Time to shape up – assessment and reporting standards for data quality in clinical research using echocardiographic imaging techniques require improvement

Abstract: Advanced echocardiography techniques such as speckle tracking imaging are sensitive diagnostic tools frequently used in various clinical and scientific scenarios. Importantly, imperfect reproducibility and dependence of post-processing algorithms on echocardiographic image quality are potential methodological limitations. Therefore, meticulous assessment of data quality and detailed reporting of study methodology, sample specifics, technical peculiarities and measurement conditions are crucial. Unfortunately, despite the recognized importance of this, there is still no broadly accepted standard for assessing the quality of echocardiographic images in clinical research reports. This article quintessentially highlights important shortcomings of data quality assessment and methodological study design, commonly occurring in clinical research reports using advanced echocardiography techniques. Finally, suggestions are made as to how researchers, scientific communities and biomedical journals can contribute to the ever-lasting process of improving the quality of clinical research in cardiovascular imaging

Novel functional advanced echocardiography for the assessment of myocardial mechanics in children with neurocardiogenic syncope - a blinded prospective speckle tracking head-up tilt-table challenge study.

BACKGROUND: Data on left ventricular (LV) function in patients with neurocardiogenic syncope (NS) is conflicting in adults and lacking in children. The aim of this study was to analyze LV myocardial performance in children with NS at rest and during head-up tilt-table (HUTT) testing. METHODS: This is the first study to combine HUTT and speckle-tracking echocardiography (STE) in children with NS. 43 consecutive normotensive pediatric patients with NS (mean age 13.9 ± 2.6 years, 51% female) and 41 sex- and age-matched healthy controls were included in the study. The study groups consisted of 21 patients with a positive HUTT reaction (HUTT+) and 22 with a negative HUTT reaction (HUTT-). STE was used to analyze peak systolic LV myocardial strain and strain rate. RESULTS: Conventional echocardiographic parameters were similar in all analyzed groups. When compared to healthy controls, children with NS had depressed levels of circumferential strain rate (p = 0.032) and significantly depressed longitudinal strain rate (p <  0.001) at rest. Interestingly, during HUTT testing LV global strain and strain rate were similar in both groups. LV strain rate was lowest in HUTT+ followed by HUTT- and control subjects both at rest and during HUTT. CONCLUSIONS: Resting LV longitudinal strain rate is attenuated in children with NS, especially in those with a positive HUTT response. This is further evidence that NS patients feature altered cardiac mechanics rendering them prone to vasovagal perturbations that can ultimately result in collapse. TRIAL REGISTRATION: Witten/Herdecke University ethics committee clinical study number: UWH-73-2014

Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.

BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. CONCLUSIONS: As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations

Guidance on the interpretation of faecal calprotectin levels in children.

BACKGROUND: Faecal calprotectin (FCP) is a powerful tool to predict inflammatory bowel disease (IBD) in patients with gastrointestinal symptoms. In the paediatric patient population, the reference value of 50 μg/g, 15% were ≥ 250 μg/g. Children 50 μg/g) was the sole reason for being referred for suspected IBD did not have IBD. CONCLUSION: Children with an FCP < 600 μg/g and without matching symptoms suggestive of IBD are unlikely to have IBD. A higher FCP reference value may provide cost-effective improvement that could avoid redundant investigations and specialist referrals. A guideline for specialist referrals is proposed

Sensitivity to Experiencing Alcohol Hangovers: Reconsideration of the 0.11% Blood Alcohol Concentration (BAC) Threshold for Having a Hangover

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their “normal” drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their “regular” drinking level, considerably higher alcohol intake—irrespective of the absolute amount—may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned

Time to shape up – assessment and reporting standards for data quality in clinical research using echocardiographic imaging techniques require improvement

Abstract: Advanced echocardiography techniques such as speckle tracking imaging are sensitive diagnostic tools frequently used in various clinical and scientific scenarios. Importantly, imperfect reproducibility and dependence of post-processing algorithms on echocardiographic image quality are potential methodological limitations. Therefore, meticulous assessment of data quality and detailed reporting of study methodology, sample specifics, technical peculiarities and measurement conditions are crucial. Unfortunately, despite the recognized importance of this, there is still no broadly accepted standard for assessing the quality of echocardiographic images in clinical research reports. This article quintessentially highlights important shortcomings of data quality assessment and methodological study design, commonly occurring in clinical research reports using advanced echocardiography techniques. Finally, suggestions are made as to how researchers, scientific communities and biomedical journals can contribute to the ever-lasting process of improving the quality of clinical research in cardiovascular imaging

Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.

BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. CONCLUSIONS: As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations

Speckle-Tracking and Tissue-Doppler Stress Echocardiography in Arterial Hypertension: A Sensitive Tool for Detection of Subclinical LV Impairment

Early diagnosis of cardiac alterations in hypertensive heart disease is still challenging. Since such patients might have depressed global LV systolic strain or strain rate when EF is still normal, speckle-tracking echocardiography (STE) and tissue-Doppler imaging (TDI) combined with stress echocardiography might improve early diagnosis of cardiac alterations. In this prospective study standard 2D Doppler echocardiography, STE, and TDI were performed at rest and during bicycle exercise in 92 consecutive patients—46 hypertensive subjects with normal ejection fraction and 46 healthy controls. STE and TDI were used to measure global peak systolic LV circumferential strain (CS), longitudinal strain (LS), and longitudinal strain rate (SR). Mean arterial blood pressure was significantly higher in hypertensive patients at rest (100.8 mmHg SD 13.5 mmHg; P=0.002) and during physical exercise testing (124.2 mmHg SD 13.4 mmHg; P=0.003). Hypertensive patients had significantly reduced values of systolic CS (P=0.001), LS (P=0.014), and SR (P<0.001) at rest as well as during physical exercise—CS (P<0.001), LS (P<0.001), and SR (P<0.001). Using STE and TDI, reduced LV systolic strain and strain rate consistent with early cardiac alterations can be detected in patients with arterial hypertension. These findings were evident at rest and markedly pronounced during exercise echocardiography