A severe influenza season in Austria and its impact on the paediatric population: mortality and hospital admission rates, november 2017 - march 2018.

BACKGROUND: In Austria paediatric influenza-associated hospitalisations and deaths have never been systematically monitored. We examined the influenza season 2017/18 in terms of hospitalisation and mortality in the Austrian paediatric population and put the results into perspective of the available data from the last 15 years. METHODS: Cases of influenza-associated hospitalisations and deaths for season 2017/18 in children below 18 years were retrospectively collected from 12 and 33 Austrian hospitals, respectively. Hospitalisation and mortality rates for the whole Austrian paediatric population were estimated, adjusting for the population in each catchment area. Two Austrian databases were queried for hospitalisations and deaths associated with influenza during 2002-2016. Rough estimate of the vaccination coverage was calculated from a survey on 100 inpatients. RESULTS: Influenza-related paediatric hospitalisation rate in season 2017/18 was estimated as 128 (CI: 122-135) per 100,000 children, much higher than the national average of 40 per 100,000 over the years 2002-2016. There were nine reported influenza-associated deaths among children, resulting in mortality rate of 0.67 (CI: 0.32-1.21) per 100,000 children. CONCLUSIONS: Reported influenza-associated hospitalisations and fatalities demonstrate a high burden of influenza in the Austrian paediatric population corresponding with very low vaccination coverage.

Inter-observer agreement and diagnostic accuracy of myocardial perfusion reserve quantification by cardiovascular magnetic resonance at 3 Tesla in comparison to quantitative coronary angiography.

BACKGROUND: Quantification of cardiovascular magnetic resonance (CMR) myocardial perfusion reserve (MPR) at 1.5 Tesla has been shown to correlate to invasive evaluation of coronary artery disease (CAD) and to yield good inter-observer agreement. However, little is known about quantitative adenosine-perfusion CMR at 3 Tesla and no data about inter-observer agreement is available. Aim of our study was to evaluate inter-observer agreement and to assess the diagnostic accuracy in comparison to quantitative coronary angiography (QCA). METHODS: Fifty-three patients referred for coronary x-ray angiography were previously examined in a 3 Tesla whole-body scanner. Adenosine and rest perfusion CMR were acquired for the quantification of MPR in all segments. Two blinded and independent readers analyzed all images. QCA was performed in case of coronary stenosis. QCA data was used to assess diagnostic accuracy of the MPR measurements. RESULTS: Inter-observer agreement was high for all myocardial perfusion territories (ρ = 0.92 for LAD, ρ = 0.93 for CX and RCA perfused segments). Compared to QCA receiver-operating characteristics yielded an area under the curve of 0.78 and 0.73 for RCA, 0.66 and 0.69 for LAD, and 0.52 and 0.53 for LCX perfused territories. CONCLUSIONS: Inter-observer agreement of MPR quantification at 3 Tesla CMR is very high for all myocardial segments. Diagnostic accuracy in comparison to QCA yields good values for the RCA and LAD perfused territories, but moderate values for the posterior LCX perfused myocardial segments.

Ivabradine reduces chemokine-induced CD4-positive lymphocyte migration.

AIMS: Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. METHODS AND RESULTS: Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0 ± 0.1 fold increase in cell migration (P < .01; n = 7). Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2 ± 0.1 fold induction at 0.1 µmol/L ivabradine (P < .01 compared to SDF-1-treated cells, n = 7). The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC). Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. CONCLUSION: Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect.

Vitamin C supplement use may protect against gallstones: an observational study on a randomly selected population.

BACKGROUND: Animal experiments have shown a protective effect of vitamin C on the formation of gallstones. Few data in humans suggest an association between reduced vitamin C intake and increased prevalence of gallstone disease. The aim of this study was to assess the possible association of regular vitamin C supplementation with gallstone prevalence. METHODS: An observational, population-based study of 2129 subjects aged 18-65 years randomly selected from the general population in southern Germany was conducted. Abdominal ultrasound examination, completion of a standardized questionnaire, compilation of anthropometric data and blood tests were used. Data were collected in November and December 2002. Data analysis was conducted between December 2005 and January 2006. RESULTS: Prevalence of gallstones in the study population was 7.8% (167/2129). Subjects reporting vitamin C supplementation showed a prevalence of 4.7% (11/232), whereas in subjects not reporting regular vitamin C supplementation, the prevalence was 8.2% (156/1897). Female gender, hereditary predisposition, increasing age and body-mass index (BMI) were associated with increased prevalence of gallstones. Logistic regression with backward elimination adjusted for these factors showed reduced gallstone prevalence for vitamin C supplementation (odds ratio, OR 0.34; 95% confidence interval, CI 0.14 to 0.81; P = 0.01), increased physical activity (OR 0.62; 95% CI, 0.42 to 0.94; P = 0.02), and higher total cholesterol (OR 0.65; 95% CI, 0.52 to 0.79; P < 0.001). CONCLUSION: Regular vitamin C supplementation and, to a lesser extent, increased physical activity and total cholesterol levels are associated with a reduced prevalence of gallstones. Regular vitamin C supplementation might exert a protective effect on the development of gallstones.

Pregnancy is not a risk factor for gallstone disease: results of a randomly selected population sample.

AIM: To investigate the prevalence, risk factors, and selection of the study population for cholecystolithiasis in an urban population in Germany, in relation to our own findings and to the results in the international literature. METHODS: A total of 2 147 persons (1,111 females, age 42.8+/-12.7 years; 1,036 males, age 42.3+/-13.1 years) participating in an investigation on the prevalence of Echinococcus multilocularis were studied for risk factors and prevalence of gallbladder stone disease. Risk factors were assessed by means of a standardized interview and calculation of body mass index (BMI). A diagnostic ultrasound examination of the gallbladder was performed. Data were analyzed by multiple logistic regression, using the SAS statistical software package. RESULTS: Gallbladder stones were detected in 171 study participants (8.0%, n=2,147). Risk factors for the development of gallbladder stone disease included age, sex, BMI, and positive family history. In a separate analysis of female study participants, pregnancy (yes/no) and number of pregnancies did not exert any influence. CONCLUSION: Findings of the present study confirm that age, female sex, BMI, and positive family history are risk factors for the development of gallbladder stone disease. Pregnancy and the number of pregnancies, however, could not be shown to be risk factors. There seem to be no differences in the respective prevalence for gallbladder stone disease in urban and rural populations.

Early diagnosis of cardiac involvement in idiopathic inflammatory myopathy by cardiac magnetic resonance tomography.

The aim of this study was to investigate cardiac involvement in patients with idiopathic inflammatory myopathies excluding inclusion body myositis with cardiac magnetic resonance tomography (CMR). A case series of 53 patients with polymyositis, dermatomyositis, or non-specific myositis underwent CMR including functional imaging, T1-weighted, and late gadolinium enhancement (LGE) imaging. T1-weighted and LGE images were analyzed for myocardial enhancement. Reduced left ventricular function (LVF) was found in 9 (7%) patients. Patients with reduced LVF more often presented with early and late myocardial enhancement (p = 0.014 and p = 0.001). In 33 (62.3%) patients, LGE was observed by CMR. These patients had significantly lower left ventricular ejection fractions (p < 0.001) compared to patients without LGE. LGE was mainly present in the lateral (p < 0.01) and inferior (p < 0.02) segments. No correlations of LGE presence or reduced LVF to cardiovascular risk factors were found. Myocardial inflammation is very frequent in polymyositis, dermatomyositis, and non-specific myositis. In our patient, cohort CMR demonstrated signs of myocardial inflammation in 62.3%. CMR seems to offer a measurable and quantifiable diagnostic tool for cardiac involvement of idiopathic inflammatory myopathies and can thus be used to monitor disease progress and therapeutic success in these patients.

Is contrast-enhanced cardiac magnetic resonance imaging at 3 T superior to 1.5 T for detection of coronary artery disease?

The aim is to compare a compiled clinical routine cardiac magnetic resonance (CMR) imaging protocol performed at both 1.5 and 3 T in patients with suspected coronary artery disease (CAD) undergoing coronary X-ray angiography. CMR including adenosine perfusion and late gadolinium enhancement (LGE) at 1.5 T has been established for noninvasive detection of relevant CAD. However, little is known about the potential advantages of 3 T to detect CAD. Fifty-two evaluable patients (62.3 ± 10.2 years) were included into the study. All patients were scanned at both 1.5 and 3 T including adenosine stress and rest perfusion, and LGE imaging. CMR images were analyzed by two blinded readers in consensus. X-Ray angiography served as the reference method. A significant CAD was diagnosed by quantitative coronary analysis. Diagnostic accuracy of the combined analysis of perfusion and LGE imaging yielded better values at 1.5 and 3 T than the analysis of perfusion images alone. Specificity and sensitivity at 3 T was superior to 1.5 T in detecting coronary stenoses ≥50 % (90 vs. 75 % and 84.4 vs. 75 %) and ≥70 % (88 vs. 80 % and 96.3 vs. 88.9 %). This study showed that CMR at 3 T in a routine clinical setting is superior to 1.5 T in detection of significant CAD. 3 T might become the preferred CMR field strength for evaluation of CAD in clinical practice.

Intermediate-term prognostic value of reversible perfusion deficit diagnosed by adenosine CMR: a prospective follow-up study in a consecutive patient population.

OBJECTIVES: The aim of this study was to assess the hypothesis that cardiac magnetic resonance (CMR) myocardial perfusion imaging can provide incremental prognostic value over other risk factors regarding the prediction of major cardiovascular events in a large, consecutive, and thereby unselected population of patients presenting with stable angina pectoris. BACKGROUND: Recently, it has been shown that CMR provides good short-term prognosis in patients with stable coronary heart disease. Reversible myocardial ischemia can be assessed using a combination of perfusion and late gadolinium enhancement imaging. Data concerning intermediate-term prognostic information, especially on major clinical endpoints such as cardiac death or myocardial infarction, are limited. METHODS: From 2003 to 2007, consecutive patients with stable angina pectoris who underwent adenosine perfusion CMR were enrolled unless they met the predefined exclusion criteria. Myocardial perfusion imaging by adenosine stress and late gadolinium enhancement was assessed using a 1.5-T whole-body CMR scanner. Follow-up information concerning the combined endpoint of cardiac death, nonfatal myocardial infarction, and stroke was obtained from patients, general practitioners, or treating hospitals, respectively. RESULTS: In our study, 1,229 consecutive patients were enrolled. The mean follow-up period was 4.2 ± 2.1 years. During this time, 88 primary endpoints occurred. In patients with reversible perfusion deficits, significantly more cardiac deaths (p < 0.0001) and nonfatal myocardial infarctions (p = 0.001) were observed than in the control group. On multivariate analysis, reversible perfusion deficit was the strongest independent predictor for an event, with a 3-fold increased risk. Moreover, the absence of a perfusion deficit was shown to exhibit high negative predictive value. CONCLUSIONS: Adenosine perfusion CMR provides excellent risk stratification and intermediate-term prognostic value in patients with stable coronary artery disease. The presence of a myocardial perfusion deficit is an incremental prognostic risk factor over other risk factors.

Angiographic validation of magnetic resonance assessment of myocardium at risk in non-ST-elevation myocardial infarction.

In the setting of acute myocardial ischemia, the hypoperfused portion of the myocardium is in danger of becoming irreversibly injured. This portion is called the area at risk (AAR). It is of clinical interest to be able to estimate the AAR for further evaluation and improvement of different revascularization strategies. The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) has been shown to be a jeopardy score with a good performance for angiographic assessment of the myocardium supplied by a coronary vessel, representing the AAR. Recently, cardiac magnetic resonance imaging (CMR) has been demonstrated to also provide good results in determining the AAR, especially in the setting of acute ST-elevation infarction patients. Therefore, the aim of our trial was to compare T2-weighted CMR imaging for assessment of AAR in patients with non-ST-elevation myocardial infarction (NSTEMI) and to validate this approach against the angiographic APPROACH-score. We enrolled sixty-four patients presenting with acute NSTEMI that underwent coronary X-ray angiography within 72 h of symptom onset. Two blinded readers performed offline angiographic AAR assessment using the modified APPROACH-score, as being described elsewhere. Furthermore, with the use of a semi-automatic T2w-CMR approach, the AAR was quantified by two fully blinded readers. The resulting mean AAR determined by the modified APPROACH-score was 28.6 ± 10.0 %. The mean CMR derived AAR was 27.6 ± 12.7 %. CMR assessment tended to slightly underestimate the AAR in comparison to angiographic scoring (difference -0.09 ± 7.6 %). There is a good correlation between the AAR assessed by CMR and by angiography (r = 0.65, p < 0.001). T2-weigthed CMR is able to quantify the AAR with very good correlation to the angiographic APPROACH-score in NSTEMI patients.

Quantification of myocardial perfusion reserve at 1.5 and 3.0 Tesla: a comparison to fractional flow reserve.

The objective of this study was to compare quantitative analysis of cardiac magnetic resonance (CMR) perfusion at 1.5 and 3 T against fractional flow reserve (FFR) as measured invasively. FFR is considered by many investigators to be a reliable standard to determine hemodynamically significant coronary artery stenoses. Quantitative 1.5 and 3 T CMR is capable to noninvasively determine myocardial perfusion reserve, but have not been compared against each other and validated against FFR as standard reference. Patients with suspected or known coronary artery disease (CAD) underwent CMR at at both field strengths, 1.5 and 3 T, and FFR. 34 patients were included into the study. Quantitative myocardial perfusion reserve was calculated in 544 myocardial segments at 1.5 and 3 T, respectively. FFR was measured in 109 coronary arteries. FFR ≤ 0.8 was regarded relevant. Reduced FFR (≤0.8) was found in 38 coronary arteries (19 LAD, 8 LCX and 11 RCA). Receiver operator curve analysis yielded higher area under the curve for 3 T CMR in comparison to 1.5 T CMR (0.963 vs. 0.645, p < 0.001) resulting in higher sensitivity (90.5 vs. 61.9 %) and specificity (100 vs. 76.9 %). Quantitative analysis of CMR myocardial perfusion reserve at 1.5 and 3 T is capable to detect hemodynamic significance of coronary artery stenoses. Diagnostic accuracy at 3 T is to be superior to 1.5 T.

Myocardial perfusion reserve assessed by T2-prepared steady-state free precession blood oxygen level-dependent magnetic resonance imaging in comparison to fractional flow reserve.

BACKGROUND: Blood oxygen level-dependent (BOLD) cardiac magnetic resonance imaging (CMR) has been shown to be able to detect myocardial perfusion differences. However, validation of BOLD CMR against fractional flow reserve (FFR) is lacking. The aim of our study was to analyze the potential diagnostic accuracy of BOLD CMR in comparison to invasively measured FFR, which served as gold standard for a hemodynamic significant coronary lesion. METHODS AND RESULTS: BOLD image was performed at rest and during adenosine infusion in a 1.5-T CMR scanner. Thirty-six patients were analyzed for relative BOLD signal intensity increase according to the 16-segment model. Invasive FFR measurements were performed in the 3 major coronary arteries during adenosine infusion in all patients. An FFR≤0.8 was regarded to indicate a significant coronary lesion. Relative BOLD signal intensity increase was significantly lower in myocardial segments supplied by coronary arteries with an FFR≤0.8 compared with segments with an FFR>0.8 (1.1±0.2 versus 1.5±0.2; P<0.0001). Sensitivity and specificity yielded 88.2% and 89.5%, respectively. CONCLUSIONS: CMR BOLD imaging reliably detects hemodynamic significant coronary artery disease and is, thus, an alternative to contrast-enhanced perfusion studies.

Detection of long-term progression of myocardial fibrosis in Duchenne muscular dystrophy in an affected family: a cardiovascular magnetic resonance study.

BACKGROUND: Detection of myocardial fibrosis and left ventricular dysfunction in Duchenne muscular dystrophy (DMD) is the corner stone for further therapeutic studies. Little is known about the ability of cardiac magnetic resonance imaging (CMR) to evaluate progression of myocardial fibrosis. Aim of our study was to provide CMR data in a previously genotyped DMD family and to evaluate whether progression of myocardial fibrosis could be visualized. METHODS AND RESULTS: DMD genotypes were available in 14 family members. CMR was performed in 4/5 carrier females, in 2/2 affected males and in one healthy family member with normal genotype. Functional images and late gadolinium enhanced (LGE) images in contiguous short-axis orientation were acquired at baseline and follow-up of 1231 days CMR examination could be repeated in three carrier females, in one affected male and in the healthy subject previously scanned. Mean decrease of left ventricular ejection fraction during the follow-up period was 10.5±11.0%, mean progression of LGE volume 11.7±9.5%. CONCLUSIONS: Myocardial fibrosis seems to occur prior to global left ventricular dysfunction in DMD diseased males and carrier females. CMR could be used to evaluate progression of myocardial fibrosis and left ventricular function and may thus serve as an important diagnostic tool in the evaluation of therapeutical options in DMD.

The effect of alcohol, tobacco and caffeine consumption and vegetarian diet on gallstone prevalence.

AIM: To investigate the effects of alcohol, tobacco and caffeine consumption and of vegetarian diet on gallstone prevalence in an urban population sample. METHODS: A total of 2417 individuals underwent ultrasound examination and completed a standardized questionnaire as part of the EMIL study. Statistical analysis of the data considered the known risk factors of age, female sex, BMI, positive family history and potential confounders, such as alcohol, caffeine and tobacco consumption and vegetarian diet using multiple logistic regression with variable selection. RESULTS: The prevalence of gallstones in the population sample was 8% (171 out of 2147). Findings of the study confirmed the classic risk factors of age, female sex, obesity and positive family history. After the variable selection of potential risk factors in a logistic regression that was adjusted for age, female sex, BMI and positive family history, the factors like tobacco [odds ratio (OR) 1.09, 95% confidence interval (CI): 0.76-1.56, P=0.64] and caffeine consumption (OR: 0.77, 95% CI: 0.42-1.42, P=0.40) as well as vegetarian diet (OR: 1.14, 95% CI: 0.39-3.35, P=0.81) had no effect on gallstone prevalence. A protective effect against development of gallstones was shown for alcohol consumption (OR: 0.67, 95% CI: 0.46-0.99, P=0.04). CONCLUSION: The factors like tobacco and caffeine consumption as well as vegetarian diet exerted no measurable effect on the prevalence of gallstones. A protective effect was found for alcohol consumption.

Cardiac involvement in a female carrier of Duchenne muscular dystrophy.

A 42 year-old female carrier of Duchenne muscular dystrophy (DMD) was referred with suspected subacute myocarditis and non-sustained ventricular tachycardia. Echochardiography and cardiac catheterization revealed severely reduced left ventricular function (LVF). Coronary artery disease was excluded. Cardiac magnetic resonance imaging showed transmural, intramural and subepicardial late gadolinium enhancement. Myocardial biopsy excluded viral infection and showed severe myopathic changes with abnormal expression of dystrophin and utrophin. Moleculargenetic analysis of the DMD gene revealed frameshift duplication of exon 2. The patient received conventional heart failure therapy, implantable cardioverter/defibrillator-implantation and prednisolone to attenuate cardiac degradation. 6 months later she had improved clinically though LVF was still severely reduced.

Rapid effect of single-dose rosiglitazone treatment on endothelial function in healthy men with normal glucose tolerance: data from a randomised, placebo-controlled, double-blind study.

Antidiabetic thiazolidinediones (TZDs) improve endothelial function in patients with or without type 2 diabetes. The present randomised, placebo-controlled, double-blind study examined the time course of a single dose of rosiglitazone on flow-mediated endothelium-dependent vasodilation (FMD), metabolic parameters, and its effect on inflammatory markers in non-diabetic men. Forty non-obese, healthy men with normal glucose tolerance were randomised to a single dose of rosiglitazone (8 mg) or placebo, and FMD was assessed at baseline as well as after 6 h and 24 h. Rosiglitazone did not significantly affect blood glucose and insulin levels or lipid parameters after 6 and 24 h compared with placebo. Treatment with rosiglitazone significantly increased FMD after 6 h from 4.3% (3.3; 4.9) to 7.6% (5.6; 9.2) (p<0.0001 vs. baseline) resulting in a highly significant effect compared with placebo (p<0.0001 for difference between groups). After 24 h FMD was still significantly higher in the rosiglitazone group compared with baseline (p=0.001), but the effect was no longer statistically significant versus placebo (p=0.171). Our study shows a very rapid effect of single dose rosiglitazone treatment on endothelial function in non-diabetic healthy men, underscoring the hypothesis that TZDs may exhibit direct effect in the vasculature independent of their metabolic action.