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Treatment of wounds is challenging due to bacterial infections, including Staphylococcus aureus and Pseudomonas aeruginosa. Using the merits of alternative antimicrobials like tea tree oil (TTO) and nanotechnology, they can be helpful in combatting bacterial infections. Solid lipid nanoparticle (SLN) and chitosan (CS) nanoparticles show great potential as carriers for enhancing the stability and therapeutic benefits of oils. The aim of this study is to compare the influence of nanocarriers in enhancing the antibacterial effects of TTO. The study evaluates the physicochemical and antibacterial properties of TTO-SLN and TTO-CS against P. aeruginosa and S. aureus. The TTO-SLN nanoparticles showed a clear round shape with the average diameter size of 477 nm, while the TTO-CS nanoparticles illustrated very homogeneous morphology with 144 nm size. The encapsulation efficiency for TTO-CS and TTO-SLN was ∼88.3% and 73.5%, respectively. Minimum inhibitory concentration against S. aureus and P. aeruginosa for TTO-CS, TTO-SLN, and pure TTO were 35 and 45 µg ml-1, 130 and 170 µg ml-1, and 380 and 410 µg ml-1, respectively. Since TTO-CS revealed an impressively higher antimicrobial effects in comparison with TTO-SLN and TTO alone, it can be considered as a nanocarrier that produces the same antimicrobial effects with lower required amounts of the active substance., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

The impact of left ventricle (LV) hypertrophy (LVH) regression on contractility-associated measures, the extent of residual cardiac dysfunction and prognostic implications after the initial remodeling process after transcatheter aortic valve replacement (TAVR) has not been investigated. We aimed to assess whether greater LV mass regression from pre-TAVR to 12-months after TAVR was associated with increased systolic function; and assess the prognostic value of residual LVH, systolic function and contractility-associated measures 12-months after TAVR. A total of 439 symptomatic patients were included and examined by echocardiography. LVH regression was assessed as percentage change in LV mass index (LVMi) from baseline to 12-months after TAVR. Midwall fractional shortening (mFS) and stress-corrected (SC-mFS) were used as contractility-associated measures. Primary outcome was all-cause mortality. SC-mFS increased from 0.94 (0.7) at baseline (BS) to 1.22 (0.7) (p < 0.05) 12-months after TAVR for patients with the most LVH regression, compared to patients with no LV regression (BS 1.06 (0.7) to 1.04 (0.5), NS). At 12-months after TAVR, multivariate analysis showed independent prognostic value of LVEF < 50% or GLS < 15% (HR 1.59, p = 0.049) and mFS < 14% (HR 1.99, p = 0.002) for future all cause death. LVH regression in AS after TAVR is associated with significant improvements of LV systolic function in contrast to patients without LV regression. Residual LVH and subsequent LV systolic dysfunction is substantial 12 months after TAVR and are associated with reduced survival. Impaired mFS and the combination of abnormal LVEF or GLS independently predicted all-cause mortality beyond 12 months after TAVR., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is commonly used to provide haemodynamic support for patients with severe cardiac failure. However, timing ECMO weaning remains challenging. We aimed to examine if an integrative weaning approach based on predefined haemodynamic, respiratory and echocardiographic criteria is associated with successful weaning., Methods: All patients weaned from ECMO between April 2017 and April 2019 at Aarhus University Hospital, Denmark, were consecutively enrolled. Predefined haemodynamic, respiratory and echocardiographic criteria were assessed before and during ECMO flow reduction. A weaning attempt was commenced in haemodynamic stable patients and patients remaining stable at minimal flow were weaned from ECMO. Comparisons were made between patients who met the criteria for weaning at first attempt and patients who did not meet these criteria. Patients completing a full weaning attempt with no further need for mechanical support within 24 h were defined as successfully weaned., Results: A total of 38 patients were included in the study, of whom 26 (68%) patients met the criteria for weaning. Among these patients, 25 (96%) could be successfully weaned. Successfully weaned patients were younger and had less need for inotropic support and ECMO duration was shorter. Fulfilling the weaning criteria was associated with successful weaning and both favourable 30-d survival and survival to discharge., Conclusion: An integrative weaning approach based on haemodynamic, respiratory and echocardiographic criteria may strengthen the clinical decision process in predicting successful weaning in patients receiving ECMO for refractory cardiac failure., (© 2021 Acta Anaesthesiologica Scandinavica Foundation.)

Background: Impella CP is a left ventricular pump which may serve as a circulatory support during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). Nevertheless, the survival rate and factors associated with survival in patients undergoing Impella insertion during CPR for CA are unknown., Methods: We performed a retrospective multicenter international registry of patients undergoing Impella insertion during on-going CPR for in- or out-of-hospital CA. We recorded immediate and 30-day survival with and without neurologic impairment using the cerebral performance category score and evaluated the factors associated with survival., Results: Thirty-five patients had an Impella CP implanted during CPR for CA. Refractory ventricular arrhythmias were the most frequent initial rhythm (65.7%). In total, 65.7% of patients immediately survived. At 30 days, 45.7% of patients were still alive. The 30-day survival rate without neurological impairment was 37.1%. In univariate analysis, survival was associated with both an age < 75 years and a time from arrest to CPR ≤ 5 min ( p = 0.035 and p = 0.008, respectively)., Conclusions: In our multicenter registry, Impella CP insertion during ongoing CPR for CA was associated with a 37.1% rate of 30-day survival without neurological impairment. The factors associated with survival were a young age and a time from arrest to CPR ≤ 5 min.

Aims: The aim of present study was to examine the preoperative prevalence and distribution of impaired left ventricular global longitudinal strain (LVGLS) in elderly patients with symptomatic aortic stenosis (AS) undergoing transcutaneous aortic valve replacement (TAVR) and to determine the predictive value of LVGLS on survival., Methods: We included 411 patients with symptomatic severe AS treated with TAVR during a 5-year period, where a baseline echocardiography including LVGLS assessment was available., Results: Mean age was 80.1 ± 7.1 years and aortic valve area (AVA) index 0.4 ± 0.1 cm 2 . 78 patients died during a median follow-up of 762 days. Mean left ventricular ejection fraction (LVEF) was 50 ± 13% and mean LVGLS was - 14.0%. LVEF was preserved in 60% of patients, while impaired LVGLS > - 18% was seen in 75% of the patients. Previous myocardial infarction, LVEF < 50%, LVGLS > - 14%, low gradient AS (< 4.0 m/s), tricuspid regurgitant gradient > 30 mmHg were identified as significant univariate predictors of all-cause mortality. On multivariate analysis LVGLS > - 14% (HR 1.79 [1.02-3.14], p = 0.04) was identified as the only independent variable associated with all-cause mortality. Reduced survival was observed with an impaired LVGLS > - 14% in the total population (p < 0.002) but also in patients with high AS gradient with preserved LVEF. LVGLS provided incremental prognostic value with respect to clinical characteristics, AVA and LVEF (χ 2 19.9, p = 0.006)., Conclusions: In patients with symptomatic AS undergoing TAVR, impaired LVGLS was highly prevalent despite preserved LVEF. LVGLS > - 14% was an independent predictor of all-cause mortality, and survival was reduced if LVGLS > - 14%.

BACKGROUND Transient atrial fibrillation (AF) following percutaneous patent foramen ovale (PFO) closure is common. Anticoagulation therapy should be considered in selected cases of prolonged AF after PFO closure, but guidelines do not provide clear recommendations on indication or choice of anticoagulant therapy for patients with post-procedural AF. CASE REPORT A 45-year-old woman presented with cryptogenic stroke verified by magnetic resonance imaging (MRI). Echocardiography revealed a PFO, which was closed percutaneously using a Gore septal occluder (25 mm). She was discharged on aspirin monotherapy (75 mg oral daily) according to institutional standard. Three weeks later, she presented with atrial fibrillation (AF). A direct oral anticoagulant (DOAC) (rivaroxaban 20 mg once daily) was initiated and aspirin was discontinued. After 4 months of follow-up, a routine echocardiography revealed large thrombi attached to both sides of the PFO occluder. CONCLUSIONS DOACs may be ineffective in preventing thrombus formation on device surfaces. Until more evidence has been provided, we suggest that DOACs are not routinely used for stroke prevention in patients following PFO closure or similar procedures within the first 3 months after device implantation.

Aim: To determine the diagnostic delay in patients with wild-type transthyretin cardiac amyloiodosis (ATTRwt). To determine the clinical and echocardiogtraphic characteristics of patients with an early and a late diagnosis and to study the suspected diagnoses and identification of diagnostic "red flags" before the ATTRwt diagnosis was established., Methods: In 50 consecutive patients with ATTRwt diagnosed from 2017 to 2019, clinical and echocardiographic patient characteristics were investigated based on electronic patient charts and echocardiographic database review at Aarhus University Hospital, Denmark., Results: The median diagnostic delay was 13 months (2-47 months) and a diagnostic delay above 3 months was associated with more advanced symptoms and left ventricular (LV) diastolic dysfunction at the time of the diagnosis. Thirty patients (60%) were investigated for at least two non-ATTRwt diagnoses during the time period from the first cardiac examination to the time of the confirmed diagnosis. ATTR red flags were significantly less used in patients with the longest diagnostic delay (p < 0.001). Abormal LV global longitudinal strain (LV-GLS < 18%) and apical sparring ratio (APSR ≥ 1.5) were present in 96% and 94% of the ATTRwt patients, respectively., Conclusion: The diagnostic delay in ATTRwt was substantial and a prolonged diagnostic delay was associated with more advanced symptoms and LV diastolic dysfunction at the time of the diagnosis. Established ATTR red flags are poorly utilized in the diagnostic process. Echocardiographic analysis of LV-GLS and APSR contributes significantly to the evaluation of LV myocardial performance and helps raise the suspicion of ATTRwt., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Microvascular impairment is well documented in hypertension. We investigated the effect of renal sympathetic denervation (RDN) on cardiac and peripheral microvasculature in patients with treatment-resistant essential hypertension (TRH)., Methods: A randomized, single centre, double-blinded, sham-controlled clinical trial. Fifty-eight patients with TRH (ambulatory systolic BP (ASBP) ≥ 145mmHg) despite stable treatment were randomized to RDN or SHAM. RDN was performed with the unipolar Medtronic Flex catheter. Coronary flow reserve (CFR) and coronary- and forearm minimum vascular resistance (C-Rmin and F-Rmin) were determined using transthoracic Doppler echocardiography and F-Rmin with venous occlusion plethysmography at baseline and at six-months follow-up., Results: RDN was performed with 5.3±0.2 lesions in the right renal artery and 5.4±0.2 lesions in the left. Baseline ASBP was 152±2mmHg (RDN, n=29) and 154±2mmHg (SHAM, n=29). Similar reductions in MAP were seen at follow up (-3.5±2.0 vs. -3.2±1.8, P=0.92). Baseline CFR was 2.9±0.1 (RDN) and 2.4±0.1 (SHAM), with no significant change at follow-up (0.2±0.2 vs. -0.1±0.2, P=0.57). C-Rmin was 1.9±0.3 (RDN) and 2.7±0.6 (SHAM) (mmHgmin/ml pr. 100g) and did not change significantly (0.3±0.5 vs. -0.4±0.8, P=0.48). F-Rmin was 3.6±0.2 (RDN) and 3.6±0.3 (SHAM) (mmHgmin/ml pr. 100ml tissue) and unchanged at follow-up (4.2±0.4 vs. 3.8±0.2, P=0.17). Left ventricular mass index was unchanged following RDN (-4±7 (RDN) vs. 3±5 (SHAM) (g/m 2 ) P=0.38)., Conclusion: The current study does not support positive effects of RDN on microvascular impairment in TRH., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension., Methods: ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity Flex TM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor ® -device., Results: Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. -0.6 ± 1.3 (RDN) m/s), systolic C-BP (-2 ± 17 (SHAM) vs. -8 ± 16 (RDN) mmHg), diastolic C-BP (-2 ± 9 (SHAM) vs. -5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN., Conclusions: In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.

Introduction: Mechanical circulatory support may be considered as a therapeutic option in selected patients with refractory cardiac arrest (rCA). Animal studies suggest a potential role for the Impella ® left ventricular assist device in this setting, but so far no human data have been published., Methods: Eight patients with rCA were treated with the Impella CP ® device at our institution from November 2014 to October 2015. The Impella CP ® was used at the discretion of the treating physicians in patients with rCA and pulseless electrical activity with presumed primary left ventricular failure. These patients were compared to 12 patients with cardiogenic shock also treated with the Impella device during the same period., Results: All cardiac arrests were witnessed with a no-flow time of 0min, six in-hospital and two out-of-hospital. Low-flow time was 50±52min (SD). The Impella device was successfully inserted in all patients with rCA and circulation was re-established. Survival rate to hospital discharge with good neurological outcome was similar among patients with rCA and cardiogenic shock treated with the Impella device (50% vs. 58%). Major vascular complications after Impella insertion occurred more frequently among patients with rCA compared to patients with cardiogenic shock (50% vs. 0%, P<0.05)., Conclusion: Mechanical support with the Impella CP ® device is a feasible and promising treatment option for selected patients with rCA. Further studies are warranted to determine the full potential and optimal patient selection compared to other modalities of mechanical circulatory support., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Increased sympathetic activity is important in the pathogenesis of hypertension and insulin resistance. Afferent signaling from the kidneys elevates the central sympathetic drive. We investigated the effect of catheter-based renal sympathetic denervation (RDN) on glucose metabolism, inflammatory markers, and blood pressure in nondiabetic patients with treatment-resistant hypertension. Eight subjects were included in an open-labelled study. Each patient was studied before and 6 months after RDN. Endogenous glucose production was assessed by a 3- 3 H glucose tracer, insulin sensitivity was examined by hyperinsulinemic euglycemic clamp, hormones and inflammatory markers were analyzed, and blood pressure was measured by office blood pressure readings and 24-hour ambulatory blood pressure monitoring. Insulin sensitivity ( M -value) increased nonsignificantly from 2.68 ± 0.28 to 3.07 ± 0.41 ( p = 0.12). A significant inverse correlation between the increase in M -value and BMI 6 months after RDN ( p = 0.03) was found, suggesting beneficial effects on leaner subjects. Blood pressure decreased significantly, but there were no changes in hormones, inflammatory markers, or endogenous glucose production. Our results indicate that RDN may improve insulin sensitivity in some patients with treatment-resistant hypertension, albeit confirmation of these indications of beneficial effects on leaner subjects awaits the outcome of larger randomized controlled studies.

Background: Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP., Method: We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA)., Results: We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial., Conclusion: Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Aim: Ischaemia-reperfusion injury (IRI) causes impaired endothelial function and is a major component of the adverse effects of reperfusion following myocardial infarction. Rotigaptide increases gap junction conductance via connexin-43. We tested the hypothesis that rotigaptide reduces experimental myocardial infarction size and ameliorates endothelial IRI in humans., Methods: Myocardial infarction study: porcine myocardial infarction was achieved by catheter-induced occlusion of the left anterior descending artery. In a randomized double-blind study, rotigaptide (n = 9) or placebo (n = 10) was administered intravenously as a 10 min bolus prior to reperfusion and continuously during 2 h of reperfusion. Myocardial infarction size (IS) was assessed as proportion of the area at risk (AAR). Human translational study: forearm IRI was induced in the presence or absence of intra-arterial rotigaptide. In a randomized double-blind study, forearm arterial blood flow was measured at rest and during intra-arterial infusion of acetylcholine (5-20 μg min(-1) ; n = 11) or sodium nitroprusside (2-8 mg min(-1) ; n = 10) before and after intra-arterial infusion of placebo or rotigaptide, and again following IRI., Results: Myocardial infarction study: Rotigaptide treatment was associated with a reduction of infarct size (IS/AAR[%]: 18.7 ± 4.1 [rotigaptide] vs. 43.6 ± 4.2 [placebo], P = 0.006). Human translational study: Endothelium-dependent vasodilatation to acetylcholine was attenuated after ischaemia-reperfusion in the presence of placebo (P = 0.007), but not in the presence of rotigaptide (P = NS). Endothelium-independent vasodilatation evoked by sodium nitroprusside was unaffected by IRI or rotigaptide (P = NS)., Conclusions: Rotigaptide reduces myocardial infarction size in a porcine model and protects from IRI-related endothelial dysfunction in man. Rotigaptide may have therapeutic potential in the treatment of myocardial infarction., (© 2016 The British Pharmacological Society.)

Heart failure is one of the most common causes of morbidity and mortality worldwide. When patients cease to respond adequately to optimal medical therapy mechanical circulatory support has been promising. The advent of mechanical circulatory support devices has allowed significant improvements in patient survival and quality of life for those with advanced or end-stage heart failure. We provide a general overview of current mechanical circulatory support devices encompassing options for both short- and long-term ventricular support.

Human colon tissue explant culture provides a physiologically relevant model system to study human gut biology. However, the small (20-30 mg) and complex tissue samples used present challenges for monitoring tissue stability, viability, and provision of sufficient tissue for analyses. Combining molecular profiling with explant culture has potential to overcome such limitations, permitting interrogation of complex gene regulation required to maintain gut mucosa in culture, monitor responses to culture environments and interventions. Human ex vivo colon explant gene expression profiles were assayed using an in-house custom-designed hCellMarkerPlex assay at culture time points 0, 1, 2, 4, and 14 h. Characteristic profiles of epithelial cell markers linked to differentiation, cellular polarization, and apoptosis were correlated with visible histochemical changes in explant epithelium during culture and tissue donors. The GenomeLab System provides effective assay of multiple targets not possible from small tissue samples with conventional gene expression technology platforms. This is advantageous to increase the utility of the ex vivo human colon model in applications to interrogate this complex and dynamic tissue environment for use in analytical testing.