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Background: Hemophilic arthropathy is the consequence of recurrent joint bleeds in patients affected by severe hemophilia A or B or von Willebrand disease, leading to functional limitations and chronic pain with negative impact on quality of life. Main target joints are knees, ankles, and elbows. Few therapeutic options are available for ankle arthropathy. Temporary symptom improvements have been reported by repeated (i.e., 3–5) intra-articular administrations of hyaluronic acid (HA). A non-animal stabilized very-high molecular weight HA formulation (NASHA) has been proven to achieve long-term benefits in patients with knee and hip osteoarthritis. Methods: Patients with ankle arthropathy undergoing a single NASHA (Durolane 0.5 ml, Smith & Nephew) injection were prospectively studied. Clinical assessment, including Gilbert Score (Pain, PGS, and physical examination, PEGS), pain scores (Visual Anologue scale, VAS and McGill Score, MGS), generic quality-of-life evaluation (EQ5D), and magnetic resonance imaging (MRI) were performed at baseline (T0) and 1 (T1), 6 (T6), and 12 (T12)months after NASHA injection. Results: Fifteen ankles in 9 patients (7 severe, 2 moderate; age: 21–45 years) were treated. A significant improvement of symptoms and functional outcome was reported at T1 compared to T0 (PGS: 0.5 ± 0.6 vs. 1.7 ± 1.0, P = 0.03; PEGS: 2.2 ± 2.8 vs. 4.7 ± 3.3, P = 0.001; VAS: 18 ± 19 vs. 71 ± 26; MGS: 0.8 ± 0.7 vs. 2.8 ± 1.1; P < 0.001; EQ5D: 80 ± 14 vs. 54 ± 25, P = 0.015). Data were not statistically different at T6 versus T1, suggesting long-term benefits after NASHA injection. Only 4 patients reached T12 at the time of this paper. The positive-experienced outcomes led to repeat treatment in these 4 patients 13 months (mean) after the first injection. No significant change in the European magnetic resonance imaging Score was found throughout the study. Conclusions: NASHA viscosupplementation enabled long-lasting clinical benefits and improvements of quality-of-life in patients with ankle arthropathy. This single-injection treatment provides an approach reducing risks and costs of multiple intra-articular injections, is well accepted by patients, and has a favourable cost-utility ratio.

Opposed to whole wheat (WWP), traditional pizza (TP) is loved by patients with type 1 diabetes mellitus (T1DM) despite causing hyperglycemia. 50 well-trained T1DM patients had higher glucose levels after TP than after WWP or mixed flour pizza, which however was tasty, digestible and metabolically appropriate to break diet monotony.

Lipohypertophy (LH) is the most common skin complication of incorrect injection technique which does not only represent an aesthetic defect but also severely disrupts insulin pharmacokinetics/pharmacodynamics. As a consequence of that, hormone release is delayed and unexplained/unpredictable hypoglycemia occurs, both deteriorating metabolic control while negatively affecting adherence to treatment and quality of life. The economic burden due to unwanted intra-LH injections is accounted for by inappropriately high insulin requirements, increased emergency-related hospitalizations, and loss of work days. Greater attention has to be paid by diabetes care teams to education programs with periodic refreshers to achieve better metabolic control and reduce the economic burden of diabetes.

Background: Although patients with idiopathic VTE are at higher than normal risk of asymptomatic atherosclerosis and of cardiovascular events, the impact of cardiovascular risk factors on VTE is poorly understood. Objective: To assess the prevalence of the metabolic syndrome and of its components in patients with early-onset idiopathic VTE. Methods: As many as 323 patients referred to our Thrombosis Ward for a recent (< 6-months) early-onset idiopathic venous thromboembolism (VTE), were compared with 868 gender- and age-matched subjects, in whom a history of venous thrombosis had been excluded, referred during the same period time to our Ward. All had undergone a clinical assessment for smoking habits and for the presence of the components of the metabolic syndrome. Results: The metabolic syndrome was detected in 76/323 cases (23.5%) and in 81/868 controls (9.3%) (p < 0.001; OR:2.990; 95%C.I.:2.119-4.217). Smoking was more common in patients with idiopathic VTE than in controls. In addition to the metabolic syndrome as a whole, its major individual determinants (arterial hypertension, impaired fasting glucose plasma levels, abdominal obesity, hypertriglyceridemia, low HDL-cholesterol) significantly correlated with idiopathic VTE (p always < 0.05). The prevalence of thrombotic events was lower in females than in males (p = 0.000; OR:2.217), the latter being most often hypertensives, smokers, hypertriglyceridemics, carriers of a metabolic syndrome and of impaired fasting glucose than females. In a multivariate analysis, arterial hypertension, impaired fasting glucose, abdominal obesity, and hypercholesterolemia independently predicted idiopathic venous events. Conclusions: Both metabolic syndrome as a whole and its major components individually considered, independently predict early-onset idiopathic VTE.

We describe the scientific motivations, the mission concept and the instrumentation of SPACE, a class-M mission proposed for concept study at the first call of the ESA Cosmic-Vision 2015-2025 planning cycle. SPACE aims to produce the largest three-dimensional evolutionary map of the Universe over the past 10 billion years by taking near-IR spectra and measuring redshifts for more than half a billion galaxies at 0, Comment: 27 pages, Experimental Astronomy, in press. The SPACE team complete list is available at http://urania.bo.astro.it/cimatti/space . The article with full resolution figures is available at http://urania.bo.astro.it/cimatti/space/publications.htm

The assessment and monitoring of liver fibrosis (LF) is a key issue in the management and definition of prognosis of patients with chronic hepatitis C (CHC). In this respect, despite recognized limitations (invasive nature, sampling errors, interobserver variability, nondynamic evaluation of LF), liver biopsy is traditionally considered the reference standard. These limitations stimulated the search for noninvasive approaches for the assessment of LF, particularly attractive in patients with hemophilia and other congenital bleeding disorders (CBD). In patients with congenital bleeding disorders (CBD), who often suffer from CHC because of the past use of nonvirally inactivated plasma-derived products, the risk of bleeding hamper to routinely obtain histological data for LF staging. A variety of methods have been proposed and, in some cases, validated in patients with CHC and other liver diseases, including biomarkers directly or indirectly associated with LF, often combined in scores or algorithms, and the more recently developed physical approaches, evaluating the properties of the liver parenchyma with instrumental techniques studying the propagation of specific signals, that is, transient elastography (TE), acoustic radiation force impulse imaging elastography, and magnetic resonance elastography. This review will describe the available strategies for noninvasive assessment of LF, with more details on the latter promising instrumental approaches. Moreover, although lacking of validation against liver biopsy, recent studies extending the use of noninvasive methods (particularly TE) in the setting of patients with CBD will be discussed.

Injected factor VIII (FVIII), the current treatment for haemophilia A, leads to major improvements in the quality of life and life expectancy of individuals with this disorder. However, because injected FVIII has a short half-life in vivo, this strategy has major limitations for highly demanding regimens (e.g. prophylaxis, immune tolerance induction, surgery). Newer formulations of longer-acting FVIII are presently under investigation. The use of low molecular weight polyethylene glycol (PEG)-containing liposomes as carriers for recombinant FVIII (rFVIII) results in the prolongation of haemostatic efficacy. Data from preclinical experiments in mice, early clinical evaluations, and pharmacokinetics and pharmacodynamics results indicate that an rFVIII pegylated liposomal formulation may provide potential clinical benefit to patients with severe haemophilia A by prolonging the protection from bleeding. In light of this potential clinical benefit, a multicentre, randomized, active-controlled, non-inferiority phase II trial with two parallel treatment arms and equal randomization after stratification for the presence or absence of target joints in patients and for ages >/=18 years vs.

In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding-related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short-term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost-utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health-related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors.

Infantile neuronal ceroid lipofuscinosis (INCL) is a progressive encephalopathy characterized by psychomotor deterioration, early visual loss, and an evanishing EEG. Mutations in the CLN1 gene encoding palmitoyl-protein thioesterase (ppt) have been reported in all Finnish INCL patients and in several non-Finnish North European patients. No cases have been contributed from the Mediterranean area thus far. We identified a single adenine insertion at nucleotide position 169 (A169i) in the CLN1 gene in a family in which the proband suffered from an INCL-like syndrome. The novel mutation was homozygous in blood from the proband, heterozygous in his healthy parents, and not found in control alleles. The mutation leads to an early stop codon resulting in an abnormal and truncatedpptprotein. Our observations provide the first molecular characterization of an Italian INCL patient and expand the list of the known defects in INCL.