Patients with microvascular angina (MVA) often have persistence of symptoms despite full classical anti-ischemic therapy. In this study, we assessed the effect of ivabradine and ranolazine in MVA ...patients. We randomized 46 patients with stable MVA (effort angina, positive exercise stress test EST, normal coronary angiography, coronary flow reserve <2.5), who had symptoms inadequately controlled by standard anti-ischemic therapy, to ivabradine (5 mg twice daily), ranolazine (375 mg twice daily), or placebo for 4 weeks. The Seattle Angina Questionnaire (SAQ), EuroQoL scale, and EST were assessed at baseline and after treatment. Coronary microvascular dilation in response to adenosine and to cold pressor test and peripheral endothelial function (by flow-mediated dilation) were also assessed. Both drugs improved SAQ items and EuroQoL scale compared with placebo (p <0.01 for all), with ranolazine showing some more significant effects compared with ivabradine, on some SAQ items and EuroQoL scale (p <0.05). Time to 1-mm ST-segment depression and EST duration were improved by ranolazine compared with placebo. No effects on coronary microvascular function and on flow-mediated dilation were observed with drugs or placebo. In conclusion, ranolazine and ivabradine may have a therapeutic role in MVA patients with inadequate control of symptoms in combination with usual anti-ischemic therapy.
Since 2007, one-step nucleic acid amplification (OSNA) has been used as a diagnostic system for sentinel lymph node (SLN) examination in patients with breast cancer. This study aimed to define a new ...clinical cut-off of CK19 mRNA copy number based on the calculation of the risk that an axillary lymph node dissection (ALND) will be positive. We analyzed 1529 SLNs from 1140 patients with the OSNA assay and 318 patients with positive SLNs for micrometastasis (250 copies) and macrometastasis (5000 copies) underwent ALND. Axillary non-SLNs were routinely examined. ROC curves and Youden's index were performed in order to identify a new cut-off value. Logistic regression models were performed in order to compare OSNA categorical variables created on the basis of our and traditional cut-off to better identify patients who really need an axillary dissection. 69% and 31% of OSNA positive patients had a negative and positive ALND, respectively. ROC analysis identified a cut-off of 2150 CK19 mRNA copies with 95% sensitivity and 51% specificity. Positive and negative predictive values of this new cut-off were 47% and 96%, respectively. Logistic regression models indicated that the cut-off of 2150 copies better discriminates patients with node negative or positive in comparison with the conventional OSNA cut-off (p<0.0001). This cut-off identifies false positive and false negative cases and true-positive and true negative cases very efficiently, and therefore better identifies which patients really need an ALND and which patients can avoid one. This is why we suggest that the negative cut-off should be raised from 250 to 2150. Furthermore, we propose that for patients with a copy number that ranges between 2150 and 5000, there should be a multidisciplinary discussion concerning the clinical and bio-morphological features of primary breast cancer before any decision is taken on whether to perform an ALND or not.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atrial fibrillation is the most common complication after cardiac surgery and is associated with extended in-hospital stay and increased adverse outcomes, including death and stroke. Pericardial ...effusion is common after cardiac surgery and can trigger atrial fibrillation. We tested the hypothesis that posterior left pericardiotomy, a surgical manoeuvre that drains the pericardial space into the left pleural cavity, might reduce the incidence of atrial fibrillation after cardiac surgery.
In this adaptive, randomised, controlled trial, we recruited adult patients (aged ≥18 years) undergoing elective interventions on the coronary arteries, aortic valve, or ascending aorta, or a combination of these, performed by members of the Department of Cardiothoracic Surgery from Weill Cornell Medicine at the New York Presbyterian Hospital in New York, NY, USA. Patients were eligible if they had no history of atrial fibrillation or other arrhythmias or contraindications to the experimental intervention. Eligible patients were randomly assigned (1:1), stratified by CHA2DS2-VASc score and using a mixed-block randomisation approach (block sizes of 4, 6, and 8), to posterior left pericardiotomy or no intervention. Patients and assessors were blinded to treatment assignment. Patients were followed up until 30 days after hospital discharge. The primary outcome was the incidence of atrial fibrillation during postoperative in-hospital stay, which was assessed in the intention-to-treat (ITT) population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT02875405, and is now complete.
Between Sept 18, 2017, and Aug 2, 2021, 3601 patients were screened and 420 were included and randomly assigned to the posterior left pericardiotomy group (n=212) or the no intervention group (n=208; ITT population). The median age was 61·0 years (IQR 53·0–70·0), 102 (24%) patients were female, and 318 (76%) were male, with a median CHA2DS2-VASc score of 2·0 (IQR 1·0–3·0). The two groups were balanced with respect to clinical and surgical characteristics. No patients were lost to follow-up and data completeness was 100%. Three patients in the posterior left pericardiotomy group did not receive the intervention. In the ITT population, the incidence of postoperative atrial fibrillation was significantly lower in the posterior left pericardiotomy group than in the no intervention group (37 17% of 212 vs 66 32% of 208 p=0·0007; odds ratio adjusted for the stratification variable 0·44 95% CI 0·27–0·70; p=0·0005). Two (1%) of 209 patients in the posterior left pericardiotomy group and one (<1%) of 211 in the no intervention group died within 30 days after hospital discharge. The incidence of postoperative pericardial effusion was lower in the posterior left pericardiotomy group than in the no intervention group (26 12% of 209 vs 45 21% of 211; relative risk 0·58 95% CI 0·37–0·91). Postoperative major adverse events occurred in six (3%) patients in the posterior left pericardiotomy group and in four (2%) in the no intervention group. No posterior left pericardiotomy related complications were seen.
Posterior left pericardiotomy is highly effective in reducing the incidence of atrial fibrillation after surgery on the coronary arteries, aortic valve, or ascending aorta, or a combination of these without additional risk of postoperative complications.
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One of the main challenges to exploit molybdenum disulfide (MoS2) potentialities for the next-generation complementary metal oxide semiconductor (CMOS) technology is the realization of p-type or ...ambipolar field-effect transistors (FETs). Hole transport in MoS2 FETs is typically hampered by the high Schottky barrier height (SBH) for holes at source/drain contacts, due to the Fermi level pinning close to the conduction band. In this work, we show that the SBH of multilayer MoS2 surface can be tailored at nanoscale using soft O2 plasma treatments. The morphological, chemical, and electrical modifications of MoS2 surface under different plasma conditions were investigated by several microscopic and spectroscopic characterization techniques, including X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), conductive AFM (CAFM), aberration-corrected scanning transmission electron microscopy (STEM), and electron energy loss spectroscopy (EELS). Nanoscale current–voltage mapping by CAFM showed that the SBH maps can be conveniently tuned starting from a narrow SBH distribution (from 0.2 to 0.3 eV) in the case of pristine MoS2 to a broader distribution (from 0.2 to 0.8 eV) after 600 s O2 plasma treatment, which allows both electron and hole injection. This lateral inhomogeneity in the electrical properties was associated with variations of the incorporated oxygen concentration in the MoS2 multilayer surface, as shown by STEM/EELS analyses and confirmed by ab initio density functional theory (DFT) calculations. Back-gated multilayer MoS2 FETs, fabricated by self-aligned deposition of source/drain contacts in the O2 plasma functionalized areas, exhibit ambipolar current transport with on/off current ratio I on/I off ≈ 103 and field-effect mobilities of 11.5 and 7.2 cm2 V–1 s–1 for electrons and holes, respectively. The electrical behavior of these novel ambipolar devices is discussed in terms of the peculiar current injection mechanisms in the O2 plasma functionalized MoS2 surface.
The role of two- or three-field nodal dissection in the surgical treatment of esophageal and gastroesophageal junction cancer in the minimally invasive era is still controversial. This review aims to ...clarify the extension of nodal dissection in esophageal and gastroesophageal junctional cancer. A basic evidence-based analysis was designed, and seven research questions were formulated and answered with a narrative review. Reports with little or no data, single cases, small series and review articles were not included. Three-field lymph node dissection improves staging accuracy, enhances locoregional disease control and might improve survival in the group of patients with cervical and upper mediastinal metastatic lymph nodal involvement from middle and proximal-third esophageal cancer.
Molybdenum disulphide (MoS2) is currently regarded as a promising material for the next generation of electronic and optoelectronic devices. However, several issues need to be addressed to fully ...exploit its potential for field effect transistor (FET) applications. In this context, the contact resistance, R C, associated with the Schottky barrier between source/drain metals and MoS2 currently represents one of the main limiting factors for suitable device performance. Furthermore, to gain a deeper understanding of MoS2 FETs under practical operating conditions, it is necessary to investigate the temperature dependence of the main electrical parameters, such as the field effect mobility (μ) and the threshold voltage (V th). This paper reports a detailed electrical characterization of back-gated multilayer MoS2 transistors with Ni source/drain contacts at temperatures from T = 298 to 373 K, i.e., the expected range for transistor operation in circuits/systems, considering heating effects due to inefficient power dissipation. From the analysis of the transfer characteristics (I D−V G) in the subthreshold regime, the Schottky barrier height (ΦB ≈ 0.18 eV) associated with the Ni/MoS2 contact was evaluated. The resulting contact resistance in the on-state (electron accumulation in the channel) was also determined and it was found to increase with T as R C proportional to T 3.1. The contribution of R C to the extraction of μ and V th was evaluated, showing a more than 10% underestimation of μ when the effect of R C is neglected, whereas the effect on V th is less significant. The temperature dependence of μ and V th was also investigated. A decrease of μ proportional to 1/T α with α = 1.4 ± 0.3 was found, indicating scattering by optical phonons as the main limiting mechanism for mobility above room temperature. The value of V th showed a large negative shift (about 6 V) increasing the temperature from 298 to 373 K, which was explained in terms of electron trapping at MoS2/SiO2 interface states.
In this paper, nanoscale resolution scanning capacitance microscopy (SCM) and local capacitance-voltage measurements were used to probe the interfacial donor concentration in SiO2 4H-SiC systems ...annealed in N2O. Such nitrogen-based annealings are commonly employed to passivate SiO2 SiC interface traps, and result both in the incorporation of N-related donors in SiC and in the increase of the mobility in the inversion layer in 4H-SiC MOS-devices. From our SCM measurements, a spatially inhomogeneous donor distribution was observed in the SiO2 4H-SiC system subjected to N2O annealing. Hence, the effect of a phosphorus implantation before the oxide deposition and N2O annealing was also evaluated. In this case, besides an increased average donor concentration, an improvement of the lateral homogeneity of the active doping was also detected. The possible implications of such a pre-implantation doping of the near-interface region on 4H-SiC MOS-devices are discussed.
In the Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery (PALACS) trial, posterior pericardiotomy was associated with a significant reduction in ...postoperative atrial fibrillation (POAF) after cardiac surgery. We aimed to investigate the mechanisms underlying this effect.
We included PALACS patients with available echocardiographic data (n = 387/420, 92%). We tested the hypotheses that the reduction in POAF with the intervention was associated with 1) a reduction in postoperative pericardial effusion and/or 2) an effect on left atrial size and function. Spline and multivariable logistic regression analyses were used.
Most patients (n = 307, 79%) had postoperative pericardial effusions (anterior 68%, postero-lateral 51.9%). The incidence of postero-lateral effusion was significantly lower in patients undergoing pericardiotomy (37% vs 67%; P < .001). The median size of anterior effusion was comparable between patients with and without POAF (5.0 IQR 3.0–7.0 vs 5.0 IQR 3.0–7.5 mm; P = .42), but there was a nonsignificant trend towards larger postero-lateral effusion in the POAF group (5.0 IQR 3.0–9.0 vs 4.0 IQR 3.0–6.4 mm; P = .06). There was a non-linear association between postero-lateral effusion and POAF at a cut-off at 10 mm (OR 2.70; 95% CI 1.13, 6.47; P = .03) that was confirmed in multivariable analysis (OR 3.5, 95% CI 1.17, 10.58; P = 0.02). Left atrial dimension and function did not change significantly after posterior pericardiotomy.
Reduction in postero-lateral pericardial effusion is a plausible mechanism for the effect of posterior pericardiotomy in reducing POAF. Measures to reduce postoperative pericardial effusion are a promising approach to prevent POAF.
Pathophysiological mechanisms explaining the association between postoperative pericardial effusion and the occurrence of postoperative atrial fibrillation. Hb, hemoglobin; MetHb, methemoglobin; OxyHb, oxyhemoglobin; ROS, reactive oxygen species. Display omitted
Metal-oxide-semiconductor (MOS) capacitors with Al2O3 as a gate insulator are fabricated on cubic silicon carbide (3C-SiC). Al2O3 is deposited both by thermal and plasma-enhanced Atomic Layer ...Deposition (ALD) on a thermally grown 5 nm SiO2 interlayer to improve the ALD nucleation and guarantee a better band offset with the SiC. The deposited Al2O3/SiO2 stacks show lower negative shifts of the flat band voltage VFB (in the range of about −3 V) compared with the conventional single SiO2 layer (in the range of −9 V). This lower negative shift is due to the combined effect of the Al2O3 higher permittivity (ε = 8) and to the reduced amount of carbon defects generated during the short thermal oxidation process for the thin SiO2. Moreover, the comparison between thermal and plasma-enhanced ALD suggests that this latter approach produces Al2O3 layers possessing better insulating behavior in terms of distribution of the leakage current breakdown. In fact, despite both possessing a breakdown voltage of 26 V, the T-ALD Al2O3 sample is characterised by a higher current density starting from 15 V. This can be attributable to the slightly inferior quality (in terms of density and defects) of Al2O3 obtained by the thermal approach and, which also explains its non-uniform dC/dV distribution arising by SCM maps.
Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to ...evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF.
We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril/valsartan in addition to recommended therapy.
At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3⁻14.9 months) systolic blood pressure decreased from 117 ± 14 to 101 ± 12 mmHg (
< 0.0001), left ventricular ejection fraction (LVEF) increased from 27 ± 6 to 29.7 ± 7% (
< 0.0001), peak oxygen consumption (VO₂) improved from 14.6 ± 3.3 (% of predicted = 53.8 ± 14.1) to 17.2 ± 4.7 mL/kg/min (% of predicted = 64.7 ± 17.8) (
< 0.0001), minute ventilation/carbon dioxide production relationship (VE/VCO₂ Slope) decreased from 34.1 ± 6.3 to 31.7 ± 6.1 (
= 0.006), VO₂ at anaerobic threshold increased from 11.3 ± 2.6 to 12.6 ± 3.5 mL/kg/min (
= 0.007), oxygen pulse increased from 11.5 ± 3.0 to 13.4 ± 4.3 mL/kg/min (
< 0.0001), and ∆VO₂/∆Work increased from 9.2 ± 1.5 to 10.1 ± 1.8 mL/min/watt (
= 0.0002).
Sacubitril/valsartan improved exercise tolerance, LVEF, peak VO₂, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement.