Using the Zwolle Risk Score at Time of Coronary Angiography to Triage Patients With ST-Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention or Thrombolysis.

Background The Zwolle Risk Score was designed to identify the risk of complications in patients with ST-segment‒elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). Its utility following PCI in STEMI treated with thrombolysis is unknown. The objective was to evaluate the safety of using the Zwolle Risk Score to triage patients with STEMI following PCI, including patients receiving thrombolysis.

Spinal Epidural Hematoma Secondary to Tenecteplase for ST-Elevation Myocardial Infarction in the Setting of Trauma and Cervical Endplate Fracture.

A 78-year-old woman presented with an inferior ST-segment elevation myocardial infarction in the setting of a fall resulting in facial trauma causing an unrecognized C6 cervical endplate fracture. After administration of tenecteplase, she developed a spinal epidural hematoma requiring intubation for airway protection and cessation of antiplatelet therapies. The need to delay coronary intervention in this setting led to a recurrent inferolateral ST-segment elevation myocardial infarction that eventually required coronary bypass grafting.

Outcomes of extracorporeal membrane oxygenation support in the cardiac catheterization laboratory.

Objectives: The aims of this single-center retrospective study were to characterize and determine predictors of 30-day survival in a cohort of patients requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO) supported cardiopulmonary resuscitation (E-CPR) in the cardiac catheterization laboratory (CCL) for cardiac arrest (CA) or refractory cardiogenic shock (CS).

Background: While safety in the CCL has improved, periprocedural mortality from CA remains high. The application of VA-ECMO is an emerging form of resuscitation with a paucity of data evaluating its use in the CCL for CA or CS.

Patent Foramen Ovale Treatment Strategies Correspond to an Index Predicting Pathogenicity.

Background: Percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic stroke (CS) may reduce the risk of recurrent stroke. By performing closure only in those with high risk of recurrent PFO related strokes, patient selection may be improved. The Risk of Paradoxical Embolism (RoPE) score is a point-based index developed to estimate the probability that the index CS was attributable to patent foramen ovale.

Patient outcomes in GuideLiner facilitated percutaneous coronary intervention stratified by the SYNTAX score: A retrospective analysis.

Objectives: To determine patient outcomes in GuideLiner facilitated percutaneous coronary intervention stratified by the SYNTAX score.

Design: Single centre retrospective cohort analysis.

Participants: A total of 540 consecutive cases facilitated by GuideLiner at a single center.

Apical hypertrophic cardiomyopathy treated as ST-elevation myocardial infarction.

Electrocardiographic changes resulting from apical hypertrophic cardiomyopathy may mimic an acute coronary syndrome. A 67-year-old Sudanese male without cardiac risk factors presented to hospital with chest pain and electrocardiographic findings of septal ST-segment elevation, ST-segment depression in V4-V6, and diffuse T-wave inversion. He was treated as an acute ST-elevation myocardial infarction with thrombolytics.

Identification of clinical candidates from the benzazepine class of histamine H3 receptor antagonists.

This Letter describes the discovery of GSK189254 and GSK239512 that were progressed as clinical candidates to explore the potential of H3 receptor antagonists as novel therapies for the treatment of Alzheimer's disease and other dementias. By carefully controlling the physicochemical properties of the benzazepine series and through the implementation of an aggressive and innovative screening strategy that employed high throughput in vivo assays to efficiently triage compounds, the medicinal chemistry effort was able to rapidly progress the benzazepine class of H3 antagonists through to the identification of clinical candidates with robust in vivo efficacy and excellent developability properties.

The discovery of the benzazepine class of histamine H3 receptor antagonists.

This Letter describes the discovery of a novel series of H3 receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H3 receptor antagonists based on the benzazepine core. Employing an H3 driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties.

The biofilm-specific antibiotic resistance gene ndvB is important for expression of ethanol oxidation genes in Pseudomonas aeruginosa biofilms.

Bacteria growing in biofilms are responsible for a large number of persistent infections and are often more resistant to antibiotics than are free-floating bacteria. In a previous study, we identified a Pseudomonas aeruginosa gene, ndvB, which is important for the formation of periplasmic glucans. We established that these glucans function in biofilm-specific antibiotic resistance by sequestering antibiotic molecules away from their cellular targets.

The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase.

Modification of the potent imidazole-based B-Raf inhibitor SB-590885 resulted in the identification of a series of furan-based derivatives with enhanced CNS penetration. One such compound, SB-699393 (17), was examined in vivo to challenge the hypothesis that selective B-Raf inhibitors may be of value in the treatment of stroke.

4-acyl-1-(4-aminoalkoxyphenyl)-2-ketopiperazines as a novel class of non-brain-penetrant histamine H3 receptor antagonists.

A series of ketopiperazines were prepared and evaluated for their activity as histamine H 3 antagonists. From investigation of the tertiary basic center in the aminopropyloxyphenyl template, the 2( R)-methylpyrrolidine was identified as the most potent amine. In the more rigid piperidineoxyphenyl template the N-cyclobutyl group was the most potent amine.

(1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: further optimisation as highly potent and selective MSK-1-inhibitors.

The novel imidazo[4,5-c]pyridine 1,2,5-oxadiazol-3-yl template affords an excellent start point for identification of inhibitors of a number of protein kinases. Here we report on its optimisation for mitogen and stress-activated protein kinase-1 (MSK-1) inhibitory activity, and selectivity over other kinases.

(1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: a novel class of potent MSK-1-inhibitors.

A novel series of imidazo[4,5-c]pyridines bearing a 1,2,5-oxadiazol-3-ylamine functionality has been developed. These are potent inhibitors of mitogen and stress-activated protein kinase-1.