Naldi L.,Azienda Ospedaliera Papa Giovanni XXIII |
Naldi L.,Centro Studi
British Journal of Dermatology | Year: 2016
Intangible and institutional conflicts of interest can particularly affect academia. Academic scientists have peculiar social responsibilities with respect to education and research. These responsibilities may conflict with the increased presence of industry in academia and commercialization of academic research through patents and royalties. Drug approval is almost entirely dependent worldwide on data produced in studies led by pharmaceutical industries. A reflection of the increasing role of the market in academic research is given by exaggerated claims in press releases by academic institutions. In consideration of the extensive presence of industry in academia, there is a need for a move from individual to institutional conflicts of interest disclosure, defining institutional policies for regulating conflicts of interest and developing an 'ethically credible partnership'. © 2016 British Association of Dermatologists.
Shimamura K.,Azienda Ospedaliera Papa Giovanni XXIII |
Guagliumi G.,Azienda Ospedaliera Papa Giovanni XXIII
Circulation Journal | Year: 2016
Decision making on lesion preparation and stent/scaffold optimization are cornerstones of patient outcome. Intravascular imaging recently emerged as a critical modality to achieve better results of stent/scaffold implantation and superior clinical outcomes compared with coronary angiography alone. Optical coherence tomography (OCT), a light-based intravascular imaging modality with high frame rate in acquisition and very high speed pullback, can interrogate the target vessel in a couple of seconds, and immediately display a pristine longitudinal lumen contour with automatic detection of lesion severity, site and lumen/stent areas. Further, OCT provides pivotal information on sites of calcium, with accurate measurements of the minimum distance from the lumen, a major determinant of stent/ scaffold underexpansion, malapposition and eccentricity. Finally, to guide the PCI procedure using OCT without operator misjudgment, a real-time point-to-point correspondence between angiographic and OCT images has been recently created. Co-registration of OCT with angiography with direct tableside control of acquisition and analysis enables the operator to plan and map optimal stent/scaffold implantation. To prove the clinical relevance of OCT-guided PCI, simple, standardized interventional planning, including pre- and postprocedural automatic lumen detection metrics, has to be translated into effective treatment flow algorithms. A similar OCT algorithm is being tested in the ongoing prospective, randomized, multicenter ILUMIEN III study, to demonstrate that OCT-guided stent placement is superior to angiography-guided and non-inferior to IVUS-guided stent implantation. © 2016, Japanese Circulation Society. All rights reserved.
Colledan M.,Azienda Ospedaliera Papa Giovanni XXIII |
Zanfi C.,S Orsola Hospital |
Pinna A.D.,S Orsola Hospital
Current Opinion in Organ Transplantation | Year: 2013
Purpose of review: Intestinal transplantation includes an heterogeneous group of procedures in which different compositions of organs are transplanted. The current classification includes four groups according to the inclusion of the liver and/or the stomach in the graft: isolated intestinal transplantation, liver-intestinal transplantation, multivisceral transplantation, and modified multivisceral transplantation. Variants exist, the technical evolution having been slow, yet constant over years. Recent findings: The most relevant early technical improvements were aimed at achieving better feasibility and safety of the most difficult aspects of the different procedures, such as removal of the recipient's diseased organs, performing of vascular reconstructions and prevention of complications as with retention of the donor's duodenum and pancreas in liver-intestine transplantation. More recently, apart from a clear definition of the classification of the procedures, progress has been more directed in a conservative direction such as the preservation of the native spleen with and without the pancreas in multivisceral transplants. Summary: After achieving consistent satisfactory short-term results, the technical interest in intestinal transplantation is now moved to solutions that, in spite of a possible increased difficulty, may offer better opportunities of mid-term and long-term successes, both in terms of survival and quality of life. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Gyulai R.,University of Szeged |
Gyulai R.,University of Pécs |
Bagot M.,Saint Louis Hospital |
Griffiths C.E.M.,University of Manchester |
And 5 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015
Background: Methotrexate is one the most commonly used systemic therapies for psoriasis. Despite its widespread use in psoriasis therapy, dermatologists' practice regarding the use of methotrexate has not been investigated on global scale. Objective: To evaluate the real life use of methotrexate for psoriasis treatment in the dermatological community worldwide. Methods: A questionnaire consisting of 41 questions was designed by the Psoriasis International Network (PIN). Questions focused on safety, dosing, administration, folic acid supplementation and combination therapy aspects of methotrexate use. The anonymous web-based survey was distributed to dermatologists by the national coordinators of PIN. Results: Between 2 April and 7 August 2012, 481 dermatologists from 63 countries completed the questionnaire. Most respondents were from European and South American countries, whereas the response rate from Central America and the Near East was lowest. The majority of responders were experienced dermatologists (86% had more than 5 years of experience in psoriasis treatment). Starting and maintenance doses of 10 mg of methotrexate or lower were reported by 67% and 42% of respondents respectively. Thirty-eight per cent of respondents stop treatment at a cumulative dose of 2 g, whereas 36% did not consider cumulative dose important in this respect. The primary mode of administration was oral, and the majority of respondents administer folic acid supplementation. Almost all respondents monitored full blood count, liver and renal function tests, whereas procollagen 3 amino terminal peptide measurement and transient elastography is used by only a minority of dermatologists. There were significant differences concerning the doses, routes of administration and safety monitoring among the clinical practices in different geographical locations. Conclusion: Current clinical practice of methotrexate use in psoriasis is not uniform, depends on geographical location, and is not in full agreement with clinical guidelines. © 2014 European Academy of Dermatology and Venereology.
Naldi L.,Azienda Ospedaliera Papa Giovanni XXIII |
Naldi L.,Centro Studi GISED |
Crotti S.,Centro Studi GISED
Giornale Italiano di Dermatologia e Venereologia | Year: 2014
Cutaneous reactions represent in many surveillance systems, the most frequent adverse events attributable to drugs. The spectrum of clinical manifestations is wide and virtually encompasses any known dermatological disease. The introduction of biological agents and so-called targeted therapies has further enlarged the number of reaction patterns especially linked with cytokine release or inbalance. The frequency and clinical patterns of cutaneous reactions are influenced by drug use, prevalence of specific conditions (e.g., HIV infection) and pharmacogenetic traits of a population, and they may vary greatly among the different populations around the world. Studies of reaction rates in cohorts of hospitalized patients revealed incidence rates ranging from, 1 out 1000 to 2 out 100 of all hospitalized patients. For drugs such as aminopenicillines and sulfamides the incidence of skin reactions is in the order of 3-5 cases out of 100 exposed people. Although the majority of cutaneous reactions are mild and self-limiting, there are reactions such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) which are associated with significant morbidity and mortality. Surveillance systems routed on sound epidemiologic methodology, are needed to raise signals and to assess risks associated with specific reactions and drug exposures. Identification of risk factors for adverse reactions and appropriate genetic screening of groups at higher risk may improve the outcomes of skin reactions.
Hay R.J.,International Foundation for Dermatology |
Johns N.E.,University of Washington |
Williams H.C.,University of Nottingham |
Bolliger I.W.,University of Washington |
And 9 more authors.
Journal of Investigative Dermatology | Year: 2014
The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency. © 2014 The Society for Investigative Dermatology.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.4-3 | Award Amount: 9.64M | Year: 2012
Chronic kidney disease (CKD) affects 8% of the European population and ultimately results in renal failure due to progressive fibrosis. CDK carries a high mortality risk and the number of affected people rises, increasing the demand on renal replacement therapies while the number of available donor organs stays stable. The STELLAR consortium proposes to develop an alternative to renal replacement therapy, based on the repair capacity of newly discovered kidney mesenchymal stromal cells (kMSCs). By injecting kMSC into affected kidneys, we expect to stop kidney fibrosis and induce tissue repair, ultimately leading to the restoration of normal kidney function. The STELLAR consortium will develop protocols for up scalable, high quality isolation of kMSCs and precisely characterize kMSC function in comparison to other MSCs. test kMSCs in several murine renal disease models, to study their effects on fibrosis and tissue repair. discover mechanisms of kidney repair. invest in developing the technology necessary for up scaled isolation and quality control. The STELLAR consortium combines Australian experts on kMSC isolation and characterisation with European experts on renal failure and compounds the state-of-the-art knowledge, facilities and experience needed to develop and validate this novel form of renal therapy. The inclusion of experienced SMEs, with great technical and scientific know-how about assay and protocol development, further strengthens the consortium and will ensure not only the inclusion of new technology, but also a quick translation from bench to clinical application. In conclusion, the STELLAR consortium is capable of developing and pre clinical validation of this new cellular therapy for CDK, based on a new understanding of stromal cells and fibroblast function, while also providing the technology required for rapid, large scale application of the therapy after clinical validation.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.2-1 | Award Amount: 7.98M | Year: 2010
According to the European Society of Cardiology there has been an increase in the life expectancy at the age of 65 of the European population from 15.0 to 17.0 years in the years since 1980. In the elderly, up to 50% of deaths are caused by cardiovascular diseases, the majority accounted for by coronary artery disease. The most effective treatment for obstructive coronary disease is percutaneous intervention with coronary stenting and fuelled by the increasing disease burden there has been a rapid increase in the number of percutaneous coronary intervention procedures in Europe from 184,000 in 1992 to 885,000 in 2004. If the rate of progression remains constant, the projected number of coronary intervention procedures per annum will be about 1.5 million by 2010, with a stenting rate of close to 100%. The principal safety issue with current coronary stenting procedures is late stent thrombosis which, with a case mortality rate approaching 50%, makes this problem a very significant European health issue. The PRESTIGE project will result in significant improvement in prediction and prevention of late stent thrombosis by providing novel strategies that causally impede incident events without increasing the overall risk of bleeding. These goals will be achieved by a multidisciplinary consortium formed by world-leading EU-based specialists covering the requisite scientific skills and experience. Since the first drug-eluting stent was introduced in 2002 the growth of this sector has been explosive. Forecasts predicted the potential for this market segment to exceed 4.6 billion by 2009. The economic impact of this very ambitious project will be to provide the European health industries with novel stent products and new imaging technologies to identify patients at-risk, as well as amended European treatment guidelines. The social impact will be, amongst others, a tremendous cost reduction for the public and private health insurance systems all over Europe.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 5.99M | Year: 2015
Type 2 diabetes will affect >500 million adults by 2040 and its secondary complications will generate enormous socioeconomic costs - in particular, diabetic kidney disease (DKD), which is already the most common cause of chronic kidney disease. DKD is associated with greatly increased mortality and frequently progresses to end stage renal failure. Pharmacotherapy, dialysis and transplantation represent the mainstay treatments for DKD but are costly and provide only limited protection against adverse outcomes. Mesenchymal Stromal Cell (MSC) therapy is a promising approach to halting the progression of DKD toward end-stage renal failure and may also have ancillary benefits in Type 2 diabetes. In preliminary research, we have demonstrated that a single dose of MSC simultaneously improves kidney function (glomerular filtration rate and albuminuria) as well as hyperglycaemia in animals with DKD. NEPHSTROM will conduct a multi-centre, placebo-controlled clinical trial of a novel MSC therapy for stabilization of progressive DKD, leading to superior clinical outcomes and long-term socioeconomic benefit. A key enabler for this trial is a novel MSC population (CD362\MSC, trade name ORBCEL-M) which delivers higher purity and improved characterisation compared to conventional plastic-adherent MSC. The NEPHSTROM Phase 1b/2a clinical trial will investigate the safety, tolerability and preliminary efficacy of a single intravenous infusion of allogeneic ORBCEL-M versus placebo in adults with progressive DKD. NEPHSTROM investigators will also determine the bio-distribution, mechanisms of action, immunological effects and economic impacts associated with ORBCEL-M therapy for DKD. This research will critically inform the optimal design of subsequent Phase 3 trials of ORBCEL-M. Stabilising progressive DKD through NEPHSTROMs next-generation MSC therapy will reduce the high all-cause mortality and end-stage renal failure risk in people with this chronic non-communicable disease
BETA3_LVH - A multi-center randomized, placebo-controlled trial of mirabegron, a new beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 5.43M | Year: 2015
Patients with cardiovascular risk factors, e.g. hypertension and obesity are at risk of developing heart failure with preserved ejection fraction (HFpEF), a highly prevalent disease in the elderly, mostly women population. There is currently no specific, defined treatment for HFpEF, beyond control of risk factors. Activation of cardiac and vascular Beta3-adrenergic receptors (B3AR) represents a new concept and a novel target for structural cardiac disease. B3AR expression and coupling were demonstrated in human myocardium and vasculature. In pre-clinical models with expression of the human receptor, its activation attenuates myocardial remodelling, i.e. decreases hypertrophy and fibrosis in response to neurohormonal or hemodynamic stress. Mirabegron is a new agonist of B3AR available for human use, that was recently introduced for a non-cardiovascular indication (overactive bladder disease). The primary objective of the project is to design and implement a multi-centric, prospective, randomized, placebo-controlled clinical trial testing the additional beneficial effect of mirabegron, versus placebo over 12 months on top of standard treatment of patients carrying structural cardiac disease without overt heart failure (stage B of AHA classification); the co-primary end-point will be the quantitative change in myocardial hypertrophy measured by cardiac MRI; and in diastolic ventricular function, measured by Doppler echocardiography (E/E); in addition, exercise tolerance (peak VO2) will be measured as well as circulating biomarkers reflecting both myocardial remodeling and function. In addition, we will test the effect of mirabegron on beige/brown fat activation and metabolism. Our proposal therefore combines a major conceptual advance and repurposing of an original drug to validate pre-clinical discoveries in the context of a major health problem.