Neurologists Preferences on Basic and Advanced Cardiac Imaging Utilization in Ischemic Stroke Patients.

Introduction: It is unknown how cardiac imaging studies are used by neurologists to investigate cardioembolic sources in ischemic stroke patients.

Methods: Between August 12, 2023, and December 8, 2023, we conducted an international survey among neurologists from Europe, North America, South America, and Asia, to investigate the frequency of utilization of cardiac imaging studies for the detection of cardioembolic sources of ischemic stroke. Questions were structured into deciles of percentage utilization of transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), ECG-gated cardiac computed tomography (G-CCT), and cardiac magnetic resonance imaging (CMRI).

Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring.

Background: Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF).

Sex Differences in Outcomes Following Left Atrial Appendage Closure.

Objective: To evaluate the effects of female sex on in-hospital outcomes and to provide estimates for sex-specific prediction models of adverse outcomes following left atrial appendage closure (LAAC).

Patients And Methods: Cohort-based observational study querying the National Inpatient Sample database between October 1, 2015, and December 31, 2017. Demographics, baseline characteristics, and comorbidities were assessed with the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index score (ECS), and CHADS-VASc score.

Antisulfatase, Osteogenic, and Anticancer Activities of Steroid Sulfatase Inhibitor EO-33 in Mice.

Steroid sulfatase (STS) is a key enzyme involved in the biosynthesis of estrogens from inactive sulfated steroids. After we reported EO-33 as a potent in vitro STS inhibitor without undesirable estrogenic activity and with osteogenic properties, we are now interested in validating EO-33's in vivo potential to inhibit STS, to prevent bone deterioration, and to reduce estrogen-dependent tumor growth. A scale-up synthesis was first elaborated to prepare the multigram quantity of EO-33 needed to perform in vivo studies.

Erratum to pre-operative use of aspirin in patients undergoing coronary artery bypass grafting: a systematic review and updated meta-analysis.

[This corrects the article DOI: 10.21037/jtd.2018.

Radial versus femoral approach for saphenous vein grafts angiography and interventions.

Background: Coronary angiography and intervention to saphenous venous grafts (SVGs) remain challenging. This study aimed to investigate the feasibility and safety of the radial approach compared to femoral access in a large cohort of patients undergoing SVG angiography and intervention.

Methods: Data from 1,481 patients from Canada, United States, and Spain who underwent procedures between 2010 and 2016 were collected.

Pre-operative use of aspirin in patients undergoing coronary artery bypass grafting: a systematic review and updated meta-analysis.

Background: Aspirin therapy improves saphenous vein graft (SVG) patency in patients undergoing coronary artery bypass graft (CABG), however, its use in the pre-operative period remains controversial. Therefore, we conducted a systematic review and meta-analysis of randomized-controlled trials (RCTs) to update the evidence about risk and benefits of pre-operative aspirin therapy in patients undergoing CABG.

Methods: Electronic databases (Medline, Embase, PubMed, Cochrane Library, and Scopus) were searched to identify RCTs evaluating the effect of aspirin versus placebo/control before CABG.

Pharmacokinetic profile of PBRM in rodents, a first selective covalent inhibitor of 17β-HSD1 for breast cancer and endometriosis treatments.

The development of a covalent inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a promising approach for the treatment of hormone-dependent breast cancer and endometriosis. After reporting the steroid derivative PBRM as a first potent covalent inhibitor of 17β-HSD1 without estrogenic activity, we are now interested in studying its pharmaceutical behavior. The metabolism study in a human liver microsomal preparation showed a gradual transformation of PBRM into PBRM-O, an oxidized ketonic form of PBRM at position C17.

Insight into the mode of action and selectivity of PBRM, a covalent steroidal inhibitor of 17β-hydroxysteroid dehydrogenase type 1.

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the biosynthesis of estradiol, the major bioactive endogenous estrogen in mammals, and constitutes an interesting therapeutic target for estrogen-dependent diseases. A steroidal derivative, 3-{[(16β,17β)-3-(2-bromoethyl)-17-hydroxyestra-1,3,5(10)-trien-16-yl]methyl} benzamide (PBRM), has recently been described as a non-estrogenic, irreversible inhibitor of 17β-HSD1. However, the mode of action of this inhibitor and its selectivity profile have not yet been elucidated.

The Aminosteroid Derivative RM-133 Shows In Vitro and In Vivo Antitumor Activity in Human Ovarian and Pancreatic Cancers.

Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority.

Chemical synthesis, cytotoxicity, selectivity and bioavailability of 5α-androstane-3α,17β-diol derivatives.

Aminosteroid derivatives represent a new family of compounds with promising antiproliferative activity over different cancer cell lines. Among all the aminosteroid derivatives synthesised in our laboratory, we have identified E-37P as one of the more potent when tested in vitro. Unfortunately, the pharmacokinetic properties of E-37P decrease its effectiveness when tested in vivo.

Discovery of a non-estrogenic irreversible inhibitor of 17β-hydroxysteroid dehydrogenase type 1 from 3-substituted-16β-(m-carbamoylbenzyl)-estradiol derivatives.

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is thought to play a pivotal role in the progression of estrogen-sensitive breast cancer by transforming estrone (E1) into estradiol (E2). We designed three successive series of E2-derivatives at position C3 of the potent inhibitor 16β-(m-carbamoylbenzyl)-E2 to remove its unwanted estrogenic activity. We report the chemical synthesis and characterization of 20 new E2-derivatives, their evaluation as 17β-HSD1 inhibitors, and their proliferative (estrogenic) activity on estrogen-sensitive cells.

A new nonestrogenic steroidal inhibitor of 17β-hydroxysteroid dehydrogenase type I blocks the estrogen-dependent breast cancer tumor growth induced by estrone.

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) converts estrone (E1) into estradiol (E2) and is expressed in many steroidogenic tissues and breast cancer cell lines. Because the potent estrogen E2 stimulates the growth and development of hormone-dependent diseases, inhibition of the final step of E2 synthesis is considered a promising strategy for the treatment of breast cancer. On the basis of our previous study identifying 16β-(m-carbamoylbenzyl)-E2 (CC-156) as a lead compound for the inhibition of 17β-HSD1, we conducted a number of structural modifications to reduce its undesired residual estrogenic activity.

Crucial Role of 3-Bromoethyl in Removing the Estrogenic Activity of 17β-HSD1 Inhibitor 16β-(m-Carbamoylbenzyl)estradiol.

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) represents a promising therapeutic target for breast cancer treatment. To reduce the undesirable estrogenic activity of potent 17β-HSD1 inhibitor 16β-(m-carbamoylbenzyl)estradiol (1) (IC(50) = 27 nM), a series of analogues with a small functionalized side chain at position 3 were synthesized and tested. The 3-(2-bromoethyl)-16β-(m-carbamoylbenzyl)-estra-1,3,5(10)-trien-17β-ol (5) was found to be a potent inhibitor (IC(50) = 68 nM) for the transformation of estrone (E1) into estradiol (E2) and, most importantly, did not stimulate the proliferation of estrogen-sensitive MCF-7 cells, suggesting no estrogenic activity.

Impact of estradiol structural modifications (18-methyl and/or 17-hydroxy inversion of configuration) on the in vitro and in vivo estrogenic activity.

It is well recognized that the majority of breast cancers are initially hormone-dependent and that 17β-estradiol (17β-E2) plays a crucial role in their development and progression. For this reason, using a compound able to block a specific enzyme involved in the last steps of the biosynthesis of 17β-E2 remains a rational way to treat estrogen-dependent diseases such as breast cancer. The present study describes the biological in vitro and in vivo evaluation of a structural modification (inversion of C18-methyl group at position 13 from β to α face) of 17β-E2 (1) and 17α-estradiol (17α-E2; 2).

Synthesis and preliminary evaluation of a modified estradiol-core bearing a fused γ-lactone as non-estrogenic inhibitor of 17β-hydroxysteroid dehydrogenase type 1.

A non-estrogenic inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) was designed based on a modified 3-hydroxy-estra-1,3,5(10)-triene core having an additional five-member lactone ring and a benzamide group. The inhibitor was synthesized, fully characterized and tested for its ability to inhibit the enzyme activity. Estrogenicity was also investigated and tested on estrogen-dependent T-47D cell line.