New and old biomarkers in the differential diagnosis of lung cancer: Pro-gastrin-releasing peptide in comparison with neuron-specific enolase, carcinoembryonic antigen, and CYFRA 21-1.

Background: Testing for circulating biomarkers in lung cancer is hampered by the insufficient specificity. We aimed to assess the relative diagnostic accuracy of pro-gastrin-releasing peptide (ProGRP) for the differential diagnosis of small cell lung cancer and compare it with more conventional biomarkers. Methods: We enrolled a cohort of 390 patients with a clinical suspicion of lung cancer and for whom a histologic assessment was available. Serum or plasma samples were assessed for ProGRP, carcinoembryonic antigen, CYFRA 21-2, and neuron-specific enolase. The performance of each biomarker in discriminating the small cell lung cancer and squamous cell carcinoma/adenocarcinoma from non-malignant lung disease, and small cell lung cancer from squamous cell carcinoma/adenocarcinoma, was assayed by receiver operating characteristic curve analysis. Results: At the cut-off levels suggested by the manufacturers, ProGRP and neuron-specific enolase showed an almost identical sensitivity of 55.2% and 55.6%, respectively, in discriminating small cell lung cancer with respect to non-malignant lung disease. In order to quantify the added value of ProGRP to other conventional markers, we ran a multivariable logistic regression analysis, but the results showed that no markers improve the performance of ProGRP. Conclusions: ProGRP and neuron-specific enolase individually appear more accurate than other conventional biomarkers for small cell lung cancer, but the union of two markers does not increase the accuracy. The very small target group of patients with small cell lung cancer is a limitation of this study, which can explain why ProGRP alone does not show a sensitivity higher than neuron-specific enolase, as reported by other authors

Sanitary costs of osteoarthritis

Muscoloskeletal disorders are the first cause of disability and the second cause of permanent disablement in Italy. Osteoarthritis is the most frequent rheumatic disease and affects about 4 million Italians. In spite of that, data concerning social costs are lacking. On account of this lack we measured sanitary costs of 314 patients suffering from osteoarthritis. A retrospective, prevalence-based multicentric study was performed using a bottom-up approach. The study period was 12 months and referred to 1999. Eight percent of patients didn't take any drug for the treatment of osteoarthritis; NSAIDs were prescribed to 86.9% of patients, analgesics to 29.9%, chondroprotective drugs to 7.6%, and gastroprotective drugs to 36.9%. Total sanitary costs came to 455 euro / patient / year: 122 euro were spent on diagnostics, 293 euro on therapy and 40 euro on management of drug-related gastropathy. Since the costs of anti-inflammatory drugs came to 30 euro we calculated iatrogenic cost factor of 2.3. Moreover, the study supplied interesting informations about prescriptive habits, which differ in Italy from international guidelines for the medical treatment of OA, about patient management, because of hospitalization, which by itself absorbs 1/3 of resources, and about physiotherapy, which costs twice as much as pharmacological therapy. At last, data analysis gave the cue for suggestions on changing patients' managemen

Report on the International Colloquium on Cardio-Oncology (Rome, 12–14 March 2014)

Cardio-oncology is a relatively new discipline that focuses on the cardiovascular sequelae of anti-tumour drugs. As any other young adolescent discipline, cardio-oncology struggles to define its scientific boundaries and to identify best standards of care for cancer patients or survivors at risk of cardiovascular events. The International Colloquium on Cardio-Oncology was held in Rome, Italy, 12–14 March 2014, with the aim of illuminating controversial issues and unmet needs in modern cardio-oncology. This colloquium embraced contributions from different kind of disciplines (oncology and cardiology but also paediatrics, geriatrics, genetics, and translational research); in fact, cardio-oncology goes way beyond the merging of cardiology with oncology. Moreover, the colloquium programme did not review cardiovascular toxicity from one drug or the other, rather it looked at patients as we see them in their fight against cancer and eventually returning to everyday life. This represents the melting pot in which anti-cancer therapies, genetic backgrounds, and risk factors conspire in producing cardiovascular sequelae, and this calls for screening programmes and well-designed platforms of collaboration between one key professional figure and another. The International Colloquium on Cardio-Oncology was promoted by the Menarini International Foundation and co-chaired by Giorgio Minotti (Rome), Joseph R Carver (Philadelphia, Pennsylvania, United States), and Steven E Lipshultz (Detroit, Michigan, United States). The programme was split into five sessions of broad investigational and clinical relevance (what is cardiotoxicity?, cardiotoxicity in children, adolescents, and young adults, cardiotoxicity in adults, cardiotoxicity in special populations, and the future of cardio-oncology). Here, the colloquium chairs and all the session chairs briefly summarised what was said at the colloquium. Topics and controversies were reported on behalf of all members of the working group of the International Colloquium on Cardio-Oncology

NEW PERSPECTIVES IN DIAGNOSIS OF INTERSTITIAL LUNG DISEASE RELATED TO RHEUMATOID ARTHRITIS. VALIDATION STUDY OF AN ELECTRONIC STETHOSCOPE AND AD HOC SOFTWARE FOR DETECTION OF PULMONARY CRACKLES

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint swelling and tenderness, secondary to the immune-system dysfunction, often complicated by extra-articular manifestations. Among them, lung involvement is very frequent and interstitial lung disease (ILD) represents one of the deleterious complications of RA with impact on both therapeutic approach and overall prognosis. Nevertheless, diagnosis of ILD often remains missing or delayed. Objectives: To preliminarily evaluate the predictive value of pulmonary sound recorded by an electronic stethoscope (ES) and elaborated by an ad hoc software in identification of RA-ILD diagnosed by mean of high resolution computed tomography (HRCT) in a multicenter study. Methods: RA patients who underwent HRCT in the last 12 months were enrolled. They were all auscultated with the ES (Littmann 3200TM 3M, USA), bilaterally, at dorsal level, in at least 3 pulmonary fields (medium and basal). All tracks recorded were analyzed by a suitably developed software capable of recognizing pathological crackles in lung sounds. Results were compared with radiologic findings detected in a blind manner by an expert radiologist. Results: One hundred and six RA patients were enrolled (M/F: 1/2.5, mean age 68.7\ub110.3); among them 45 (42.5%) showed ILD at HRCT. Three patients were excluded because of a low quality of the sound recorded. The algorithm showed a sensitivity and specificity of 72.1% and 84.4%, respectively and a positive/negative predictive value of 69.1% and 86.3%, respectively. Conclusions: Despite preliminary, these data suggest an important role of ES in clinical practice for an early diagnosis of ILD in RA patients and a significant reduction of inappropriate prescription of HRCT. Since very different types of ILD can occur in course of RA, with different radiologic features and localization, proper development of the measurement setup (ES and ad hoc software for the detection of PC) could further increase its predictive value, in particular to avoid incorrect records and misdiagnosis. The routinely employment of ES and proper software, combined to clinical findings (cough, dyspnea) and respiratory lung function, could increase our ability to early identify ILD in RA patients

Magnetic Hydroxyapatite Bone Substitutes to Enhance Tissue Regeneration: Evaluation In Vitro Using Osteoblast-Like Cells and In Vivo in a Bone Defect

In case of degenerative disease or lesion, bone tissue replacement and regeneration is an important clinical goal. In particular, nowadays, critical size defects rely on the engineering of scaffolds that are 3D structural supports, allowing cellular infiltration and subsequent integration with the native tissue. Several ceramic hydroxyapatite (HA) scaffolds with high porosity and good osteointegration have been developed in the past few decades but they have not solved completely the problems related to bone defects. In the present study we have developed a novel porous ceramic composite made of HA that incorporates magnetite at three different ratios: HA/Mgn 95/5, HA/Mgn 90/10 and HA/Mgn 50/50. The scaffolds, consolidated by sintering at high temperature in a controlled atmosphere, have been analysed in vitro using human osteoblast-like cells. Results indicate high biocompatibility, similar to a commercially available HA bone graft, with no negative effects arising from the presence of magnetite or by the use of a static magnetic field. HA/Mgn 90/10 was shown to enhance cell proliferation at the early stage. Moreover, it has been implanted in vivo in a critical size lesion of the rabbit condyle and a good level of histocompatibility was observed. Such results identify this scaffold as particularly relevant for bone tissue regeneration and open new perspectives for the application of a magnetic field in a clinical setting of bone replacement, either for magnetic scaffold fixation or magnetic drug delivery

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation