Positive effect of the combination of multilevel contracture release and glucocorticoid treatment in Duchenne muscular dystrophy

Purpose: In the 1980s the first results of an early multilevel contracture release (MLCR) in patients suffering from progressive Duchenne muscular dystrophy (DMD) showed a positive effect on ambulation. Despite the demonstrated positive effects of prolongation of walking this treatment is not part of current guidelines. The aim of our study was to evaluate the effect of MLCR as well as its combination with glucocorticoid (GC) treatment on ambulation. Methods: Data of all boys (n = 86) with DMD treated in our outpatient department were analyzed regarding the treatment and loss of independent ambulation. In all, 23 were treated with GC only, ten were operated on, 21 received GC and underwent MLCR and 32 received neither of the two treatments. Results: The analysis of the loss of independent ambulation in our cohort showed a comparable extension of the ambulatory period between the GC-treated and MLCR-treated boys (p = 0.008 and p = 0.005, respectively). Furthermore, an additive effect of both therapies was found; patients with DMD who had both treatments were able to walk two years longer than those with only one of the two treatment options (p<0.001). Conclusion: Standard GC treatment and early MLCR in lower limbs have an independent positive effect on prolongation of ambulation in patients with DMD. In our cohort, the combination of both therapies is significantly more effective than each therapy alone. We suggest both should be offered to all DMD patients eligible. Level of evidence: III

Systemic inflammation predicts diastolic dysfunction in patients with sleep disordered breathing

Heart failure with preserved ejection fraction (HFpEF) constitutes approximately half of all patients with heart failure and causes mortality similar to heart failure with reduced ejection fraction [1]. HFpEF is highly relevant as novel evidence-based therapies emerge but treatment options remain limited [1]. Diastolic dysfunction is a hallmark of HFpEF and is also very common in up to 80% of high-risk cardiovascular patients undergoing cardiac surgery [2]. Even without overt HFpEF, echocardiographic diastolic dysfunction is independently associated with increased mortality [3]. Another important characteristic of HFpEF is the frequent presence of comorbidities, with one of the most important being sleep disordered breathing (SDB). SDB affects over one billion patients in the general population and is highly prevalent in cardiovascular high-risk patients, which underscores its high socioeconomic relevance [4]. Interestingly, SDB patients frequently exhibit diastolic dysfunction [5]; however, the underlying mechanisms remain elusive thus far [6]. In this cross-sectional experimental study, we analysed the role of inflammation and fibrosis for diastolic dysfunction in cardiovascular high-risk patients stratified by the prevalence of SDB, which may provide a groundwork for future therapeutic strategies

Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF

Aims Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality. Importantly, atrial remodelling and atrial fibrillation are frequently observed in HFpEF. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to improve clinical outcomes in HFpEF, and post-hoc analyses suggest atrial anti-arrhythmic effects. We tested if isolated human atrial cardiomyocytes from patients with HFpEF exhibit an increased Na influx, which is known to cause atrial arrhythmias, and if that is responsive to treatment with the SGTL2i empagliflozin. Methods and results Cardiomyocytes were isolated from atrial biopsies of 124 patients (82 with HFpEF) undergoing elective cardiac surgery. Na influx was measured with the Na-dye Asante Natrium Green–2 AM (ANG-2). Compared to patients without heart failure (NF), Na influx was doubled in HFpEF patients (NF vs. HFpEF: 0.21 ± 0.02 vs. 0.38 ± 0.04 mmol/L/min (N = 7 vs. 18); P = 0.0078). Moreover, late INa (measured via whole-cell patch clamp) was significantly increased in HFpEF compared to NF. Western blot and HDAC4 pulldown assay indicated a significant increase in CaMKII expression, CaMKII autophosphorylation, CaMKII activity, and CaMKIIdependent NaV1.5 phosphorylation in HFpEF compared to NF, whereas NaV1.5 protein and mRNA abundance remained unchanged. Consistently, increased Na influx was significantly reduced by treatment not only with the CaMKII inhibitor autocamtide- 2-related inhibitory peptide (AIP), late INa inhibitor tetrodotoxin (TTX) but also with sodium/hydrogen exchanger 1 (NHE1) inhibitor cariporide. Importantly, empagliflozin abolished both increased Na influx and late INa in HFpEF. Multivariate linear regression analysis, adjusting for important clinical confounders, revealed HFpEF to be an independent predictor for changes in Na handling in atrial cardiomyocytes. Conclusion We show for the first time increased Na influx in human atrial cardiomyocytes from HFpEF patients, partly due to increased late INa and enhanced NHE1-mediated Na influx. Empagliflozin inhibits Na influx and late INa, which could contribute to anti-arrhythmic effects in patients with HFpEF

Der Einfluss antizipierter Affekte auf die Aufrechterhaltung von Misserfolgshandlungen

No description supplie

The Effects of Selective Dorsal Rhizotomy on Balance and Symmetry of Gait in Children with Cerebral Palsy.

AIM:Cerebral palsy (CP) is associated with dysfunction of the upper motor neuron and results in balance problems and asymmetry during locomotion. Selective dorsal rhizotomy (SDR) is a surgical procedure that results in reduced afferent neuromotor signals from the lower extremities with the aim of improving gait. Its influence on balance and symmetry has not been assessed. The aim of this prospective cohort study was to evaluate the impact of SDR on balance and symmetry during walking. METHODS:18 children (10 girls, 8 boys; age 6 years (y) 3 months (m), SD 1y 8m) with bilateral spastic CP and Gross Motor Function Classification System levels I to II underwent gait analysis before and 6 to 12 months after SDR. Results were compared to 11 typically developing children (TDC; 6 girls, 5 boys; age 6y 6m, SD 1y 11m). To analyse balance, sway velocity, radial displacement and frequency were calculated. Symmetry ratios were calculated for balance measures and spatio-temporal parameters during walking. RESULTS:Most spatio-temporal parameters of gait, as well as all parameters of balance, improved significantly after SDR. Preoperative values of symmetry did not vary considerably between CP and TDC group and significant postoperative improvement did not occur. INTERPRETATION:The reduction of afferent signalling through SDR improves gait by reducing balance problems rather than enhancing movement symmetry

Correction: The Effects of Selective Dorsal Rhizotomy on Balance and Symmetry of Gait in Children with Cerebral Palsy.

[This corrects the article DOI: 10.1371/journal.pone.0152930.]

CP children’s and TDC characteristics.

<p>CP children’s and TDC characteristics.</p

Changes of velocity related balance parameters.

<p>Paired samples t-test for normally distributed data; TDC = typically developing children, CP = cerebral palsy, SDR = selective dorsal rhizotomy, BL = bilateral, UL = unilateral, R = right, L = left, * p = 0.000, † p = 0.001, ‡ p = 0.002, # p = 0.004, £ p = 0.006, ¥ p = 0.007.</p

Symmetry ratio of spatiotemporal and postural balance parameters.

<p>Symmetry ratio of spatiotemporal and postural balance parameters.</p