Little is known about baseline diastolic dysfunction and changes in diastolic dysfunction grade after transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS) and its impact on overall ...outcomes. The aim of this study was to describe baseline diastolic dysfunction and changes in diastolic dysfunction grade that occur with TAVR and their relationship to mortality and rehospitalization.
This was a single-center study evaluating all TAVRs from January 2012 to June 2014. We compared parameters of diastolic dysfunction grade on pre-TAVR and 1 month post-TAVR echocardiograms for all patients undergoing the procedure. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used.
Of a sample size of 120 patients undergoing TAVR for symptomatic severe AS, 90 were included in the final analysis after excluding significant mitral valve disease. There were improvements in individual parameters of diastolic dysfunction grade such as lateral e' velocity, E/lateral e', and left atrial volume index (nonsignificant trend) in the setting of improvement in aortic valve area and gradients and functional class pre- and post-TAVR. Multivariate analysis revealed that baseline diastolic dysfunction grade, but not post-TAVR or changes in diastolic dysfunction grade, was associated with 1-year death (hazard ratio, 1.163; 95% CI, 1.049-1.277, P = .005) and combined death/cardiovascular hospitalization (hazard ratio, 1.174; 95% CI, 1.032-1.318; P = .018).
In this single-center retrospective study of patients with symptomatic severe AS who underwent TAVR, several diastolic function parameters improved on echocardiography, but baseline diastolic dysfunction grade remained the most important echocardiographic factor associated with adverse 1-year outcomes.
A key resistance mechanism to platinum-based chemotherapies and PARP inhibitors in
-mutant cancers is the acquisition of
reversion mutations that restore protein function. To estimate the prevalence ...of
reversion mutations in high-grade ovarian carcinoma (HGOC), we performed targeted next-generation sequencing of circulating cell-free DNA (cfDNA) extracted from pretreatment and postprogression plasma in patients with deleterious germline or somatic
mutations treated with the PARP inhibitor rucaparib.
reversion mutations were identified in pretreatment cfDNA from 18% (2/11) of platinum-refractory and 13% (5/38) of platinum-resistant cancers, compared with 2% (1/48) of platinum-sensitive cancers (
= 0.049). Patients without
reversion mutations detected in pretreatment cfDNA had significantly longer rucaparib progression-free survival than those with reversion mutations (median, 9.0 vs. 1.8 months; HR, 0.12;
< 0.0001). To study acquired resistance, we sequenced 78 postprogression cfDNA, identifying eight additional patients with
reversion mutations not found in pretreatment cfDNA. SIGNIFICANCE:
reversion mutations are detected in cfDNA from platinum-resistant or platinum-refractory HGOC and are associated with decreased clinical benefit from rucaparib treatment. Sequencing of cfDNA can detect multiple
reversion mutations, highlighting the ability to capture multiclonal heterogeneity.
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This study was planned by the EACVI/ASE/Industry Task Force to Standardize Deformation Imaging to (1) test the variability of speckle-tracking global longitudinal strain (GLS) measurements among ...different vendors and (2) compare GLS measurement variability with conventional echocardiographic parameters.
Sixty-two volunteers were studied using ultrasound systems from seven manufacturers. Each volunteer was examined by the same sonographer on all machines. Inter- and intraobserver variability was determined in a true test-retest setting. Conventional echocardiographic parameters were acquired for comparison. Using the software packages of the respective manufacturer and of two software-only vendors, endocardial GLS was measured because it was the only GLS parameter that could be provided by all manufactures. We compared GLSAV (the average from the three apical views) and GLS4CH (measured in the four-chamber view) measurements among vendors and with the conventional echocardiographic parameters.
Absolute values of GLSAV ranged from 18.0% to 21.5%, while GLS4CH ranged from 17.9% to 21.4%. The absolute difference between vendors for GLSAV was up to 3.7% strain units (P < .001). The interobserver relative mean errors were 5.4% to 8.6% for GLSAV and 6.2% to 11.0% for GLS4CH, while the intraobserver relative mean errors were 4.9% to 7.3% and 7.2% to 11.3%, respectively. These errors were lower than for left ventricular ejection fraction and most other conventional echocardiographic parameters.
Reproducibility of GLS measurements was good and in many cases superior to conventional echocardiographic measurements. The small but statistically significant variation among vendors should be considered in performing serial studies and reflects a reference point for ongoing standardization efforts.
Congenital heart surgery has improved the survival of patients with even the most complex defects, but the long-term survival after these procedures has not been fully described.
The purpose of this ...study was to evaluate the long-term survival of patients (age <21 years) who were operated on for congenital heart defects (CHDs).
This study used the Pediatric Cardiac Care Consortium data, a U.S.-based, multicenter registry of pediatric cardiac surgery. Survival analysis included 35,998 patients who survived their first congenital heart surgery at <21 years of age and had adequate identifiers for linkage with the National Death Index through 2014. Survival was compared to that in the general population using standardized mortality ratios (SMRs).
After a median follow-up of 18 years (645,806 person-years), 3,191 deaths occurred with an overall SMR of 8.3 (95% confidence interval CI: 8.0 to 8.7). The 15-year SMR decreased from 12.7 (95% CI: 11.9 to 13.6) in the early era (1982 to 1992) to 10.0 (95% CI: 9.3 to 10.8) in the late era (1998 to 2003). The SMR remained elevated even for mild forms of CHD such as patent ductus arteriosus (SMR 4.5) and atrial septal defects (SMR 4.9). The largest decreases in SMR occurred for patients with transposition of great arteries (early: 11.0 vs. late: 3.8; p < 0.05), complete atrioventricular canal (31.3 vs. 15.3; p < 0.05), and single ventricle (53.7 vs. 31.3; p < 0.05).
In this large U.S. cohort, long-term mortality after congenital heart surgery was elevated across all forms of CHD. Survival has improved over time, particularly for severe defects with significant changes in their management strategy, but still lags behind the general population.
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Segmentectomy for early-stage non-small cell lung cancer (NSCLC) remains controversial and has been previously associated with high local recurrence rates. We compared the outcomes of anatomic ...segmentectomy with lobectomy for stage I NSCLC and investigated the impact of surgical resection margins on recurrence.
From 2002 to 2006, 182 anatomic segmentectomies (114 open, 68 video-assisted thoracic surgery VATS), were performed for stage 1A (n = 109) or IB (n = 73) NSCLC. These were compared with 246 lobectomies (1A, 114; 1B, 132). Variables analyzed included hospital course, mortality, and patterns of recurrence and survival.
All segmentectomy surgical margins were free of tumor (average margin, 18.2 mm). Operative time (147 versus 216 minutes; p < 0.0001) and estimated blood loss (185 versus 291 mL; p = 0.0003) were significantly reduced after segmentectomy compared with lobectomy. Thirty-day mortality (1.1% versus 3.3%), total complications, disease-free recurrence, and survival were similar between segmentectomy and lobectomy at a mean follow-up of 18.1 and 28.5 months, respectively. There were 32 recurrences after segmentectomy (17.6%) at a mean of 14.3 months (14 locoregional 7.7%, 18 distant 9.9%), and 89% of recurrences were seen when tumor margins were 2 cm or less. Margin/tumor diameter ratios exceeding 1 were associated with a significant reduction in recurrence rates compared with ratios of less than 1 (25.0% versus 6.2%; p = 0.0014).
Anatomic segmentectomy can be performed safely by an open or VATS approach. Segmentectomy outcomes compare favorably with standard lobectomy for stage I NSCLC. Margin/tumor ratios of less than 1 are associated with a higher rate of recurrence. Lobectomy should be considered as primary therapy when such margins are not obtainable with segmentectomy in the good-risk patient.
Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. Advanced CF is characterized by a deficit in mucociliary ...transport (MCT), a process that traps and propels bacteria out of the lungs, but whether this deficit occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn piglets with CF. Cholinergic stimulation, which elicits mucus secretion, substantially reduced microdisk movement. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that submucosal glands and tethered mucus may be targets for early CF treatment.
Bioengineered functional brain-like cortical tissue Tang-Schomer, Min D.; White, James D.; Tien, Lee W. ...
Proceedings of the National Academy of Sciences - PNAS,
09/2014, Letnik:
111, Številka:
38
Journal Article
Recenzirano
Odprti dostop
Significance A modular 3D brain-like cortical tissue is constructed with silk protein-based scaffold and ECM composite and primary cortical neurons. This tissue responds in vitro with biochemical and ...electrophysiological outcomes, mimicking observations of brain homeostasis and mechanical injury responses.
The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.
It is well known that the solvent plays a critical role in ultrafast electron-transfer reactions. However, solvent reorganization occurs on multiple length scales, and selectively measuring ...short-range solute-solvent interactions at the atomic level with femtosecond time resolution remains a challenge. Here we report femtosecond X-ray scattering and emission measurements following photoinduced charge-transfer excitation in a mixed-valence bimetallic (Fe
Ru
) complex in water, and their interpretation using non-equilibrium molecular dynamics simulations. Combined experimental and computational analysis reveals that the charge-transfer excited state has a lifetime of 62 fs and that coherent translational motions of the first solvation shell are coupled to the back electron transfer. Our molecular dynamics simulations identify that the observed coherent translational motions arise from hydrogen bonding changes between the solute and nearby water molecules upon photoexcitation, and have an amplitude of tenths of ångströms, 120-200 cm
frequency and ~100 fs relaxation time. This study provides an atomistic view of coherent solvent reorganization mediating ultrafast intramolecular electron transfer.
This paper examines the effect on interfacial shear strength (IFSS) when grafting polyethyleneoxide (PEO) polymers of various molecular weights to a carbon fiber surface. Using copper-azide-alkyne ...cycloaddition click chemistry, PEO polymers of 1 kDa, 2 kDa, 5 kDa, and 10 kDa were tethered to the fiber surface without causing degradation of the fiber surface. The resulting IFSS increases were maximised (130% and 160%) for the 1 kDa and 10 kDa surface modified fibers, respectively. These data suggest that increases in IFSS are the result of an interplay between the density of surface modification versus the penetration of the grafted polymer into the matrix interphase. The trade-off between interphase penetration and surface grafting density is highlighted for the 2 and 5 kDa PEO chains on the fiber surface which display smaller IFSS increases (85% and 117%, respectively). Measuring the mobility of the PEO polymers by 1H NMR found an order of magnitude decrease in diffusion coefficient for each successive increase in molecular weight, supporting the hypothesis that grafting density decreases with molecular weight. Molecular dynamics simulations of the carbon fiber-matrix interface further supports these observations. These results will inform the design of complementary interfaces for various materials in a range of supporting media.
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