The impact of nutritional status and appetite on the hospital length of stay and postoperative complications in elderly patients with severe aortic stenosis before aortic valve replacement.

INTRODUCTION: Severe aortic stenosis (AS) is associated with the reduction of physical activity and muscle mass and may be associated with decreased appetite. AIM: To assess the nutritional status and the impact of nutritional status and appetite on the hospital length of stay and postoperative complications in elderly patients with severe AS before aortic valve replacement. MATERIAL AND METHODS: Ninety-nine patients (55 male, 44 female; 74.3 ±5.2 years old) with severe AS and an indication for aortic valve replacement (AVR) were included. The nutritional status was assessed by different questionnaires (7-point Subjective Global Assessment Score - 7-SGA, full-Mini Nutritional Assessment - full-MNA) and anthropometric measurements (body mass index (BMI) kg/m(2)). Body composition was estimated using multi-frequency bioelectrical impedance analysis. Appetite was assessed by the Simplified Nutrition Assessment Questionnaire (SNAQ). RESULTS: The average BMI of patients was 28.8 ±5.8 kg/m(2). Results of the 7-SGA and f-MNA questionnaires revealed that 39 patients (39.4%) were at risk of malnutrition. The mean SNAQ score was 15.8 ±1.8. The average length of hospital stay was 10 ±5.8 days. There was a positive correlation of LOS with age (r = 0.26, p = 0.03) and a negative correlation with fat mass (kg) (r = -0.28, p = 0.04) and BMI (r = -0.22, p = 0.03). Postoperative complications were observed in 37 patients (37.4%). Patients who developed complications were older and had poorer nutritional status according to the results of the 7-SGA. CONCLUSIONS: Despite many patients undergoing AVR being overweight and obese, a considerable proportion displayed clinical signs of malnutrition. The results suggest that an assessment of nutritional status and appetite in this group of patients should be conducted regularly and that the 7-SGA scale could represent a reliable tool to assess malnutrition.

Lung exposure during simultaneous myocardial revascularization and lung surgery through median sternotomy.

Coronary artery disease is a frequent comorbidity in patients undergoing major thoracic surgery. Simultaneous operations eliminate the necessity of a second operation and, more importantly, minimize the delay in compulsory postoperative oncological therapy. We describe a relaxing incision in the contralateral pericardium, which allows for simple displacement of the heart. This maneuver improves exposure of the pulmonary hilum and middle mediastinum on the side of resection.

Toll-like receptor 3 signalling mediates angiogenic response upon shock wave treatment of ischaemic muscle.

AIMS: Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate immunity, is activated by binding double-stranded (ds) RNA. It plays a key role in inflammation, a process that is needed also for angiogenesis. We hypothesize that SWT causes cellular cavitation without damaging the target cells, thus liberating cytoplasmic RNA that in turn activates TLR3. METHODS AND RESULTS: SWT induces TLR3 and IFN-ß1 gene expression as well as RNA liberation from endothelial cells in a time-dependant manner. Conditioned medium from SWT-treated HUVECs induced TLR3 signalling in reporter cells. The response was lost when the medium was treated with RNase III to abolish dsRNAs or when TLR3 was silenced using siRNAs. In a mouse hind limb ischaemia model using wt and TLR3(-/-) mice (n = 6), SWT induced angiogenesis and arteriogenesis only in wt animals. These effects were accompanied by improved blood perfusion of treated limbs. Analysis of main molecules of the TLR3 pathways confirmed TLR3 signalling in vivo following SWT. CONCLUSION: Our data reveal a central role of the innate immune system, namely Toll-like receptor 3, to mediate angiogenesis upon release of cytoplasmic RNAs by mechanotransduction of SWT.

Shock Wave Treatment Protects From Neuronal Degeneration via a Toll-Like Receptor 3 Dependent Mechanism: Implications of a First-Ever Causal Treatment for Ischemic Spinal Cord Injury.

BACKGROUND: Paraplegia following spinal cord ischemia represents a devastating complication of both aortic surgery and endovascular aortic repair. Shock wave treatment was shown to induce angiogenesis and regeneration in ischemic tissue by modulation of early inflammatory response via Toll-like receptor (TLR) 3 signaling. In preclinical and clinical studies, shock wave treatment had a favorable effect on ischemic myocardium. We hypothesized that shock wave treatment also may have a beneficial effect on spinal cord ischemia. METHODS AND RESULTS: A spinal cord ischemia model in mice and spinal slice cultures ex vivo were performed. Treatment groups received immediate shock wave therapy, which resulted in decreased neuronal degeneration and improved motor function. In spinal slice cultures, the activation of TLR3 could be observed. Shock wave effects were abolished in spinal slice cultures from TLR3(-/-) mice, whereas the effect was still present in TLR4(-/-) mice. TLR4 protein was found to be downregulated parallel to TLR3 signaling. Shock wave-treated animals showed significantly better functional outcome and survival. The protective effect on neurons could be reproduced in human spinal slices. CONCLUSIONS: Shock wave treatment protects from neuronal degeneration via TLR3 signaling and subsequent TLR4 downregulation. Consequently, it represents a promising treatment option for the devastating complication of spinal cord ischemia after aortic repair.

Transaortic transcatheter aortic valve implantation: Results of the Polish arm of the ROUTE registry.

BACKGROUND: Transaortic (TAo) transcatheter aortic valve implantation (TAVI) is an alter-native approach in patients considered to be at high risk for classical open surgery with poor peripheral vessel access. The purpose of this study was to determine the feasibility of using TAo access for TAVI procedures employing the Edwards SAPIEN transcatheter heart valve. The primary objective was to determine overall 30-day mortality. METHODS: A total of 32 patients with severe aortic valve stenosis underwent TAo-TAVI using Edwards SAPIEN bioprostheses. Postoperative results were collected according to the Registry of the Utilization Of the TAo-TAVI approach using the Edwards SAPIEN Valve (ROUTE) study protocol. Complications were assessed using Valve Academic Research Consortium- 2 (VARC-2) criteria. RESULTS: The mean age of the population was 80.9 ± 5.2 years, with 53.1% being female. All patients received either the SAPIEN XT or the SAPIEN 3 bioprosthesis (Edwards Lifesciences). Device success was achieved in 100% of cases. One (3.25%) patient subsequently suffered an aortic dissection and required ascending aorta replacement. Paravalvular leakage was absent or mild in 26 (81%) patients, and moderate in 6 (19%) patients. Other complications included permanent pacemaker implantation in 2 (6.5%), and transient post operative delirium in 2 (6.5%) patients. The total hospital stay was 6.7 ± 2.4 days. New York Heart Association class decreased significantly on follow-up. Thirty-day mortality rate was 2 (6.5%) patients. CONCLUSIONS: Use of TAo access for TAVI procedures has a reasonable clinical outcome and is a safe alternative to the transfemoral and transapical approaches, especially for patients with high-risk peripheral vessel access.

Alteration of inflammatory response by shock wave therapy leads to reduced calcification of decellularized aortic xenografts in mice†.

OBJECTIVES: Tissue-engineered xenografts represent a promising treatment option in heart valve disease. However, inflammatory response leading to graft failure and incomplete in vitro repopulation with recipient cells remain challenging. Shock waves (SWs) were shown to modulate inflammation and to enhance re-epithelialization. We therefore aimed to investigate whether SWs could serve as a feasible adjunct to tissue engineering. METHODS: Porcine aortic pieces were decellularized using sodium deoxycholate and sodium dodecylsulphate and implanted subcutaneously into C57BL/6 mice (n = 6 per group). The treatment (shock wave therapy, SWT) group received SWs (0.1 mJ/mm(2), 500 impulses, 5 Hz) for modulation of inflammatory response directly after implantation; control animals remained untreated (CTR). Grafts were harvested 72 h and 3 weeks after implantation and analysed for inflammatory cytokines, macrophage infiltration and polarization, osteoclastic activity and calcification. Transmission electron microscopy (TEM) was performed. Endothelial cells (ECs) were treated with SWs and analysed for macrophage regulatory cytokines. In an ex vivo experimental set-up, decellularized porcine aortic valve conduits were reseeded with ECs with and without SWT (0.1 mJ/mm(2), 300 impulses, 3 Hz), fibroblasts as well as peripheral blood mononuclear cells (all human) and tested in a pulsatile flow perfusion system for cell coverage. RESULTS: Treated ECs showed an increase of macrophage migration inhibitory factor and macrophage inflammatory protein 1ß, whereas CD40 ligand and complement component C5/C5a were decreased. Subcutaneously implanted grafts showed increased mRNA levels of tumour necrosis factor α and interleukin 6 in the treatment group. Enhanced repopulation with recipient cells could be observed after SWT. Augmented macrophage infiltration and increased polarization towards M2 macrophages was observed in treated animals. Enhanced recruitment of osteoclastic cells in proximity to calcified tissue was found after SWT. Consequently, SWT resulted in decreased areas of calcification in treated animals. The reseeding experiment revealed that fibroblasts showed the best coverage compared with other cell types. Moreover, SW-treated ECs exhibited enhanced repopulation compared with untreated controls. CONCLUSIONS: SWs reduce the calcification of subcutaneously implanted decellularized xenografts via the modulation of the acute macrophage-mediated inflammatory response and improves the in vitro repopulation of decellularized grafts. It may therefore serve as a feasible adjunct to heart valve tissue engineering.

Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation.

OBJECTIVES: Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated. METHODS: Hind-limb ischemia was induced in 10-12 weeks old male C57/Bl6 wild-type mice by excision of the left femoral artery. Animals were randomly divided in a treatment group (SWT, 300 shock waves at 0.1 mJ/mm2, 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery. RESULTS: Higher gene expression and protein levels of angiogenic factors VEGF-A and PlGF, as well as their receptors Flt-1 and KDR have been found. This resulted in significantly more vessels per high-power field in SWT compared to controls. Improvement of blood perfusion in treatment animals was confirmed by laser Doppler perfusion imaging. Receptor tyrosine kinase profiler revealed significant phosphorylation of VEGF receptor 2 as an underlying mechanism of action. The effect of VEGF signaling was abolished upon incubation with a VEGFR2 inhibitor indicating that the effect is indeed VEGFR 2 dependent. CONCLUSIONS: Low energy shock wave treatment induces angiogenesis in acute ischemia via VEGF receptor 2 stimulation and shows the same promising effects as known from chronic myocardial ischemia. It may therefore develop as an adjunct to the treatment armentarium of acute muscle ischemia in limbs and myocardium.

Shock wave application to cell cultures.

Shock waves nowadays are well known for their regenerative effects. Basic research findings showed that shock waves do cause a biological stimulus to target cells or tissue without any subsequent damage. Therefore, in vitro experiments are of increasing interest. Various methods of applying shock waves onto cell cultures have been described. In general, all existing models focus on how to best apply shock waves onto cells. However, this question remains: What happens to the waves after passing the cell culture? The difference of the acoustic impedance of the cell culture medium and the ambient air is that high, that more than 99% of shock waves get reflected! We therefore developed a model that mainly consists of a Plexiglas built container that allows the waves to propagate in water after passing the cell culture. This avoids cavitation effects as well as reflection of the waves that would otherwise disturb upcoming ones. With this model we are able to mimic in vivo conditions and thereby gain more and more knowledge about how the physical stimulus of shock waves gets translated into a biological cell signal ("mechanotransduction").

Shockwave therapy differentially stimulates endothelial cells: implications on the control of inflammation via toll-Like receptor 3.

Shock wave therapy (SWT) reportedly improves ventricular function in ischemic heart failure. Angiogenesis and inflammation modulatory effects were described. However, the mechanism remains largely unknown. We hypothesized that SWT modulates inflammation via toll-like receptor 3 (TLR3) through the release of cytosolic RNA. SWT was applied to human umbilical vein endothelial cells (HUVECs) with 250 impulses, 0.08 mJ/mm(2) and 3 Hz. Gene expression of TLR3, inflammatory genes and signalling molecules was analysed at different time points by real-time polymerase chain reaction. SWT showed activation of HUVECs: enhanced expression of TLR3 and of the transporter protein for nucleic acids cyclophilin B, of pro-inflammatory cytokines cyclophilin A and interleukin-6 and of anti-inflammatory interleukin-10. No changes were found in the expression of vascular endothelial cell adhesion molecule. SWT modulates inflammation via the TLR3 pathway. The interaction between interleukin (IL)-6 and IL-10 in TLR3 stimulation can be schematically seen as a three-phase regulation over time.

Shock wave treatment induces angiogenesis and mobilizes endogenous CD31/CD34-positive endothelial cells in a hindlimb ischemia model: implications for angiogenesis and vasculogenesis.

OBJECTIVES: Shock waves have been shown to induce recruitment of intravenously injected endothelial progenitor cells to ischemic hind limbs in rats. We hypothesized that shock wave treatment as sole therapy would induce angiogenesis in this ischemia model and would lead to mobilization of endogenous endothelial (progenitor) cells. METHODS: A total of 18 rats, aged 5 weeks old, were subdivided into 3 groups: sham (n = 6), ischemic muscle with shock wave treatment (shock wave treatment group, n = 6), and without shock wave treatment (control, n = 6). Hind limb ischemia was induced by ligation of the femoral artery. Three weeks later, shock wave treatment (300 impulses at 0.1 mJ/mm(2)) was applied to the adductor muscle; the controls were left untreated. Muscle samples were analyzed using real-time polymerase chain reaction for angiogenic factors and chemoattractants for endothelial progenitor cell mobilization. Fluorescence activated cell sorting analysis of the peripheral blood was performed for CD31/CD34-positive cells. Perfusion was measured using laser Doppler imaging. Functional improvement was evaluated by walking analysis. RESULTS: Angiogenic factors/endothelial progenitor cell chemoattractants, stromal cell-derived factor-1 and vascular endothelial growth factor, were increased in the treatment group, as shown by real-time polymerase chain reaction, indicating the mobilization of endothelial progenitor cells. Fluorescence activated cell sorting analysis of the peripheral blood revealed high numbers of CD31/CD34-positive cells in the treatment group. Greater numbers of capillaries were found in the treated muscles. Blood perfusion increased markedly in the treatment group and led to functional restoration, as shown by the results from the walking analysis. CONCLUSIONS: Shock wave therapy therefore could develop into a feasible alternative to stem cell therapy in regenerative medicine, in particular for ischemic heart and limb disease.