MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

The gut microbiome in dogs with congestive heart failure: a pilot study

Compromised gut health and dysbiosis in people with heart failure has received a great deal of attention over the last decade. Whether dogs with heart failure have a similar dysbiosis pattern to what is described in people is currently unknown. We hypothesised that dogs with congestive heart failure have quantifiable dysbiosis compared to healthy dogs that are similar in sex and age. A total of 50 dogs (15 healthy dogs and 35 dogs with congestive heart failure) were prospectively recruited, and their faecal gut microbiome was assessed using 16S rRNA sequencing (Illumina MiSeq platform). There was no significant change in the microbial diversity and richness in dogs with congestive heart failure. However, there was an increase in abundance of Proteobacteria in the congestive heart failure group (p = 0.014), particularly due to an increase in the family Enterobacteriaceae (p = 0.002) and Escherichia coli (p = 0.033). We conclude that dogs with congestive heart failure have dysbiosis, and we show additional trends in our data suggesting that dogs may have a similar pattern to that described in people. The results of this study provide useful preliminary information and raise the possibility that dogs represent a clinically relevant animal model of dysbiosis in people with heart failure

Innate immunity and remodelling

A wide variety of cardiac disease states can induce remodelling and lead to the functional consequence of heart failure. These complex disease states involve a plethora of parallel signal transduction events, which may be associated with tissue injury or tissue repair. Innate immunity is activated in hearts injured in different ways, evident as cytokine release from the heart, activation of toll-like receptors involved in recognizing danger, and activation of the transcription factor nuclear factor kappa B. Nuclear factor kappa B regulates gene programmes involved in inflammation as well as the resolution of inflammation. The impact of this is an enigma; while cytokines, toll-like receptors, and nuclear factor kappa B appear to elicit myocardial protection in studies of preconditioning, the literature strongly indicates a detrimental role for activation of innate immunity in studies of acute ischaemia–reperfusion injury. The impact of activation of cardiac innate immunity on the long-term outcome in in vivo models of hypertrophy and remodelling is less clear, with conflicting results as to whether it is beneficial or detrimental. More research using genetically engineered mice as tools, different models of evoking remodelling, and long-term follow-up is required for us to conclude whether activation of the innate immune system is good, bad, or unimportant in chronic injury models

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and Epithelial Barrier Disruption

Aims: To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator

Longitudinal association between N-terminal B-type natriuretic peptide, anxiety and social support in patients with HFpEF: results from the multicentre randomized controlled Aldo-DHF trial

Background Higher plasma levels of natriuretic peptides (NPs) have been associated with reduced anxiety in experimental research and a number of patient samples. As NP levels are elevated in heart failure patients, we investigate whether this elevation is related to anxiety in patients with heart failure with preserved ejection fraction (HFpEF). Methods Post-hoc regression and mediation analyses were conducted, using data of 422 patients with HFpEF from the randomized, placebo-controlled, double-blinded, two-armed, multicentre aldosterone in diastolic heart failure trial, testing associations and their mediators between the N-terminal B-type natriuretic peptide (NT-proBNP) and anxiety at baseline and over 12-month follow-up. Anxiety was measured by the Hospital Anxiety and Depression Scale (HADS), social support by the ENRICHD Social Support Inventory and physical functioning by the Short Form 36 Health Survey. Results The mean age of the study population was 66.8 ± 7.6 years, 47.6% were male and 86.0% had NYHA class II. NT-proBNP showed a weak negative correlation with HADS anxiety scores at baseline (r = − 0.087; p = 0.092), which was significant (r = − 0.165; p = 0.028) in men but not in women. NT-proBNP also tended to predict lower anxiety at 12-months in men. On the other hand, higher anxiety at baseline was associated with lower NT-proBNP scores 12 months later (r = − 0.116; p = 0.026). All associations lost significance in multivariate regression for age, perceived social support (ESSI), physical function (SF-36) and study arm. Mediation analyses revealed that social support acts as a full mediator for the link between NT-proBNP levels and anxiety. Conclusion The mechanisms linking NT-proBNP to anxiety may be more complex than originally assumed. While effects of NT-proBNP on anxiety may be mediated by perceived social support, there may be an additional negative effect of anxiety on NT-proBNP. Future research should consider this possible bi-directionality of the association and assess the potential influence of gender, social support, oxytocin and vagal tone on the interaction of anxiety and natriuretic peptide levels. Trial Registration http://www.controlled-trials.com  (ISRCTN94726526) on 07/11/2006. Eudra-CT-number: 2006–002,605-31.Open-Access-Publikationsfonds 202

Segment-by-segment assessment of left ventricular myocardial affection in Anderson-Fabry disease by non-enhanced T1-mapping

Background: Anderson-Fabry disease (AFD) is an X-linked lysosomal enzyme disorder associated with an intracellular accumulation of sphingolipids, which shorten myocardial T1 relaxation times. Myocardial affection, however, varies between different segments. Purpose: To evaluate the specific segmental distribution and degree of segmental affection in AFD patients. Material and Methods: Twenty-five patients with AFD, 14 patients with hypertrophic cardiomyopathy (HCM), and 21 controls were included. A Modified Look-Locker Inversion Recovery sequence (MOLLI) was used for non-enhanced T1 mapping at 1.5 T in addition to standard cardiac imaging in 10-12 short axis views. T1 values were evaluated with a mixed model ANOVA and regression analysis to determine the best diagnostic cutoff values for T1 for each myocardial segment. Results: Regression analysis showed the best diagnostic cutoff compared to controls in cardiac segments 1-4, 8-9, and 14. Mean differences between T1 for AFD versus HCM were greatest in segment 3, 4, and 9 (99ms, 103ms, 86ms, respectively). Overall T1 times were 88870ms and 903 +/- 14ms (AFD with and without LVH); 1014 +/- 17ms and 1001 +/- 22ms (HCM and controls, P<0.05). Conclusion: Myocardial segments are affected by a varying degree of T1 shortening in AFD patients. Segment-specific cutoff values allow the most specific detection and quantification of the extent of myocardial affection

Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

AIMS: We aimed to assess determinants of anorexia, that is loss of appetite in patients with heart failure (HF) and aimed to further elucidate the association between anorexia, functional capacity, and outcomes in affected patients. METHODS AND RESULTS: We assessed anorexia status among 166 patients with HF (25 female, 66 ± 12 years) who participated in the Studies Investigating Co-morbidities Aggravating HF. Anorexia was assessed by a 6-point Likert scale (ranging from 0 to 5), wherein values ≥1 indicate anorexia. Functional capacity was assessed as peak oxygen uptake (peak VO2 ), 6 min walk test, and short physical performance battery test. A total of 57 patients (34%) reported any anorexia, and these patients showed lower values of peak VO2 , 6 min walk distance, and short physical performance battery score (all P < 0.05). Using multivariate analysis adjusting for clinically important factors, only high-sensitivity C-reactive protein [odds ratio (OR) 1.24, P = 0.04], use of loop diuretics (OR 5.76, P = 0.03), and the presence of cachexia (OR 2.53, P = 0.04) remained independent predictors of anorexia. A total of 22 patients (13%) died during a mean follow-up of 22.5 ± 5.1 months. Kaplan-Meier curves for cumulative survival showed that those patients with anorexia presented higher mortality (Log-rank test P = 0.03). CONCLUSIONS: Inflammation, use of loop diuretics, and cachexia are associated with an increased likelihood of anorexia in patients with HF, and patients with anorexia showed impaired functional capacity and poor outcomes.Open-Access-Publikationsfonds 2017peerReviewe

Sarcopenia and Endothelial Function in Patients With Chronic Heart Failure: Results From the Studies Investigating Comorbidities Aggravating Heart Failure (SICA-HF)

Objectives: Skeletal muscle wasting, also known as sarcopenia, has recently been identified as a serious comorbidity in patients with heart failure (HF). We aimed to assess the impact of sarcopenia on endothelial dysfunction in patients with HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Design: Cross-sectional study. Setting: Ambulatory patients with HF were recruited at Charite Medical School, Campus Virchow-Klinikum, Berlin, Germany. Participants: We assessed peripheral blood flow (arm and leg) in 228 patients with HF and 32 controls who participated in the Studies Investigating Comorbidities Aggravating HF (SICA-HF). Measurements: The appendicular skeletal muscle mass of the arms and the legs combined was assessed by dual energy x-ray absorptiometry (DEXA). Sarcopenia was defined as the appendicular muscle mass two standard deviations below the mean of a healthy reference group of adults aged 18 to 40 years, as suggested for the diagnosis of muscle wasting in healthy aging. All patients underwent a 6-minute walk test and spiroergometry testing. Forearm and leg blood flow were measured by venous occlusion plethysmography. Peak blood flow was assessed after a period of ischemia in the limbs to test endothelial function. Results: Sarcopenia was identified in 37 patients (19.5%). Patients with sarcopenia presented with lower baseline forearm blood flow (2.30 +/- 1.21 vs. 3.06 +/- 1.49 vs. 4.00 +/- 1.66 mL min(-1) 100 mL(-1); P = .02) than those without sarcopenia or controls. The group of patients with sarcopenia showed similar baseline leg blood flow (2.06 +/- 1.62 vs. 2.39 +/- 1.39 mL min(-1) 100 mL(-1); P = .11) to those without but lower values when compared to controls (2.06 +/- 1.62 vs. 2.99 +/- 1.28 mL min(-1) 100 mL(-1); P = .03). In addition, patients with and without sarcopenia presented with lower peak flow in the forearm when compared to controls (18.37 +/- 7.07 vs. 22.19 +/- 8.64 vs. 33.63 +/- 8.57 mL min(-1) 100 mL(-1); P < .001). A similar result was observed in the leg (10.89 +/- 5.61 vs. 14.66 +/- 7.19 vs. 21.37 +/- 13.16 mL min(-1) 100 mL(-1); P < .001). Peak flow in the forearm showed a significant correlation with exercise capacity (relative peak VO2: R = 0.47; P < .001; absolute peak VO2: R = 0.35; P < .001; and 6-min walk distance: R = 0.20; P < .01). Similar correlations were observed between peak flow in the leg and exercise capacity (absolute peak VO2: R = 0.42, P < .001; relative peak VO2: R = 0.41, P < .001; and 6-min walk test: R = 0.33; P < .001). Logistic regression showed peak flow in the leg to be independently associated with the 6-min walk distance adjusted for age, hemoglobin level, albumin, creatinine, presence of sarcopenia, and coronary artery disease (hazard ratio, 0.903; 95% confidence interval, 0.835-0.976; P = .01). Conclusion: Patients with HF associated with sarcopenia have impaired endothelial function. Lower vasodilatation had a negative impact on exercise capacity, particularly prevalent in patients with sarcopenia. (C) 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine