A Novel Paradigm for Sacubitril/Valsartan: Beta-Endorphin Elevation as a Contributor to Exercise Tolerance Improvement in Rats With Preexisting Heart Failure Induced by Pressure Overload

Background

Simultaneous angiotensin receptor (AT₁) blockade and neprilysin inhibition with the use of sacubitril/valsartan has been recently approved to treat patients with heart failure (HF). Therapeutic benefits of this therapy have been attributed to natriuretic peptide elevation and AT₁ receptor blockade. However, that pharmacologic picture may not be complete. The aims of this study were to investigate the pharmacology of sacubitril/valsartan compared with sacubitril and valsartan alone and to examine their impact on peptides up-regulated by neprilysin inhibition, such as beta-endorphin.

Fundamental concepts in the pathobiology of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is among the most common causes of drug-related immune-mediated thrombocytopenia. It is a unique syndrome, in that despite the fact that thrombocyto-penia is the major laboratory manifestation of HIT, its major complication is a highly morbid (and commonly fatal) thrombotic diathesis, known as the HIT with thrombosis syndrome (HITTS). The pathogenesis of HIT and HITTS has been recently elucidated, and involves an immune response against epitopes within circulating heparin-platelet factor-4 (PF4) complexes. This leads to cross-linking and activation of platelets, increasing the risk for thromboses. Furthermore, significant immunological cross-reactivity occurs between endothelial-cell bound PF4 and the HIT antibody, which may lead to endothelial damage, activation, and hyperplasia. This complex process leads to a hypercoagulable state, which may lead to overt thromboses.     

Ischemia-modified albumin improves the usefulness of standard cardiac biomarkers for the diagnosis of myocardial ischemia in the emergency department setting

We studied the role of ischemia-modified albumin (IMA) with standard biomarkers (myoglobin, creatine kinase-MB [CK-MB], troponin I [TnI]) in assessment of 200 patients with suspected myocardial ischemia admitted to the emergency department. Every case was reviewed by a cardiologist. A clinical diagnosis of ischemia was assigned and correlated with biomarker test results. Of the patients, 25 (13.0%) had myocardial ischemia. Receiver operating characteristic curves demonstrated IMA as highly sensitive but somewhat poorly specific for the presence of ischemia (area under curve, 0.63; P = .01). With a cut point of 90 U/mL, the Albumin Cobalt Binding Test had 80% sensitivity and 31% specificity for diagnosing ischemia and a negative predictive value of 92%. IMA was positive in 4 of 5 patients with electrocardiographic (ECG) evidence of ischemia and 16 of 20 patients with coronary ischemia but negative ECG. Among the same patients, the myoglobin-CK-MB-TnI triad had a sensitivity of 57%. The combination of IMA-myoglobin-CK-MB-TnI increased the sensitivity for detecting ischemia to 97%, with a negative predictive value of 92%. IMA is highly sensitive and has a high negative predictive value, which might improve the usefulness of standard biomarkers of myocardial ischemia.     

Cardiac troponin T elevation after coronary artery bypass grafting is associated with increased one-year mortality

The results of the present study extend the value of assessing troponin T for the prediction of mortality rate 1 year after coronary artery bypass grafting; this study supports previous work that demonstrated the value of postoperative assessment of troponin T for the prediction of in-hospital adverse outcome after coronary artery bypass grafting.     

Use of osseointegrated implants in the intermaxillary suture: a new possibility for the prosthetic rehabilitation of atrophic maxillae

Patients with atrophy of the maxillae, generally the elderly, are usually difficult to handle clinically, mainly due to the lack of retention, stability, and masticatory effectiveness of the total removable prosthesis. A new technique involving osseointegrated implants that are parallel to each other and arranged in the intermaxillary suture seems to provide great advantages over the current options for oral rehabilitation. This technique is quick and effective, being performed with local anesthesia and without a bone graft, and still presents low morbidity and cost.