Patients with a history of stable or unstable coronary heart disease have different acute phase responses to an inflammatory stimulus

Increased levels of acute phase proteins (APP) in serum are associated with vulnerability of atherosclerotic plaques and acute manifestations of coronary heart disease (CHD). APP have been viewed as indexes of active vascular inflammation or as mediators of atherothrombosis. In the present study we tested the hypothesis that individuals who develop stable or unstable forms of CHD might have different innate responses to an inflammatory stimulus. We compared changes in plasma C-reactive protein (CRP) and serum amyloid A (SAA) concentrations 48 h after a standardized inflammatory stimulus (adjuvanted influenza vaccination) in patients with quiescent CHD that had been manifested at onset as inducible myocardial ischemia (Group 1, n=26) or as acute coronary syndromes (ACS) (Group 2, n=34). Selected patients were free from inflammatory or other conditions that might affect the immune response. CRP concentration increased significantly after vaccination in both groups (Group 1: 0.47 [0.21-0.86] to 0.56 [0.32-1.17]mg/L, p=0.005; Group 2: 0.64 [0.21-1.09] to 0.75 [0.33-1.48]mg/L, p=0.003), without significant differences between groups in absolute or percentage changes. By contrast, SAA did not change after vaccination in Group 1 (14.4 [8.9-19.5] to 14.8 [10.3-18.8]mg/L, p=0.88) but increased significantly in Group 2 (16.9 [10.0-21.5] to 19.2 [11.3-29.1]mg/L, p=0.002), with significant differences between the groups in absolute and percentage terms (p=0.015 and 0.019, respectively). Changes in CRP and SAA, both absolute and percentage, were significantly correlated in Group 2 (r=0.60 and 0.66, both p<0.001). The responsiveness of plasma SAA to an inflammatory stimulus in Group 2 alone suggests a pro-inflammatory status in patients prone to acute coronary syndrome but not in those with inducible myocardial ischemia.     

ESC position paper on cardiovascular toxicity of cancer treatments: challenges and expectations

The recent position paper of the European Society of Cardiology (ESC) on cardiovascular toxicity of cancer treatments has attracted considerable interest by healthcare professionals, since it is the first concrete help in the difficult task of monitoring and approaching cardiovascular side effects of anticancer treatments. The ESC expert opinion was not intended as a clinical practice guideline; however, it reports major cardiovascular complications grouped into nine categories, addressing current clinical strategies for prevention and mitigation. In this point of view, we discuss key challenges emerging from critical appraisal of the ESC position paper: (1) the wide spectrum of cardiovascular toxicities associated with oncological drugs, focusing on targeted agents, (2) managing strategies in patients with cardiac implantable devices, (3) the underappreciated (but emerging) immune-related cardiovascular toxicities of checkpoint inhibitors, which may also result in severe heart failure and fulminant myocarditis, (4) the evolving role of anticoagulation in oncology, and the evidence supporting (or not) the use of direct-acting oral anticoagulants in cancer-associated thrombosis.     

Panencephalopathic Creutzfeldt‐Jakob Disease with Distinct Pattern of Prion Protein Deposition in a Patient with D178N Mutation and Homozygosity for Valine at Codon 129 of the Prion Protein Gene

Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53‐year‐old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt‐Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic‐type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP^Sc (Parchi classification). These findings underline the clear‐cut distinction between the neuropathological features of Creutzfeldt‐Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.