Amorphous boron carbide (a-BxC) networks consist of light elements, and their low atomic scattering factors makes structural analysis by x-ray diffraction difficult. Electron diffraction has an ...advantage of detecting the light elements, because of the strong interaction between the matter and electrons. In this work, we prepared a-BxC by ion beam technologies and plasma-enhanced chemical vapor deposition, and characterized their structures via atomic pair-distribution functions derived from electron diffraction intensity profiles. It was found that a pentagonal pyramid is the most favorable cluster in a-B4C generated by ion irradiation, while C—C homonuclear bonds were formed in the deposited a-BxC thin film. X-ray photoemission spectroscopy revealed that the a-BxC thin film possesses more carbon than B4C, which is responsible for the formation of the homonuclear bonds.
Although high aerobic capacity is associated with effective cardiac function, the effect of aerobic capacity on atrial function, especially in terms of cellular mechanisms, is not known. We aimed to ...investigate whether rats with low inborn maximal oxygen uptake (VO2 max) had impaired atrial myocyte contractile function when compared to rats with high inborn VO2 max.
Atrial myocyte function was depressed in Low Capacity Runners (LCR) relative to High Capacity Runners (HCR) which was associated with impaired Ca(2+) handling. Fractional shortening was 52% lower at 2 Hz and 60% lower at 5 Hz stimulation while time to 50% relengthening was 43% prolonged and 55% prolonged, respectively. Differences in Ca(2+) amplitude and diastolic Ca(2+) level were observed at 5 Hz stimulation where Ca(2+) amplitude was 70% lower and diastolic Ca(2+) level was 11% higher in LCR rats. Prolonged time to 50% Ca(2+) decay was associated with reduced sarcoplasmic reticulum (SR) Ca(2+) ATPase function in LCR (39%). Na(+)/Ca(2+) exchanger activity was comparable between the groups. Diastolic SR Ca(2+) leak was increased by 109%. This could be partly explained by increased ryanodine receptors phosphorylation at the Ca(2+)-calmodulin-dependent protein kinase-II specific Ser-2814 site in LCR rats. T-tubules were present in 68% of HCR cells whereas only 33% LCR cells had these structures. In HCR, the significantly higher numbers of cells with T-tubules were combined with greater numbers of myocytes where Ca(2+) release in the cell occurred simultaneously in central and peripheral regions, giving rise to faster and more spatial homogenous Ca(2+)-signal onset.
This data demonstrates that contrasting for low or high aerobic capacity leads to diverse functional and structural remodelling of atrial myocytes, with impaired contractile function in LCR compared to HCR rats.
Pertuzumab, a first-in-class human epidermal receptor 2 (HER2) dimerization inhibitor, is a humanized monoclonal anti-HER2 antibody that binds HER2's dimerization domain and inhibits HER2 signaling. ...Based on supporting preclinical studies, we undertook a Phase II trial of pertuzumab in patients with recurrent non-small cell lung cancer (NSCLC).
Patients with previously treated NSCLC accessible for core biopsy and naive to HER pathway inhibitors were treated with pertuzumab i.v. once every 3 weeks. Tumor assessments were done at 6 and 12 weeks and then every 3 months thereafter. The primary efficacy end point was overall response rate by Response Evaluation Criteria in Solid Tumors. Measurement of tumor glucose metabolism (SUVmax) by F-18-fluorodeoxyglucose positron emission tomography was used as an exploratory pharmacodynamic marker of drug activity.
Of 43 patients treated with pertuzumab, no responses were seen; 18 of 43 (41.9%) and 9 of 43 (20.9%) patients had stable disease at 6 and 12 weeks, respectively. The median and 3-month progression-free survival rates (PFS) were 6.1 weeks (95% confidence interval, 5.3-11.3 weeks) and 28.4% (95% confidence interval, 14.4-44.2%), respectively. Of 22 patients who underwent F-18-fluorodeoxyglucose positron emission tomography, six (27.3%) had a metabolic response to pertuzumab as evidenced by decreased SUV max. These patients had prolonged PFS (HR = 0.11, log-rank P value = 0.018) compared with the 16 patients who had no metabolic response. Four patients (9.3%) experienced a grade 3/grade 4 adverse event judged related to pertuzumab; none exhibited grade 3/grade 4 cardiac toxicity.
Pertuzumab is well tolerated as monotherapy. Pharmacodynamic activity correlated with prolonged PFS was detected in a moderate percentage of patients (27.3%). Further clinical development of pertuzumab should focus on rational combinations of pertuzumab with other drugs active in NSCLC.
This paper is devoted to present the latest results on the exploitation of the force/tactile sensor developed by the authors in terms of modeling and interpretation of the data provided by the ...device. An analytical nonlinear model of the elastically deformable sensor is derived and validated, which allows to reconstruct the position and orientation of the surface in contact with a rigid object on the basis of the sensor signals. The reconstruction is performed via an Extended Kalman Filter able to counteract the measurement noise and to handle the nonlinearity of the model at the same time. The contact plane position and orientation information together with the contact force vector measured by the sensor are used to estimate the physical parameter most relevant to manipulation control purposes: the friction coefficient. A slippage control algorithm is presented which exploits the estimated friction and a novel slipping detection algorithm is proposed to cope with the unavoidable uncertainties of the real world and its effectiveness is experimentally proved in comparison with the existing techniques.
•Force/tactile sensor modeling and data interpretation.•Contact plane pose estimation by using Extended Kalman Filter.•Friction coefficient estimation for different materials.•Experiments on slipping avoidance.•Experiments on slipping detection.
Purpose of Review
To analyze the literature on current conservative treatment options for Peyronie’s disease (PD).
Recent Findings
Conservative therapy with intralesional collagenase clostridium ...histolyticum (CCH) is safe and efficacious in either the acute or chronic phases of PD. Combination treatment with penile traction therapy (PTT) can produce even better results. While most PTT devices require extended periods of therapy up to 8 h per day, the RestoreX® device can be effective at 30–90 min per day.
Summary
A variety of conservative therapies are available for treatment of PD. The available literature does not reveal any treatment benefit of oral therapies. Intralesional therapy is the mainstay conservative treatment of PD. Intralesional CCH therapy is the first Food and Drug Administration-approved intralesional therapy and represents the authors’ preference for medical therapy. The most effective conservative management of PD likely requires a combination of therapies.
This study compares, from a prospective, observational, non-randomized registry, the post-implant hospitalization rates and associated healthcare resource utilization of cardiac resynchronization ...therapy-defibrillator (CRT-D) patients with quadripolar (QUAD) vs. bipolar (BIP) left ventricular (LV) leads.
Between January 2009 and December 2012, 193 consecutive patients receiving de novo CRT-D implants with either a QUAD (n = 116) or a BIP (n = 77) LV lead were enrolled at implant and followed until July 2013 at a single-centre, university hospital. Post-implant hospitalizations related to heart failure (HF) or LV lead surgical revision and associated payer costs were identified using ICD-9-CM diagnosis and procedure codes. Italian national reimbursement rates were determined. Propensity scores were estimated using a logistic regression model based upon 11 pre-implant baseline characteristics and were used to derive a 1 : 1 matched cohort of QUAD (n = 77) and BIP (n = 77) patients. Hospitalization rates for the two groups were compared using negative binomial regression and associated payer costs were compared using non-parametric bootstrapping (×10 000) and one-sided hypothesis test. Hospitalization rates of the QUAD group 0.15/ patient (pt)-year were lower than those of the BIP group (0.32/ pt-year); the incidence rate ratio was 0.46, P = 0.04. The hospitalization costs for the QUAD group (434 ± 128 €/pt-year) were lower than those for the BIP group (1136 ± 362 €/pt-year). The average difference was 718 €/pt-year, P = 0.016.
In this comparative effectiveness assessment of well-matched groups of CRT-D patients with quadripolar and bipolar LV leads, QUAD patients experienced a lower rate of hospitalizations for HF and LV lead surgical revision, and a lower cost burden. This has important implications for LV pacing lead choice.
Pulmonary vein antrum isolation is the most effective rhythm control strategy in patients with paroxysmal AF. However, catheter ablation of non-paroxysmal AF has a lower success rate, even when ...persistent isolation of pulmonary veins (PVs) is achieved. As a result of arrhythmia-related electophysiological and structural changes in the atria, sites other than the PVs can harbour triggers. These non-PV triggers contribute to AF relapse. In this article, we summarise the rationale and current evidence supporting the arrhythmogenic role of non-PV triggers and our ablation approach to patients with non-paroxysmal AF.
Abstract
Introduction
Having a common embryologic origin with the pulmonary veins (PVs), left atrial posterior wall (LAPW) is considered to be a source of non-PV triggers that facilitate maintenance ...of atrial fibrillation (AF). However, the benefits of electrical isolation of the posterior wall (PWI) is still debated with contradictory data originating from different ablation approaches.
Purpose
We report the distribution of triggers in the LAPW area in AF patients undergoing repeat ablation.
Methods
Consecutive AF patients undergoing catheter ablation between 2015 and 2022 were included in this analysis.
PVs were isolated first. Next, high-dose isoproterenol challenge (up to 30µg/min) was used to disclose triggers in the PW by moving the circular mapping catheter along the PW down to the level of coronary sinus, which were targeted using additional RF energy. We defined lower part of LAPW as the area between the line joining the inferior borders of the inferior PV-encircling lesions and the coronary sinus. The endpoint was to achieve electrical isolation, as documented by absence of any electrical activity in the PW.
Results
Of the 10,963 AF ablations performed during the specified time period, 6249 (57%) had triggers mapped and ablated in the LAPW area.
Triggers were seen to be originating from the part of the PW between the PVs in 4124 (66%) and from the lower part of the PW in 2125 (34%) patients. Of these, 1624 (26%) patients had focal triggers detected in both the area between the PVs and the lower PW. All triggers from in between PVs were targeted for ablation, whereas lower PW sites were ablated in 1296 (61%) and not targeted for ablation the remaining 829 (39%). Figure 1 demonstrates the triggers arising from lower PW.
At 1 year, amongst patients with lower PW triggers, 1049/1296 (81%) vs 326/829 (39.3%) (p<0.001) were arrhythmia-free.
Conclusion
Ectopic triggers in the LAPW were documented to be arising from the lower part of the PW in approximately 1/3rd of cases and ablation of those sites resulted in significantly higher success rate.
Multiple morphologies, hemodynamic instability, or noninducibility may limit ventricular tachycardia (VT) ablation in patients with arrhythmogenic right ventricular dysplasia (ARVD). Substrate-based ...mapping and ablation may overcome these limitations. We report the results and success of substrate-based VT ablation in ARVD.
Twenty-two patients with ARVD were studied. Traditional mapping for VT was limited because of multiple/changing VT morphologies (n=14), nonsustained VT (n=10), or hemodynamic intolerance (n=5). Sinus rhythm CARTO mapping was performed to define areas of "scar" (<0.5 mV) and "abnormal" myocardium (0.5 to 1.5 mV). Ablation was performed in "abnormal" regions, targeting sites with good pace maps compared with the induced VT(s). Linear lesions were created in these areas to (1) connect the scar/abnormal region to a valve continuity or other scar or (2) encircle the scar/abnormal region. Eighteen patients had implanted cardioverter defibrillators, 15 had implanted cardioverter defibrillator therapies, and 7 had sustained VT (6 with syncope). VTs (3+/-2 per patient) were induced (cycle length, 339+/-94 ms), and scar was identified in all patients. Scar areas were related to the tricuspid annulus, proximal right ventricular outflow tract, and anterior/inferior-apical walls. Lesions connected abnormal regions to the annulus (n=12) or other scars (n=4) and/or encircled abnormal regions (n=13). Per patient, a mean of 38+/-22 radiofrequency lesions was applied. Short-term success was achieved in 18 patients (82%). VT recurred in 23%, 27%, and 47% of patients after 1, 2, and 3 years' follow-up, respectively.
Substrate-based ablation of VT in ARVD can achieve a good short-term success rate. However, recurrences become increasingly common during long-term follow-up.
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