318 research outputs found
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Effects of Alternating Bias Irradiation on Defects in MOS Devices
Determinants of a successful problem list to support the implementation of the problem-oriented medical record according to recent literature
Background: A problem-oriented approach is one of the possibilities to organize a medical record. The problem-oriented medical record (POMR) - a structured organization of patient information per presented medical problem- was introduced at the end of the sixties by Dr. Lawrence Weed to aid dealing with the multiplicity of patient problems. The problem list as a precondition is the centerpiece of the problem-oriented medical record (POMR) also called problem-oriented record (POR). Prior to the digital era, paper records presented a flat list of medical problems to the healthcare professional without the features that are possible with current technology. In modern EHRs a POMR based on a structured problem list can be used for clinical decision support, registries, order management, population health, and potentially other innovative functionality in the future, thereby providing a new incentive to the implementation and use of the POMR. Methods: On both 12 May 2014 and 1 June 2015 a systematic literature search was conducted. From the retrieved articles statements regarding the POMR and related to successful or non-successful implementation, were categorized. Generic determinants were extracted from these statements. Results: In this research 38 articles were included. The literature analysis led to 12 generic determinants: clinical practice/reasoning, complete and accurate problem list, data structure/content, efficiency, functionality, interoperability, multi-disciplinary, overview of patient information, quality of care
Post hoc analyses of SHIFT and PARADIGM-HF highlight the importance of chronic Chagas' cardiomyopathy Comment on: “Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial” by Bocchi et al.
No abstract available
Long-term follow-up of quality of life in high-risk patients undergoing transcatheter aortic valve implantation for symptomatic aortic valve stenosis
Background Transcatheter aortic valve implantation (TAVI) has become the standard treatment for patients with severe symptomatic aortic stenosis (AS) considered at very high risk for surgical aortic valve replacement. The purpose of this sub-study was to evaluate long-term (> 4 years) health-related quality of life (QoL) in octogenarians who underwent TAVI. Methods A single center observational registry in twenty patients who underwent frame analysis assessment = 4 years after TAVI. Health-related QoL was evaluated, using the Short Form-36 (SF-36), the EuroQoL-5D (EQ-5D) and the visual analogue score (EQ-VAS) questionnaires. Results The mean SF-36 subscale scores at follow-up were physical functioning 40.8 ± 26.3, role physical functioning 67.7 ± 34.9, vitality 54.6 ± 21.6, general health 52.1 ± 20.4, social functioning 63.8 ± 37.7, role emotional functioning 70.2 ± 36.0, mental health 73.2 ± 23.3 and bodily pain 80.9 ± 22.9. The mean EQ-VAS score > 4 years after TAVI was 64.7 ± 15.1. With respect to functional class, 80% of the patients were in NYHA class I/II at follow-up compared to 15% prior to TAVI. Conclusions This sub-study reports a significant improvement in functional class (NYHA) in a selected group of very elderly patients > 4 years after TAVI. Furthermore, all patients showed a satisfactory QoL despite their age and multiple comorbidities. In addition, our study reveals a lower QoL when compared with the general age matched Dutch population
Comparison of Oxidative Properties, Light Absorbance, and Total and Elemental Mass Concentration of Ambient PM(2.5) Collected at 20 European Sites
OBJECTIVE: It has been proposed that the redox activity of particles may represent a major determinant of their toxicity. We measured the in vitro ability of ambient fine particles [particulate matter with aerodynamic diameters ≤2.5 μm (PM(2.5))] to form hydroxyl radicals ((•)OH) in an oxidant environment, as well as to deplete physiologic antioxidants (ascorbic acid, glutathione) in the naturally reducing environment of the respiratory tract lining fluid (RTLF). The objective was to examine how these toxicologically relevant measures were related to other PM characteristics, such as total and elemental mass concentration and light absorbance. DESIGN: Gravimetric PM(2.5) samples (n = 716) collected over 1 year from 20 centers participating in the European Community Respiratory Health Survey were available. Light absorbance of these filters was measured with reflectometry. PM suspensions were recovered from filters by vortexing and sonication before dilution to a standard concentration. The oxidative activity of these particle suspensions was then assessed by measuring their ability to generate (•)OH in the presence of hydrogen peroxide, using electron spin resonance and 5,5-dimethyl-1-pyrroline-N-oxide as spin trap, or by establishing their capacity to deplete antioxidants from a synthetic model of the RTLF. RESULTS AND CONCLUSION: PM oxidative activity varied significantly among European sampling sites. Correlations between oxidative activity and all other characteristics of PM were low, both within centers (temporal correlation) and across communities (annual mean). Thus, no single surrogate measure of PM redox activity could be identified. Because these novel measures are suggested to reflect crucial biologic mechanisms of PM, their use may be pertinent in epidemiologic studies. Therefore, it is important to define the appropriate methods to determine oxidative activity of PM
Fractional flow reserve guided percutaneous coronary intervention optimization directed by high-definition intravascular ultrasound versus standard of care
Background Post percutaneous coronary intervention (PCI) fractional flow reserve (FFR) is a significant predictor of
major adverse cardiac events (MACE). The rationale for low post procedural FFR values often remains elusive based on
angiographic findings alone, warranting further assessment using an FFR pullback or additional intravascular imaging. It is
currently unknown if additional interventions intended to improve the PCI, decrease MACE rates.
Study design The FFR REACT trial is a prospective, single-center randomized controlled trial in which 290 patients with
a post PCI FFR b0.90 will be randomized (1:1) to either standard of care (no additional intervention) or intravascular
ultrasound (IVUS)-directed optimization of the FFR (treatment arm). Eligible patients are those treated with angiographically
successful PCI for (un)stable angina or non-ST elevation myocardial infarction (MI). Assuming 45% of patients will have a post
PCI FFR b0.90, approximately 640 patients undergoing PCI will need to be enrolled. Patients with a post PCI FFR ≥ 0.90 will
be enrolled in a prospective registry. The primary end point is defined as a composite of cardiac death, target vessel MI and
clinically driven target vessel revascularisation (target vessel failure) at 1 year. Secondary end points will consist of individual
components of the primary end point, procedural success, stent thrombosis and correlations on clinical outcome, changes in
post PCI Pd/Pa and FFR and IVUS derived dimensions. All patients will be followed for 3 years.
Conclusion The FFR-REACT trial is designed to explore the potential benefit of HD-IVUS-guided PCI optimization in
patients with a post PCI FFR b0.90 (Dutch trial register: NTR6711). (Am Heart J 2019;213:66-72.
Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor
BACKGROUND: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts. METHODS: Included were MBC patients with a HER2-negative primary tumor, with ≥1 detectable CTC, starting a new line of treatment. CTCs were enumerated using the CellSearch system, characterized for HER2 with the CellSearch anti-HER2 phenotyping reagent, and characterized for ER mRNA expression. Primary end point was pr
Pharmacological activation of LXR alters the expression profile of tumor-associated macrophages and the abundance of regulatory T cells in the tumor microenvironment
Liver X receptors (LXR) are transcription factors from the nuclear receptor family that are activated by oxysterols and synthetic high-affinity agonists. In this study, we assessed the anti-tumor effects of synthetic LXR agonist TO901317 in a murine model of syngeneic Lewis Lung carcinoma. Treatment with TO901317 inhibited tumor growth in wild-type but not in LXR-deficient mice, indicating that the anti-tumor effects of the agonist depends on functional LXR activity in host cells. Pharmacological activation of the LXR pathway reduced the intratumoral abundance of regulatory T cells (Treg) and the expression of the Treg-attracting chemokine Ccl17 by MHCIIhigh tumor-associated macrophages (TAM). Moreover, gene expression profiling indicated a broad negative impact of the LXR agonist on other mechanisms used by TAM for the maintenance of an immunosuppressive environment. In studies exploring the macrophage response to GM-CSF or IL-4, activated LXR repressed IRF4 expression, resulting in subsequent downregulation of IRF4-dependent genes including Ccl17. Taken together, this work reveals the combined actions of the LXR pathway in the control of TAM responses that contribute to the anti-tumoral effects of pharmacological LXR activation. Moreover, these data provide new insights for the development of novel therapeutic options for the treatment of cancer
Estrogen receptor mutations and splice variants determined in liquid biopsies from metastatic breast cancer patients
Mutations and splice variants in the estrogen receptor (ER) gene, ESR1, may yield endocrine resistance in metastatic breast cancer (MBC) patients. These putative endocrine resistance markers are likely to emerge during treatment, and therefore, its detection in liquid biopsies, such as circulating tumor cells (CTCs) and cell-free DNA (cfDNA), is of great interest. This research aimed to determine whether ESR1 mutations and splice variants occur more frequently in CTCs of MBC patients progressing on endocrine treatment. In addition, the presence of ESR1 mutations was evaluated in matched cfDNA and compared to CTCs. CellSearch-enriched CTC fractions (≥5/7.5 mL) of two MBC cohorts were evaluated, namely (a) patients starting first-line endocrine therapy (n = 43, baseline cohort) and (b) patients progressing on any line of endocrine therapy (n = 40, progressing cohort). ESR1 hotspot mutations (D538G and Y537S/N/C) were evaluated in CTC-enriched DNA using digital PCR and compared with matched cfDNA (n = 18 baseline cohort; n = 26 progressing cohort). Expression of ESR1 full-length and 4 of its splice variants ((increment)5, (increment)7, 36 kDa, and 46 kDa) was evaluated in CTC-enriched mRNA. It was observed that in the CTCs, the ESR1 mutations were not enriched in the progressing cohort (8%), when compared with the baseline cohort (5%) (P = 0.66). In the cfDNA, however, ESR1 mutations were more prevalent in the progressing cohort (42%) than in the baseline cohort (11%) (P = 0.04). Three of the same mutations were observed in both CTCs and cfDNA, 1 mutation in CTCs only, and 11 in cfDNA only. Only the (increment)5 ESR1 splice variant was CTC-specific expressed, but was not enriched in the progressing cohort. In conclusion, sensitivity for detecting ESR1 mutations in CTC-enriched fractions was lower than for cfDNA. ESR1 mutations detected in cfDNA, rarely present at the start of first-line endocrine therapy, were enriched at progression, strongly suggesting a role in conferring endocrine resistance in MBC
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