Research strives to understand truths about particular phenomena, whether it be the pathophysiology of a disease process or how nursing care affects the outcomes of patients. Our knowledge is always ...evolving over time. To ensure that the information we derive from research data accurately reflects the truth about phenomena under investigation, different research methods are used. Triangulation is one method that helps increase the validity, reliability, and legitimation, which encompasses credibility, dependability, confirmability, and transferability, of research findings.1-4Triangulation is a research methods strategy that uses multiple data sources, researchers, theories, or research methods to ensure that the data, analysis, and conclusions of a research study are as comprehensive and accurate as possible. It also assists in identifying areas that need further study.2-7 Clinical researchers can use 4 types of triangulation when planning and implementing a clinical research study: (1) method triangulation; (2) investigator triangulation; (3) theory triangulation; and (4) data source triangulation.1,3,5,6Method triangulation incorporates multiple research methods to collection data. An example of this type of triangulation might involve using patient chart data, direct patient observations, and patient interviews to allow the clinical researcher to compare data, thereby providing a more complete picture than just using one method such as patient chart data.8
The intimal flap at the distal aortic anastomosis after standard aortic dissection repair creates distal anastomotic new entry, leading to false lumen (FL) pressurization and true lumen (TL) collapse ...and resulting in increased mortality, malperfusion, aortic growth, and reinterventions. The Ascyrus Medical Dissection Stent (AMDS; Ascyrus Medical, Boca Raton, FL) is a hybrid prosthesis that seals and depressurizes the FL at the distal anastomosis while expanding and pressurizing the TL.
The Dissected Aorta Repair Through Stent Implantation trial is a prospective, nonrandomized, international type A dissection trial where patients with acute DeBakey I dissections were enrolled between March 2017 and January 2019. Forty-seven patients were enrolled (median age, 62.5; 67.4% men) with a median follow-up of 631 days.
All patients underwent emergent surgical repair with successful AMDS implantation. One patient was excluded because of use in iatrogenic dissection. Overall mortality at 30 days and 1 year was 13.0% (6/46) and 19.6% (9/46), whereas new strokes occurred in 6.5% (3/46). Over 95% of vessel malperfusions resolved because of AMDS-induced TL expansion, including 3 patients with preoperative paralysis. Positive remodeling of the aortic arch occurred in 100% of cases with complete obliteration or thrombosis of the FL in 74%. In the proximal descending thoracic aorta positive remodeling occurred in 77% and complete obliteration or FL thrombosis in 53% of cases.
AMDS facilitates single-stage management of malperfusion and induces positive remodeling of the aortic arch through effective sealing of the distal anastomotic FL, depressurization of the FL with expansion, and pressurization of the TL. Importantly the use of AMDS is safe and reproducible.
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In Chapter 7, new digital timing detectors are suggested for small access bandwidth shaping pulse, and a digital quadrature imbalance correction is also included along with digital carrier phase ...recovery.
The role of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with diabetes mellitus (DM) and multivessel coronary artery disease (CAD) has been ...established by large trials; however, these trials largely excluded patients with left ventricular dysfunction (LVD).
The aim of this study was to determine whether treatment with PCI or CABG leads to improved outcomes in patients with DM, CAD, and LVD.
In this propensity-matched study, outcomes were compared for patients with CAD, DM, and LVD treated with PCI or CABG between 2004 and 2016. The primary outcome was major adverse cardiac and cerebrovascular events, defined as the composite of death, stroke, myocardial infarction, and repeat revascularization. Secondary outcomes were the individual components of the primary outcome.
PCI compared with CABG was associated with a higher risk for major adverse cardiac and cerebrovascular events in cohorts with ejection fraction (EF) 35% to 49% (p < 0.001) and <35% (p < 0.001). Treatment with PCI was associated with an increased risk for death in both the EF 35% to 49% and the EF <35% cohorts. Stroke rate did not differ between PCI and CABG in either EF cohort. PCI was associated with an increased rate of MI in the EF <35% cohort, and repeat revascularization occurred more frequently in patients treated with PCI in both the EF 35% to 49% cohort and the EF <35% cohort.
At long-term follow-up, patients with CAD, DM, and LVD treated with CABG exhibited a significantly lower incidence of major adverse cardiac and cerebrovascular events and better long-term survival over PCI, without a higher risk for stroke.
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Despite the impressive clinical activity of the second-generation antiandrogens enzalutamide and ARN-509 in patients with prostate cancer, acquired resistance invariably emerges. To identify the ...molecular mechanisms underlying acquired resistance, we developed and characterized cell lines resistant to ARN-509 and enzalutamide. In a subset of cell lines, ARN-509 and enzalutamide exhibit agonist activity due to a missense mutation (F876L) in the ligand-binding domain of the androgen receptor (AR). AR F876L is sufficient to confer resistance to ARN-509 and enzalutamide in in vitro and in vivo models of castration-resistant prostate cancer (CRPC). Importantly, the AR F876L mutant is detected in plasma DNA from ARN-509-treated patients with progressive CRPC. Thus, selective outgrowth of AR F876L is a clinically relevant mechanism of second-generation antiandrogen resistance that can potentially be targeted with next-generation antiandrogens.
A missense mutation in the ligand-binding domain of the androgen receptor F876L confers resistance to the second-generation antiandrogens enzalutamide and ARN-509 in preclinical models of AR function and prostate cancer and is detected in plasma DNA from ARN-509-treated patients with progressive disease. These results chart a new path for the discovery and development of next-generation antiandrogens that could be coupled with a blood-based companion diagnostic to guide treatment decisions.
Rapid deployment valves have been developed as a means to adjust for limitations in transcatheter aortic valve replacement and surgical aortic valve replacement for the management of aortic valve ...disease. To date, many studies have shown that although rapid deployment valves facilitate a shorter surgical aortic valve replacement, they offer no clinical benefit. The purpose of this study was to compare the outcomes of rapid deployment valves with conventional surgical aortic valve replacement.
This study was a retrospective review of all patients undergoing tissue aortic valve replacement at a single center. The majority of patients were men and aged more than 60 years. Patients were categorized into 2 groups: (1) rapid deployment valves and (2) conventional sutured valve. Inverse probability treatment weighting method was used to create a cohort of patients with similar baseline characteristics. Kaplan–Meier curves and log-rank tests were used to determine if there were statistically significant differences in outcomes. Primary outcome was all-cause mortality at 30 days, 1 year, and 5 years.
A total of 2237 patients made up the study population from 2013 to 2019. After inverse probability treatment weighting, there were 295 patients in each group. Shorter cardiopulmonary bypass and crossclamp times were found with the rapid deployment valves. No statistically significant difference was found in the primary and secondary outcomes. There was a significant difference in the rate of permanent pacemaker insertion with a 7% pacemaker rate in the rapid deployment valve group (P < .009).
The data suggest that rapid deployment valves offer no benefit in straightforward aortic valve replacement, and further study will help identify which patient population the valve is suited for.
This study is a retrospective comparison of conventional sutured valves with RDVs in SAVR. Display omitted
A distal anastomotic new entry tear (DANE) can occur at the time of surgical repair for acute type A aortic dissection (ATAAD). This study aimed to compare the occurrence of DANE following a standard ...hemiarch repair with that following a hemiarch repair with an uncovered arch dissection stent.
All patients who received a hemiarch repair or a hemiarch repair with an Ascyrus Medical Dissection Stent (AMDS) for ATAAD from 2017 to 2021 were included. Baseline and intra- and postoperative characteristics were collected. All available pre- and postoperative computed tomographic scans were analysed. The primary outcome measures were the incidence of DANE, positive aortic remodelling, mortality, and aortic reintervention rates at last follow-up.
A total of 114 patients underwent repair of Debakey I ATAAD during the study period with either an isolated hemiarch (n = 77) or a hemiarch with AMDS (n = 37). There was no significant difference in mortality (P = 0.768) or other in-hospital adverse events. During the follow-up period, DANE occurred in 43.3% (n = 26) of the isolated hemiarch group and in 11.8% (n = 4) of the hemiarch with AMDS group (P = 0.002). The incidence of false lumen thrombosis and obliteration favoured the AMDS group in the aortic arch (P = 0.029), the proximal descending thoracic aorta (P = 0.031), and level of pulmonary artery bifurcation (P = 0.044).
The incidence of DANE is significantly reduced with the addition of an AMDS at the time of hemiarch repair for ATAAD repair. Further follow-up is necessary to identify late aortic complications that may have been prevented by reducing the incidence of postoperative DANE.
Une nouvelle déchirure anastomotique distale peut survenir au moment de la réparation chirurgicale d’une dissection aortique aiguë de type A. Cette étude visait à comparer la survenue d’une nouvelle déchirure anastomotique distale après une réparation de l’hémicrosse standard et après une réparation de l’hémicrosse avec la mise en place d’une endoprothèse non couverte pour une dissection de la crosse de l’aorte.
Tous les patients qui ont subi une réparation de l’hémicrosse ou une réparation de l’hémicrosse par une endoprothèse AMDS (Ascyrus Medical Dissection Stent) pour une dissection aortique aiguë de type A entre 2017 et 2021 ont été inclus. Les caractéristiques initiales, peropératoires et postopératoires ont été recueillies. Tous les tomodensitogrammes pré- et postopératoires disponibles ont été analysés. Les principaux paramètres d’évaluation étaient l’incidence de nouvelle déchirure anastomotique distale, le remodelage aortique positif, la mortalité et le taux de réinterventions aortiques au dernier suivi.
Pendant l’étude, des dissections aortiques aiguës de type A, classées de type I selon la classification de DeBakey, ont été réparées chez un total de 114 patients (hémicrosse seule n = 77; hémicrosse avec endoprothèse AMDS n = 37). Aucune différence significative n’a été observée quant à la mortalité (p = 0,768) ou à d’autres manifestations indésirables survenues à l’hôpital. Pendant la période de suivi, des déchirures anastomotiques distales sont apparues chez 43,3 % (n = 26) des patients du groupe « hémicrosse seule » et chez 11,8 % (n = 4) des patients du groupe « hémicrosse avec endoprothèse AMDS » (p = 0,002). La fréquence de thrombose et d’oblitération de la fausse lumière a favorisé le groupe AMDS dans la crosse de l’aorte (p = 0,029), dans l’aorte thoracique descendante proximale (p = 0,031) et au niveau de la bifurcation de l’artère pulmonaire (p = 0,044).
La fréquence des déchirures anastomotiques distales est significativement réduite avec l’ajout d’une endoprothèse AMDS au moment de la réparation de l’hémicrosse pour une dissection aortique aiguë de type A. Un suivi additionnel est nécessaire pour déceler des complications aortiques tardives qui pourraient être prévenues par une réduction de la fréquence des déchirures anastomotiques distales postopératoires.
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Approximately 80% of breast cancers are estrogen receptor alpha (ER-α) positive, and although women typically initially respond well to antihormonal therapies such as tamoxifen and aromatase ...inhibitors, resistance often emerges. Although a variety of resistance mechanism may be at play in this state, there is evidence that in many cases the ER still plays a central role, including mutations in the ER leading to constitutively active receptor. Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and is active in patients who have progressed on antihormonal agents. However, fulvestrant suffers from poor pharmaceutical properties and must be administered by intramuscular injections that limit the total amount of drug that can be administered and hence lead to the potential for incomplete receptor blockade. We describe the identification and characterization of a series of small-molecule, orally bioavailable SERDs which are potent antagonists and degraders of ER-α and in which the ER-α degrading properties were prospectively optimized. The lead compound 11l (GDC-0810 or ARN-810) demonstrates robust activity in models of tamoxifen-sensitive and tamoxifen-resistant breast cancer, and is currently in clinical trials in women with locally advanced or metastatic estrogen receptor-positive breast cancer.
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