We have shown that Wnt5A increases the motility of melanoma cells. To explore cellular pathways involving Wnt5A, we compared gain-of-function (WNT5A stable transfectants) versus loss-of-function ...(siRNA knockdown) of WNT5A by microarray analysis. Increasing WNT5A suppressed the expression of several genes, which were re-expressed after small interference RNA-mediated knockdown of WNT5A. Genes affected by WNT5A include KISS-1, a metastasis suppressor, and CD44, involved in tumor cell homing during metastasis. This could be validated at the protein level using both small interference RNA and recombinant Wnt5A (rWnt5A). Among the genes up-regulated by WNT5A was the gene vimentin, associated with an epithelial to mesenchymal transition (EMT), which involves decreases in E-cadherin, due to up-regulation of the transcriptional repressor, Snail. rWnt5A treatment increases Snail and vimentin expression, and decreases E-cadherin, even in the presence of dominant-negativeTCF4, suggesting that this activation is independent of Wnt/β-catenin signaling. Because Wnt5A can signal via protein kinase C (PKC), the role of PKC in Wnt5A-mediated motility and EMT was also assessed using PKC inhibition and activation studies. Treating cells expressing low levels of Wnt5A with phorbol ester increased Snail expression inhibiting PKC in cells expressing high levels of Wnt5A decreased Snail. Furthermore, inhibition of PKC before Wnt5A treatment blocked Snail expression, implying that Wnt5A can potentiate melanoma metastasis via the induction of EMT in a PKC-dependent manner.
This study sought to compare early emergency department (ED) use of coronary computed tomography angiography (CTA) and stress echocardiography (SE) head-to-head.
Coronary CTA has been promoted as the ...early ED chest pain triage imaging method of choice, whereas SE is often overlooked in this setting and involves no ionizing radiation.
The authors randomized 400 consecutive low- to intermediate-risk ED acute chest pain patients without known coronary artery disease and a negative initial serum troponin level to immediate coronary CTA (n = 201) or SE (n = 199). The primary endpoint was hospitalization rate. Secondary endpoints were ED and hospital length of stay. Safety endpoints included cardiovascular events and radiation exposure.
Mean patient age was 55 years, with 43% women and predominantly ethnic minorities (46% Hispanics, 32% African Americans). Thirty-nine coronary CTA patients (19%) and 22 SE patients (11%) were hospitalized at presentation (difference 8%; 95% confidence interval: 1% to 15%; p = 0.026). Median ED length of stay for discharged patients was 5.4 h (interquartile range IQR: 4.2 to 6.4 h) for coronary CTA and 4.7 h (IQR: 3.5 to 6.0 h) for SE (p < 0.001). Median hospital length of stay was 58 h (IQR: 50 to 102 h) for coronary CTA and 34 h (IQR: 31 to 54 h) for SE (p = 0.002). There were 11 and 7 major adverse cardiovascular events for coronary CTA and SE, respectively (p = 0.47), over a median 24 months of follow-up. Median/mean complete initial work-up radiation exposure was 6.5/7.7 mSv for coronary CTA and 0/0.96 mSv for SE (p < 0.001).
The use of SE resulted in the hospitalization of a smaller proportion of patients with a shorter length of stay than coronary CTA and was safe. SE should be considered an appropriate option for ED chest pain triage (Stress Echocardiography and Heart Computed Tomography CT Scan in Emergency Department Patients With Chest Pain; NCT01384448).
The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more ...pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking.
To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended.
This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022.
Current and prior tobacco use.
Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer.
There were 4279 CHS participants (mean SD age, 72.8 5.6 years; 2450 57.3% women; 663 15.5% African American, 3585 83.8% White, and 31 0.7% of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race-adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers.
The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.
(1) Background: This study sought to explore how the novel coronavirus (COVID-19) pandemic affected the echocardiography (TTE) laboratory operations at a high volume medical center in New York City. ...Changes in cardiac imaging study volume, turn-around time, and abnormal findings were analyzed and compared to a pre-pandemic period. (2) Methods: Volume of all cardiac imaging studies and TTE reports between 11 March 2020 to 5 May 2020 and the same calendar period in 2019 were retrospectively identified and compared. (3) Results: During the pandemic, our center experienced a 46.72% reduction in TTEs, 82.47% reduction in transesophageal echocardiograms, 83.16% reduction in stress echo, 70.32% reduction in nuclear tests, 46.25% reduction in calcium score, 73.91% reduction in coronary computed tomography angiography, and 87.23% reduction in cardiac magnetic resonance imaging. TTE findings were overall similar between 2020 and 2019 (all
≥ 0.05), except for a significantly higher right ventricular systolic pressure in 2020 (39.8 ± 14.2 vs. 34.6 ± 11.2 mmHg,
= 0.012). (4) Conclusions: Despite encountering an influx of critically ill patients, our hospital center experienced a reduction in the number of cardiac imaging studies, which likely represents a change in both patient mindset and physician management approach.
Purpose
Late adverse myocardial remodeling after acute myocardial infarction (AMI) is strongly associated with sudden cardiac death (SCD). Cardiac magnetic resonance (CMR) performed early after AMI ...can predict late remodeling and SCD risk with moderate accuracy. This study assessed the ability of CMR-measured circumferential strain (CS) to add incremental predictive information to late gadolinium enhancement (LGE).
Methods
Patients with an AMI and LVEF < 50% were screened for inclusion. A total of 27 patients, totaling 432 myocardial segments, prospectively underwent CMR 7 ± 5 days after percutaneous coronary intervention (PCI). LGE, microvascular obstruction (MVO), and myocardial CS were measured for each segment. The primary endpoint was late segmental adverse remodeling defined as segmental wall motion score (WMS) > 1 measured by echocardiography 3 months after PCI.
Results
A total of 141 segments experienced the primary endpoint at 3 months. The mean LGE volume was higher in these segments, but LGE was also present in many segments with normal WMS (40 ± 28 versus 20 ± 26%,
p
< 0.01). Segments that met the primary endpoint also showed greater impairment of CS. Segments with both LGE > 17% and impaired CS >− 7.2% on CMR were more likely to experience late adverse remodeling (73%) as compared to segments with neither (9%,
p
< 0.001) or one abnormal parameter (36%,
p
< 0.001). CS >− 7.2% also added incremental accuracy to LGE > 17% for predicting late adverse remodeling (AUC 0.81 from 0.70,
p
< 0.001).
Conclusions
When performed early after AMI, LGE is a moderate predictor of late remodeling and CS is a powerful predictor of late myocardial remodeling. When combined, they can predict late remodeling, a surrogate of SCD, with high accuracy.
Abstract Background The aim of this meta-analysis was to compare the diagnostic accuracy of cardiac computed tomographic angiography (CCTA), stress echocardiography (SE) and radionuclide single ...photon emission computed tomography (SPECT) for the assessment of chest pain in emergency department (ED) setting. Methods A systematic review of Medline, Cochrane and Embase was undertaken for prospective clinical studies assessing the diagnostic efficacy of CCTA, SE or SPECT, as compared to intracoronary angiography (ICA) or the later presence of major adverse clinical outcomes (MACE), in patients presenting to the ED with chest pain. Standard approach and bivariate analysis were performed. Results Thirty-seven studies (15 CCTA, 9 SE, 13 SPECT) comprising a total of 7800 patients fulfilled inclusion criteria. The respective weighted mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and total diagnostic accuracy for CCTA were: 95%, 99%, 84%, 100% and 99%, for SE were: 84%, 94%, 73%, 96% and 96%, and for SPECT were: 85%, 86%, 57%, 95% and 88%. There was no significant difference between modalities in terms of NPV. Bivariate analysis revealed that CCTA had statistically greater sensitivity, specificity, PPV and overall diagnostic accuracy when compared to SE and SPECT. Conclusions All three modalities, when employed by an experienced clinician, are highly accurate. Each has its own strengths and limitations making each well suited for different patient groups. CCTA has higher accuracy than SE and SPECT, but it has many drawbacks, most importantly its lack of physiologic data.
Summary Background We sought to improve outcome in patients with childhood acute myeloid leukaemia (AML) by applying risk-directed therapy that was based on genetic abnormalities of the leukaemic ...cells and measurements of minimal residual disease (MRD) done by flow cytometry during treatment. Methods From Oct 13, 2002, to June 19, 2008, 232 patients with de-novo AML (n=206), therapy-related or myelodysplasia-related AML (n=12), or mixed-lineage leukaemia (n=14) were enrolled at eight centres. 230 patients were assigned by block, non-blinded randomisation, stratified by cytogenetic or morphological subtype, to high-dose (18 g/m2 , n=113) or low-dose (2 g/m2 , n=117) cytarabine given with daunorubicin and etoposide (ADE; induction 1). The primary aim of the study was to compare the incidence of MRD positivity of the high-dose group and the low-dose group at day 22 of induction 1. Induction 2 consisted of ADE with or without gemtuzumab ozogamicin (GO anti-CD33 monoclonal antibody); consolidation therapy included three additional courses of chemotherapy or haematopoietic stem-cell transplantation (HSCT). Levels of MRD were used to allocate GO and to determine the timing of induction 2. Both MRD and genetic abnormalities at diagnosis were used to determine the final risk classification. Low-risk patients (n=68) received five courses of chemotherapy, whereas high-risk patients (n=79), and standard-risk patients (n=69) with matched sibling donors, were eligible for HSCT (done for 48 high-risk and eight standard-risk patients). All 230 randomised patients were analysed for the primary endpoint. Other analyses were limited to the 216 patients with AML, excluding those with mixed-lineage leukaemia. This trial is closed to accrual and is registered with ClinicalTrials.gov , number NCT00136084. Findings Complete remission was achieved in 80% (173 of 216 patients) after induction 1 and 94% (203 of 216) after induction 2. Induction failures included two deaths from toxic effects and ten cases of resistant leukaemia. The introduction of high-dose versus low-dose cytarabine did not significantly lower the rate of MRD-positivity after induction 1 (34% vs 42%, p=0·17). The 6-month cumulative incidence of grade 3 or higher infection was 79·3% (SE 4·0) for patients in the high-dose group and 75·5% (4·2) for the low-dose group. 3-year event-free survival and overall survival were 63·0% (SE 4·1) and 71·1% (3·8), respectively. 80% (155 of 193) of patients achieved MRD of less than 0·1% after induction 2, and the cumulative incidence of relapse for this group was 17% (SE 3). MRD of 1% or higher after induction 1 was the only significant independent adverse prognostic factor for both event-free (hazard ratio 2·41, 95% CI 1·36–4·26; p=0·003) and overall survival (2·11, 1·09–4·11; p=0·028). Interpretation Our findings suggest that the use of targeted chemotherapy and HSCT, in the context of a comprehensive risk-stratification strategy based on genetic features and MRD findings, can improve outcome in patients with childhood AML. Funding National Institutes of Health and American Lebanese Syrian Associated Charities (ALSAC).
Background
Comparative effectiveness research (CER) has become a major focus of cardiovascular disease investigation to optimize diagnosis and treatment paradigms and decrease healthcare ...expenditures. Acute chest pain is a highly prevalent reason for evaluation in the Emergency Department (ED) that results in hospital admission for many patients and excess expense. Improvement in noninvasive diagnostic algorithms can potentially reduce unnecessary admissions.
Objective
To compare the performance of treadmill stress echocardiography (SE) and coronary computed tomography angiography (CTA) in ED chest pain patients with low‐to‐intermediate risk of significant coronary artery disease.
Design
This is a single‐center, randomized controlled trial (RCT) comparing SE and CTA head‐to‐head as the initial noninvasive imaging modality. The primary outcome measured is the incidence of hospitalization. The study is powered to detect a reduction in admissions from 28% to 15% with a sample size of 400. Secondary outcomes include length of stay in the ED/hospital and estimated cost of care. Safety outcomes include subsequent visits to the ED and hospitalizations, as well as major adverse cardiovascular events at 30 days and 1 year. Patients who do not meet study criteria or do not consent for randomization are offered entry into an observational registry.
ConclusionsThis RCT will add to our understanding of the roles of different imaging modalities in triaging patients with suspected angina. It will increase the CER evidence base comparing SE and CTA and provide insight into potential benefits and limitations of appropriate use of treadmill SE in the ED.
We investigated the relationship between parents' empathic responses prior to their children undergoing cancer treatment procedures and children's pain/distress during the procedures. We ...hypothesized: (1) parents' empathic distress would be positively associated with children's pain/distress, (2) parents' empathic concern would be negatively associated with children's pain/distress; and (3) parents' enduring dispositions and social support would be associated with their empathic responses. Parents completed: (1) measures of dispositions and perceived social support several weeks before their children underwent the procedures, and (2) state measures of empathic distress and empathic concern just before the procedures. Empathic distress was positively associated with children's pain; empathic concern was negatively associated with children's pain/distress. Predictions about dispositions and social support were also substantially confirmed.
This study sought to compare early emergency department (ED) use of coronary computed tomography angiography (CTA) and stress echocardiography (SE) head-to-head.
Coronary CTA has been promoted as the ...early ED chest pain triage imaging method of choice, whereas SE is often overlooked in this setting and involves no ionizing radiation.
The authors randomized 400 consecutive low- to intermediate-risk ED acute chest pain patients without known coronary artery disease and a negative initial serum troponin level to immediate coronary CTA (n = 201) or SE (n = 199). The primary endpoint was hospitalization rate. Secondary endpoints were ED and hospital length of stay. Safety endpoints included cardiovascular events and radiation exposure.
Mean patient age was 55 years, with 43% women and predominantly ethnic minorities (46% Hispanics, 32% African Americans). Thirty-nine coronary CTA patients (19%) and 22 SE patients (11%) were hospitalized at presentation (difference 8%; 95% confidence interval: 1% to 15%; p = 0.026). Median ED length of stay for discharged patients was 5.4 h (interquartile range IQR: 4.2 to 6.4 h) for coronary CTA and 4.7 h (IQR: 3.5 to 6.0 h) for SE (p < 0.001). Median hospital length of stay was 58 h (IQR: 50 to 102 h) for coronary CTA and 34 h (IQR: 31 to 54 h) for SE (p = 0.002). There were 11 and 7 major adverse cardiovascular events for coronary CTA and SE, respectively (p = 0.47), over a median 24 months of follow-up. Median/mean complete initial work-up radiation exposure was 6.5/7.7 mSv for coronary CTA and 0/0.96 mSv for SE (p < 0.001).
The use of SE resulted in the hospitalization of a smaller proportion of patients with a shorter length of stay than coronary CTA and was safe. SE should be considered an appropriate option for ED chest pain triage (Stress Echocardiography and Heart Computed Tomography CT Scan in Emergency Department Patients With Chest Pain; NCT01384448)
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