Perspectives in noninvasive imaging for chronic coronary syndromes

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future

Role of continuous glucose monitoring in diabetic patients at high cardiovascular risk. an expert-based multidisciplinary delphi consensus

Background: Continuous glucose monitoring (CGM) shows in more detail the glycaemic pattern of diabetic subjects and provides several new parameters (“glucometrics”) to assess patients’ glycaemia and consensually guide treatment. A better control of glucose levels might result in improvement of clinical outcome and reduce disease complications. This study aimed to gather an expert consensus on the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk or with heart disease. Methods: A list of 22 statements concerning type of patients who can benefit from CGM, prognostic impact of CGM in diabetic patients with heart disease, CGM use during acute cardiovascular events and educational issues of CGM were developed. Using a two-round Delphi methodology, the survey was distributed online to 42 Italian experts (21 diabetologists and 21 cardiologists) who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement. Results: Forty experts (95%) answered the survey. Every statement achieved a positive consensus. In particular, the panel expressed the feeling that CGM can be prognostically relevant for every diabetic patient (70%) and that is clinically useful also in the management of those with type 2 diabetes not treated with insulin (87.5%). The assessment of time in range (TIR), glycaemic variability (GV) and hypoglycaemic/hyperglycaemic episodes were considered relevant in the management of diabetic patients with heart disease (92.5% for TIR, 95% for GV, 97.5% for time spent in hypoglycaemia) and can improve the prognosis of those with ischaemic heart disease (100% for hypoglycaemia, 90% for hyperglycaemia) or with heart failure (87.5% for hypoglycaemia, 85% for TIR, 87.5% for GV). The experts retained that CGM can be used and can impact the short- and long-term prognosis during an acute cardiovascular event. Lastly, CGM has a recognized educational role for diabetic subjects. Conclusions: According to this Delphi consensus, the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk is promising and deserves dedicated studies to confirm the experts’ feeling

Protective Activity of Streptococcus pneumoniae Spr1875 Protein Fragments Identified Using a Phage Displayed Genomic Library

There is considerable interest in pneumococcal protein antigens capable of inducing serotype-independent immunoprotection and of improving, thereby, existing vaccines. We report here on the immunogenic properties of a novel surface antigen encoded by ORF spr1875 in the R6 strain genome. An antigenic fragment encoded by spr1875, designated R4, was identified using a Streptococcus pneumoniae phage displayed genomic library after selection with a human convalescent serum. Immunofluorescence analysis with anti-R4 antisera showed that Spr1875 was expressed on the surface of strains belonging to different serotypes. Moreover, the gene was present with little sequence variability in 27 different pneumococcal strains isolated worldwide. A mutant lacking Spr1875 was considerably less virulent than the wild type D39 strain in an intravenous mouse model of infection. Moreover, immunization with the R4 recombinant fragment, but not with the whole Spr1875 protein, induced significant protection against sepsis in mice. Lack of protection after immunization with the whole protein was related to the presence of immunodominant, non-protective epitopes located outside of the R4 fragment. In conclusion, our data indicate that Spr1875 has a role in pneumococcal virulence and is immunogenic. As the R4 fragment conferred immunoprotection from experimental sepsis, selected antigenic fragments of Spr1875 may be useful for the development of a pneumococcal protein-based vaccine

Respiratory syncyntial virus infection in a Sicilian pediatric population: risk factors, epidemiology, and severity

Respiratory syncytial virus (RSV) is the leading cause of hospitalization for lower respiratory tract infections (LRTIs) in young children worldwide. This study evaluated the epidemiological and clinical patterns of RSV infection in infants hospitalized for LRTIs in Sicily. Over a 7-month period (October 1, 2005 to April 30, 2006), all children 6 months old, with a gestational age (GA) of >36 weeks, with a birth weight of >2.50 g, with previous hospitalizations due to LRTI, with smokers in the household, and with a history of breast-feeding (p < 0.05 for each). RSV infection was associated with a higher likelihood to be admitted to neonatal intensive care units and to longer hospitalizations (p = 0.061). The collected data show that, in Sicily, RSV is an important cause of LRTIs in infants and a variety of factors, such as gender, chronological age at hospitalization, GA, birth weight, and exposure to tobacco smoke and breast-feeding may affect the prevalence of RSV-related lower respiratory tract disease and, possibly, the risk of developing asthma-like symptoms during the school year

Protective activity of a protein fragment identified by screening of a phage display genomic library of Streptococcus pneumoniae

Objective: Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The pathogenicity of pneumococci has been attributed to various virulence factors, most of which are located on its surface. The present study was undertaken to identify novel virulence factors and antigens with immunoprotective activity by using a phage display genomic library of Streptococcus pneumoniae. Methods. A lambda phage display library from the D39 S. pneumoniae strain was selected using sera from patients convalescing from invasive pneumococcal disease. For virulence studies, adult BALB/c mice (Charles River) were inoculated i.v. with the wild type D39 strain or with an equal number of CFUs from a mutant lacking spr1875 (Δspr1875). Results. Using one a convalescent serum, we selected from the phage display library an insert encoding for a fragment designated as R4, 161 amino acid in length, whose sequence matched ORF spr1875 D39 genome. This ORF encoded for a putative surface protein with a signal peptide and a LysM domain, which is found in a number of important virulence factors. To evaluate whether the spr1875 protein is involved in pneumococcal pathogenicity we constructed the Δspr1875. Using 7 x 106 CFUs for challenge, all mice inoculated with D39 died in six days, while 80% of the mice challenged with Δspr1875 survived. The R4 fragment was capable of inducing significant, albeit partial, protection in mice inoculated with a wide variety of virulent streptococcal strains. Conclusion. We have identified a novel virulence factor of S. pneumoniae that showed protective activity in a mouse model of systemic pneumococcal disease. Further studies are needed to characterize the biological activities of this antigen