Left Atrial Reservoir Function and Outcomes in Secondary Mitral Regurgitation

BackgroundLeft atrial (LA) size is a marker of disease severity and is related to worse outcomes in secondary mitral regurgitation (MR). The prognostic value of LA function assessed by LA reservoir strain (LARS), however, remains unknown. The aim of this study was to investigate the prognostic implications of LARS in patients with significant secondary MR.MethodsLARS was evaluated using speckle-tracking echocardiography in patients with more than mild (grade ≥ 2) secondary MR. The population was divided into two groups according to the median LARS value (9.8%). The primary end point was all-cause mortality.ResultsA total of 666 patients (mean age, 66 ± 11 years; 68% men) were included. On multivariable analysis, more severe MR was independently associated with more impaired LARS (LARS P = .001). During a median follow-up period of 5 years (interquartile range, 2-10), 383 patients (58%) died. Patients with LARS P P ConclusionsLARS is independently associated with all-cause mortality in patients with significant secondary MR and has incremental prognostic value over LA volume and left ventricular global longitudinal strain. LARS may improve risk stratification of patients with secondary MR.</p

Functional changes in the brains of social drinkers

The aim of this study was to investigate the consequences of chronic non-pathological drinking, i.e., social drinking, on brain functioning. While ERPs were recorded, social drinking participants were assessed on cognitive tasks, which were chosen because normal functioning in these tasks allegedly depends on undamaged frontal lobes. Verb generation task Two studies were described. Study 1 involved two groups of students, a moderate social drinkers group and a heavy social drinkers group. Study 2 involved three older groups of social drinkers (light, moderate and, heavy) and an excessive drinkers group (mean age approximately 50 years). Interaction effects between group and verb generation were found at one mid frontal scalp location and at two right frontal scalp locations. An expected task effect, larger amplitudes for generating than for reading at an early latency at Fz, was found in both groups in study 1, but only for the light social drinkers in study 2. The moderate, heavy and excessive drinkers in study 2 did not show this task effect. Excessive drinkers also made more retrieval errors than the heavy social drinkers and differed at right frontal (F4) ERP components from the heavy social drinkers. A third interaction effect was found at the right frontal lead F6. At F6 higher amplitude was found for generating than for reading for the moderate drinkers of study 1 and the light drinkers of study 2. Wisconsin card-sorting task In the Wisconsin card-sorting task the N1 ERP component in response to the feedback stimuli differed between groups. The light social drinkers showed a trend towards more early negativity (N1) on early trials than on late trials; this effect was significant for the moderate drinkers, but absent in the heavy and excessive groups. Other tasks In neither the continuous performance task, the visual attention task, nor the auditory odd-ball task, differences between social drinking groups were found on the various ERP components. According to the DSM-IV criteria, a subgroup of five participants in the excessive drinking group scored for alcohol dependence. Contrasting this subgroup of alcohol dependent participants with light social drinkers showed significantly smaller frontal Go P3 in the continuous performance task, and a trend towards smaller parietal P3 to attended stimuli in the visual attention task. No effects were found with respect to the auditory odd-ball task.Conclusion This study provides new insights in the effects of long-term alcohol use. We propose that the effects of alcohol use begin with very mild cognitive effects in young social drinkers, which are found at the right frontal cortex; with progressing age and alcohol use the effects become visible on more ERP components that expand to mid-frontal locations. It seems that all these effects in social drinkers are only found when the brain is challenged with more demanding or complex tasks. When participants become dependent on alcohol, also less complex and less demanding attention and inhibition tasks show effects that, in case of the visual attention task, also become more widespread, involving also parietal scalp locations

Abnormal EEG synchronisation in heavily drinking students

OBJECTIVE: In alcoholics, grey and white brain matter is damaged. In addition, functional brain connectivity as measured by EEG coherence is abnormal. We investigated whether heavily drinking students, although drinking for a shorter period than alcoholics, already show differences in functional connectivity compared to light-drinking controls. METHODS: EEG was recorded in 11 light and 11 heavy male student drinkers during eyes closed, and eyes closed plus mental rehearsal of pictures. Functional connectivity was assessed with the Synchronisation Likelihood method. RESULTS: Heavily drinking students had more synchronisation in the theta (4-8 Hz) and gamma (30-45 Hz) band than lightly drinking students during eyes closed, both with and without a mental-rehearsal task. CONCLUSIONS: Heavy student drinkers have increases in EEG synchronisation that are indicative of changes in hippocampal-neocortical connectivity. SIGNIFICANCE: Heavy student drinkers show differences in functional connectivity as compared to their lightly drinking counterparts, even though they have a relatively short drinking history

Urinary CD8(+) T-cell counts discriminate between active and inactive lupus nephritis

<p>Introduction: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Early detection of initial renal manifestations and relapses during follow-up is pivotal to prevent loss of renal function. Apart from renal biopsies, current urinary and serological diagnostic tests fail to accurately demonstrate the presence of active LN. Previously, we demonstrated that effector memory T-cells (CD45RO(+)CCR7(-);T-EM) migrate into the urine during active LN. The objective of this study was to assess the diagnostic value of urinary T-cells in comparison with traditional markers of active LN.</p><p>Methods: T-cells in the urine during active LN and remission were investigated. Twenty-two, in most cases biopsy-proven, active LN patients and 24 SLE patients without active LN were enrolled and serial measurements were performed in 16 patients.</p><p>Results: Analysis of the urinary sediment in active renal disease showed an increased number of CD8(+) T-cells and absence of these cells during remission. Enumerating T-cell counts in LN patients with a history of renal involvement was a superior marker of active LN in comparison to traditional markers, such as proteinuria and s-creatinine.</p><p>Conclusions: In conclusion, urinary T-cells, in particular CD8(+) T cells, are a promising marker to assess renal activity in LN patients, in particular in those with prior renal involvement.</p>

Regurgitant Volume/Left Ventricular End-Diastolic Volume Ratio

International audienceObjectives :The purpose of this study was to investigate the prognostic implications of the ratio of mitral regurgitant volume (RVol) to left ventricular (LV) end-diastolic volume (EDV) in patients with significant secondary mitral regurgitation (MR).Background : Quantification of secondary MR remains challenging, and its severity can be over- or underestimated when using the proximal isovelocity surface area method, which does not take LV volume into account. This limitation can be addressed by normalizing mitral RVol to LVEDV.Methods :A total of 379 patients (mean age 67 ± 11 years; 63% male) with significant (moderate and severe) secondary MR were divided into 2 groups according to the RVol/EDV ratio: RVol/EDV ≥20% (greater MR/smaller EDV) and <20% (smaller MR/larger EDV). The primary endpoint was all-cause mortality.Results :During median (interquartile range) follow-up of 50 (26 to 94) months, 199 (52.5%) patients died. When considering patients receiving medical therapy only, patients with RVol/EDV ratio ≥20% tended to have higher mortality rates than those with RVol/EDV ratio <20% (5-year estimated rates 24.1% vs. 18.4%, respectively; p = 0.077). Conversely, when considering the entire follow-up period including mitral valve interventions, patients with a higher RVol/EDV ratio (≥20%) had lower rates of all-cause mortality compared with patients with RVol/EDV ratio <20% (5-year estimated rates 39.0% vs. 44.8%, respectively; p = 0.018). On multivariable analysis, higher RVol/EDV ratio (per 5% increment as a continuous variable) was independently associated with lower all-cause mortality (0.93; p = 0.023).Conclusions :In patients with significant secondary MR treated medically, survival tended to be lower in those with a higher RVol/EDV ratio. Conversely, a higher RVol/EDV ratio was independently associated with reduced all-cause mortality. when mitral valve interventions were taken into consideration

Cell Membrane Integrity in Myotonic Dystrophy Type 1: Implications for Therapy

<div><p>Myotonic Dystrophy type 1 (DM1) is a multisystemic disease caused by toxic RNA from a <i>DMPK</i> gene carrying an expanded (CTG•CAG)n repeat. Promising strategies for treatment of DM1 patients are currently being tested. These include antisense oligonucleotides and drugs for elimination of expanded RNA or prevention of aberrant binding to RNP proteins. A significant hurdle for preclinical development along these lines is efficient systemic delivery of compounds across endothelial and target cell membranes. It has been reported that DM1 patients show elevated levels of markers of muscle damage or loss of sarcolemmal integrity in their serum and that splicing of dystrophin, an essential protein for muscle membrane structure, is abnormal. Therefore, we studied cell membrane integrity in DM1 mouse models commonly used for preclinical testing. We found that membranes in skeletal muscle, heart and brain were impermeable to Evans Blue Dye. Creatine kinase levels in serum were similar to those in wild type mice and expression of dystrophin protein was unaffected. Also in patient muscle biopsies cell surface expression of dystrophin was normal and calcium-positive fibers, indicating elevated intracellular calcium levels, were only rarely seen. Combined, our findings indicate that cells in DM1 tissues do not display compromised membrane integrity. Hence, the cell membrane is a barrier that must be overcome in future work towards effective drug delivery in DM1 therapy.</p></div