging of the complete thorax in transverse orientation using fast, non-contrast-enhanced SSFP images provided an accurate and reliable approach to screen for aortic dilatation. In patients with aortic bioprostheses, 2D-CMR revealed a high prevalence of aortic dilatation, which was considerably underestimated by TTE.

An open-source software tool for the generation of relaxation time maps in magnetic resonance imaging.

BACKGROUND: In magnetic resonance (MR) imaging, T1, T2 and T2* relaxation times represent characteristic tissue properties that can be quantified with the help of specific imaging strategies. While there are basic software tools for specific pulse sequences, until now there is no universal software program available to automate pixel-wise mapping of relaxation times from various types of images or MR systems. Such a software program would allow researchers to test and compare new imaging strategies and thus would significantly facilitate research in the area of quantitative tissue characterization. RESULTS: After defining requirements for a universal MR mapping tool, a software program named MRmap was created using a high-level graphics language. Additional features include a manual registration tool for source images with motion artifacts and a tabular DICOM viewer to examine pulse sequence parameters. MRmap was successfully tested on three different computer platforms with image data from three different MR system manufacturers and five different sorts of pulse sequences: multi-image inversion recovery T1; Look-Locker/TOMROP T1; modified Look-Locker (MOLLI) T1; single-echo T2/T2*; and multi-echo T2/T2*. Computing times varied between 2 and 113 seconds. Estimates of relaxation times compared favorably to those obtained from non-automated curve fitting. Completed maps were exported in DICOM format and could be read in standard software packages used for analysis of clinical and research MR data. CONCLUSIONS: MRmap is a flexible cross-platform research tool that enables accurate mapping of relaxation times from various pulse sequences. The software allows researchers to optimize quantitative MR strategies in a manufacturer-independent fashion. The program and its source code were made available as open-source software on the internet.

Effects of sire line, birth weight and sex on growth performance and carcass traits of crossbred pigs under standardized environmental conditions.

A variety of available terminal sire lines makes the choice of terminal sire line complex for the pig producer. Higher birth weights are important for subsequent growth performance and selection for this trait is also necessary in sire lines. The aim was to investigate the effect of sire line, birth weight and gender on growth performance, carcass traits and meat quality. In total 3844 crossbred pigs from Camborough Pig Improvement Company (PIC) dams matched with either a Synthetic (A) or Piétrain (B) sire line were used. Pigs from line A grew faster ( p < 0.01 ), showed higher feed intake ( p < 0.01 ) and reached a higher final body weight ( p ≤ 0.01 ), but they had a similar efficiency ( p = 0.179 ). Leaner carcasses and heavier primal cuts ( p < 0.001 ) were observed in pigs from line B. Carcasses from pigs sired by line A had higher meat quality ( p < 0.001 ). Males had a higher growth rate ( p ≤ 0.05 ) but had a poorer feed efficiency ( p < 0.01 ). Heavier birth weight pigs and females had leaner, higher value carcasses with heavier primal cuts ( p < 0.001 ) compared to middle and low birth weight females or males. Sire line by sex interactions was significant for growth ( p ≤ 0.05 ) and carcass traits ( p < 0.001 ). Interaction between sire line and birth weight classes were only detected for loin depth ( p < 0.01 ). Line A is preferable if the numbers of fatting pigs per fattening place and year should be improved, and line B is an option to increase leanness and carcass primal cuts.

Cardiac magnetic resonance in acute myocarditis and dilated cardiomyopathy.

Cardiac magnetic resonance imaging can visualize ventricular size and function and moreover tissue composition. This allows for detection of myocardial edema and increased contrast uptake typical for inflammation. In a subset of myocarditis-patients typical irreversible fibrotic lesions can be detected. In clinical routine CMR can contribute to the differentiation of acute myocarditis and acute infarction or stress-induced cardiomyopathy. In various systemic diseases CMR can help to detect myocardial involvement. In dilated cardiomyopathy CMR enables precise quantification of ventricular size and function. The detection of myocardial fibrosis by CMR has prognostic implications.

Altered phenotype of natural killer cell subsets after haploidentical stem cell transplantation.

OBJECTIVE: Haplotype-mismatched CD34(+) selected allogeneic stem cell transplantation (HASCT) has been described as a therapeutic option for patients with acute myeloid leukemia. The success of this regimen is based mainly on natural killer (NK) cell-mediated antileukemia effects. MATERIALS AND METHODS: We prospectively investigated NK-cell (CD56(+)/CD3(-)) reconstitution, including expression of antileukemia effector molecules in patients undergoing HASCT. RESULTS: Although absolute NK-cell numbers rapidly increased, their phenotype notably differed compared to healthy controls. In fact, the "effector" CD56(dim) subset was significantly reduced, as was the NKG2D expression on "regulatory" CD56(bright) cells. Perforin was completely absent on NK cells in one-third of patients. The expression of Fas-ligand (Fas-L) on NK cells as well as soluble Fas-L and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plasma levels were also significantly lower after HASCT. In contrast, expression of TRAIL on CD56(dim) cells and interleukin-15 plasma levels were upregulated. Because the death rate due to relapse or infectious complications was high in the initial phase of the trial, subsequent patients received an adoptive infusion of donor NK cells followed by interleukin-2 in vivo in order to augment NK-cell function. This led to a distinct upregulation of perforin and Fas-L on the CD56(dim) subset accompanied by increased NK-cell cytotoxicity in vitro. CONCLUSION: The phenotype of reconstituting NK cells after HASCT is significantly altered. Whether the clinical outcomes of patients undergoing this regimen can be improved by a cytokine-based modulation of NK-cell activity needs to be determined.

Cardiovascular magnetic resonance imaging detects cardiac involvement in Churg-Strauss syndrome.

BACKGROUND: Cardiac involvement in Churg-Strauss vasculitis worsens the prognosis. Early detection is, therefore, warranted. Cardiac magnetic resonance (CMR) can visualize various forms of inflammatory changes in the myocardium. We tested whether CMR could elucidate cardiac damage in patients with biopsy-proven Churg-Strauss syndrome and clinical evidence of cardiac involvement. METHODS AND RESULTS: Eleven patients underwent a CMR protocol including cine imaging for left ventricular function in long axes, T2-weighted imaging for edema detection, and contrast-enhanced T1-weighting for early and late gadolinium enhancement. CMR detected various form of myocardial injury in all patients. Systolic left ventricular function was impaired in 6 patients. Mean left ventricular ejection fraction was 45 +/- 15%. Left ventricular size was mildly enlarged (left ventricular end-diastolic volume index 94 +/- 23 mL/m(2)). Edema was present in 4 cases; 7 patients had pericardial effusion. Six patients had increased early contrast uptake. CMR detected late enhancement lesions in 9 of 11 patients, even in those with normal left ventricular size and function. CONCLUSIONS: CMR has the potential to detect myocardial injury in Churg-Strauss syndrome even when left ventricular function appears normal.

Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis--a CMR study.

BACKGROUND: Myocardial edema is a substantial feature of the inflammatory response in human myocarditis. The relation between myocardial edema and myocardial mass in the course of healing myocarditis has not been systematically investigated. We hypothesised that the resolution of myocardial edema as visualised by T2-weighted cardiovascular magnetic resonance (CMR) is associated with a decrease of myocardial mass in steady state free precession (SSFP)-cine imaging. METHODS: 21 patients with acute myocarditis underwent CMR shortly after onset of symptoms and 1 year later. For visualization of edema, a T2-weighted breath-hold black-blood triple-inversion fast spin echo technique was applied and the ratio of signal intensity of myocardium/skeletal muscle was assessed. Left ventricular (LV) mass, volumes and function were quantified from biplane cine steady state free precession images. 11 healthy volunteers served as a control group for interstudy reproducibility of LV mass. RESULTS: In patients with myocarditis, a significant decrease in LV mass was observed during follow-up compared to the acute phase (156.7 +/- 30.6 g vs. 140.3 +/- 28.3 g, p < 0.0001). The reduction of LV mass paralleled the normalization of initially increased myocardial signal intensity on T2-weighted images (2.4 +/- 0.4 vs. 1.68 +/- 0.3, p < 0.0001). In controls, the interstudy difference of LV mass was lower than in patients (5.1 +/- 2.9 g vs. 16.3 +/- 14.2 g, p = 0.02) resulting in a lower coefficient of variability (2.1 vs 8.9%, p = 0.04). CONCLUSION: Reversible abnormalities in T2-weighted CMR are paralleled by a transient increase in left ventricular mass during the course of myocarditis. Myocardial edema may be a common pathway explaining these findings.

Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches.

OBJECTIVES: The aim of this research was to identify the diagnostic performance of gadolinium-enhanced and T2-weighted cardiovascular magnetic resonance (CMR) in suspected acute myocarditis. BACKGROUND: Acute myocarditis is difficult to diagnose; CMR provides various means to visualize myocardial inflammatory changes. A CMR approach with clear-cut diagnostic criteria would be desirable. METHODS: We investigated 25 patients with suspected acute myocarditis (18 males, 44 +/- 17 years) and 23 healthy controls (13 males, 29 +/- 10 years). Cardiovascular magnetic resonance studies included the following sequences: 1) T2-weighted triple inversion recovery; 2) T1-weighted spin echo before and over 4 min after gadolinium injection; and 3) inversion recovery-gradient echo 10 min after gadolinium injection. Qualitative and quantitative image analysis was performed for: 1) focal and global T2 signal intensity (SI); 2) myocardial global relative enhancement (gRE); and 3) areas of late gadolinium enhancement (LGE). RESULTS: Both global T2 SI and gRE were higher in patients than in controls (T2: 2.3 +/- 0.4 vs. 1.7 +/- 0.4; p < 0.0001, gRE: 6.8 +/- 4.0 vs. 3.7 +/- 2.3; p < 0.001). The sensitivity, specificity, and diagnostic accuracy for T2 (cutoff value of 1.9) were 84%, 74%, and 79%, respectively; gRE: (cutoff value of 4.0) 80%, 68%, and 74.5% respectively; LGE: 44%, 100%, and 71%, respectively. The best diagnostic performance was obtained when "any-two" of the three sequences were positive in the same patient yielding a 76% sensitivity, 95.5% specificity, and 85% diagnostic accuracy. CONCLUSIONS: A combined CMR approach using T2-weighted imaging, early and late gadolinium enhancement, provides a high diagnostic accuracy and is a useful tool in the diagnosis and assessment of patients with suspected acute myocarditis.

The Karlsburg type 1 diabetes risk study of a normal schoolchild population: association of beta-cell autoantibodies and human leukocyte antigen-DQB1 alleles in antibody-positive individuals.

The intent of this study was to analyze the prevalence of diabetes-associated autoantibodies (AAbs) at or above the 99(th) percentile as well as their association with human leukocyte antigen (HLA)-DQB1 alleles in a normal population of 6,337 schoolchildren. AAbs against glutamic acid decarboxylase (GADA), tyrosine phosphatase IA-2 (IA-2A), and/or insulin (IAA) were detected by (125)I-antigen binding and islet cell antibodies (ICA) immunohistochemically in 181 (2.86%) schoolchildren. HLA-DQB1 alleles were analyzed in 178/181 children and subsequently compared with 119 controls. 2.37% (150/6,337) possessed only one AAb, whereas 0.49% (31/6,337) had multiple AAbs but at increased levels (P < 0.001). Subjects with GADA, IA-2A, or IAA revealed an increased frequency of the diabetes-associated HLA-DQB1 alleles *0302 and/or *02 (P = 0.001-0.006) as well as a decreased frequency in the protective allele *0602 (P < 0.001-0.022). DQB1*0602 was completely absent within children with multiple AAbs or with GADA, IA2-A, or IAA at or above the 99.9(th) percentile. In comparison to children with single AAbs, the frequency of associated/protective alleles of children with multiple AAbs was enhanced/diminished (P = 0.004-0.009). The study shows that also in the general population the multiple AAbs or high level single AAbs predict rather certainly a HLA-DQB1-mediated diabetes susceptibility as shown for first degree relatives of type 1 diabetic patients.