Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of iron load and relationship to left ventricular ejection fraction

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR‐derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P < 0·001). The prevalence of CD was 32·9% in patients with T2* ≤ 8 ms, 12·5% in patients with T2* > 8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14–20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible.     

Volumetric tomography of fluorescent proteins through small animals in vivo

Volumetric detection and accurate quantification of fluorescent proteins in entire animals would greatly enhance our ability to monitor biological processes in vivo. Here we present a quantitative tomographic technique for visualization of superficial and deep-seated (>2-3 mm) fluorescent protein activity in vivo. We demonstrate noninvasive imaging of lung tumor progression in a murine model, as well as imaging of gene delivery using a herpes virus vector. This technology can significantly improve imaging capacity over the current state of the art and should find wide in vivo imaging applications in drug discovery, immunology, and cancer research.     

Lipidomics in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder in Western countries, comprises steatosis to nonalcoholic steatohepatitis (NASH), with the latter having the potential to progress to cirrhosis. The transition from isolated steatosis to NASH is still poorly understood, but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression. Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD. Changes in glycerophospholipid, sphingolipid, and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD, implicating that specific lipid species are involved in oxidative stress, inflammation, and cell death. In this article, we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.     

Candida albicans colonization on an intragastric balloon

Here we present the case of Candida albicans colonization on an intragastric balloon placed for weight loss. A 52‐year‐old obese woman achieved a BMI reduction of 10.9 kg/m² within 7 months as a result of a BioEnterics Intragastric Balloon and a well‐balanced, low‐calorie diet. During endoscopy for balloon removal, the balloon, which was well impacted in the gastric fundus, was found to be lime green in color with clusters of cone‐shaped cultures on its surface. Microbiology assessment revealed the presence of Candida albicans, although the patient was totally asymptomatic.     

Slowing down as an early warning signal for abrupt climate change

In the Earth's history, periods of relatively stable climate have often been interrupted by sharp transitions to a contrasting state. One explanation for such events of abrupt change is that they happened when the earth system reached a critical tipping point. However, this remains hard to prove for events in the remote past, and it is even more difficult to predict if and when we might reach a tipping point for abrupt climate change in the future. Here, we analyze eight ancient abrupt climate shifts and show that they were all preceded by a characteristic slowing down of the fluctuations starting well before the actual shift. Such slowing down, measured as increased autocorrelation, can be mathematically shown to be a hallmark of tipping points. Therefore, our results imply independent empirical evidence for the idea that past abrupt shifts were associated with the passing of critical thresholds. Because the mechanism causing slowing down is fundamentally inherent to tipping points, it follows that our way to detect slowing down might be used as a universal early warning signal for upcoming catastrophic change. Because tipping points in ecosystems and other complex systems are notoriously hard to predict in other ways, this is a promising perspective.     

Postoperative Atrial Fibrillation or Flutter Following Transcatheter or Surgical Aortic Valve Replacement: PARTNER 3 Trial

ObjectivesThe aim of this study was to assess the incidence and prognostic impact of early and late postoperative atrial fibrillation or flutter (POAF) in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).BackgroundThere is an ongoing controversy regarding the incidence, recurrence rate, and prognostic impact of early (in-hospital) POAF and late (postdischarge) POAF in patients with AS undergoing TAVR or SAVR.MethodsIn the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial, patients with severe AS at low surgical risk were randomized to TAVR or SAVR. Analyses were performed in the as-treated population excluding patients with preexistent atrial fibrillation or flutter.ResultsAmong 781 patients included in the analysis, early POAF occurred in 152 (19.5%) (18 of 415 [4.3%] and 134 of 366 [36.6%] following TAVR and SAVR, respectively). Following discharge, 58 new or recurrent late POAF events occurred within 1 year following the index procedure in 55 of 781 patients (7.0%). Early POAF was not an independent predictor of late POAF following discharge (odds ratio: 1.04; 95% CI: 0.52-2.08; P = 0.90). Following adjustment, early POAF was not an independent predictor of the composite outcome of death, stroke, or rehospitalization (hazard ratio: 1.10; 95% CI: 0.64-1.92; P = 0.72), whereas late POAF was associated with an increased adjusted risk for the composite outcome (hazard ratio: 8.90; 95% CI: 5.02-15.74; P < 0.0001), irrespective of treatment modality.ConclusionsIn the PARTNER 3 trial, early POAF was more frequent following SAVR compared with TAVR. Late POAF, but not early POAF, was significantly associated with worse outcomes at 2 years, irrespective of treatment modality.     

Optoacoustic detection of tissue glycation

Oxidative-based diseases including diabetes, chronic renal failure, cardiovascular diseases and neurological disorders are accompanied by accumulation of advanced glycation endproducts (AGE). Therefore, AGE-associated changes in tissue optical properties could yield a viable pathological indicator for disease diagnostics and monitoring. We investigated whether skin glycation could be detected based on absorption changes associated with AGE accumulation using spectral optoacoustic measurements and interrogated the optimal spectral band for skin glycation determination. Glycated and non-glycated skin was optoacoustically measured at multiple wavelengths in the visible region. The detected signals were spectrally processed and compared to measurements of skin auto-fluorescence and to second harmonic generation multiphoton microscopy images. Optoacoustic measurements are shown to be capable of detecting skin glycolysis based on AGE detection. A linear dependence was observed between optoacoustic intensity and the progression of skin glycation. The findings where corroborated by autofluorescence observations. Detection sensitivity is enhanced by observing normalised tissue spectra. This result points to a ratiometric method for skin glycation detection, specifically at 540 nm and 620 nm. We demonstrate that optoacoustic spectroscopy could be employed to detect AGE accumulation, and possibly can be employed as a non-invasive quick method for monitoring tissue glycation.OCIS codes: (110.5125) Photoacoustics, (170.5810) Scanning microscopy, (170.6510) Spectroscopy, tissue diagnostics, (180.4315) Nonlinear microscopy