Photodynamic topical antimicrobial therapy for infected foot ulcers in patients with diabetes: A randomized, double-blind, placebo-controlled study - The D.A.N.T.E (Diabetic ulcer Antimicrobial New Topical treatment Evaluation) study
Mannucci E.,Azienda Ospedaliera Universitaria Careggi |
Genovese S.,Instituto Of Ricovero E Cura A Carattere Scientifico Multimedica |
Monami M.,Azienda Ospedaliera Universitaria Careggi |
Navalesi G.,L. Molteni and C |
And 4 more authors.
Acta Diabetologica | Year: 2014
This study was designed to assess the antimicrobial effect and tolerability of a single dose of a photo-activated gel containing RLP068 in the treatment for infected foot ulcers in subjects with diabetes. A randomized, double-blind, parallel series, placebo-controlled phase IIa trial was performed with three concentrations of RLP068 (0.10, 0.30, and 0.50%), measuring total and pathogen microbial load on Day 1 (before and 1 h after topical gel application and photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to systemic treatment with amoxicillin and clavulanic acid. Blood samples were also drawn 1, 2, and 48 h after administration for the assessment of systemic drug absorption. The trial was performed on 62 patients aged ≥18 years, with type 1 or type 2 diabetes and infected foot ulcer, with an area of 2-15 cm 2 and a maximum diameter ≤4.6 cm. A dose-dependent reduction in total microbial load was observed (-1.92 ± 1.21, -2.94 ± 1.60, and -3.00 ± 1.82 LogCFU/ml for 0.10, 0.30, and 0.50% RPL068 vs. -1.00 ± 1.02 LogCFU/ml with placebo) immediately after illumination, with a progressive fading of the effect during follow-up. No safety issues emerged from the analysis of adverse events. Systemic absorption of RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of infected diabetic foot ulcers is well tolerated and produces a significant reduction in germ load. Further clinical trials are needed to verify the efficacy of this approach as add-on to systemic antibiotic treatment. © Springer-Verlag 2013.
Della Porta M.G.,Fondazione IRCCS Policlinico San Matteo |
Della Porta M.G.,University of Pavia |
Alessandrino E.P.,Fondazione IRCCS Policlinico San Matteo |
Bacigalupo A.,San Martino Hospital |
And 19 more authors.
Blood | Year: 2014
Approximately one-third of patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (HSCT) are cured by this treatment. Treatment failure maybe due to transplant complications or relapse. To identify predictive factors for transplantation outcome, we studied 519 patients with MDS or oligoblastic acute myeloid leukemia (AML, <30%marrow blasts) who received an allogeneic HSCT and were reported to the Gruppo Italiano Trapianto di Midollo Osseo registry between 2000 and 2011. Univariate and multivariate survival analyses were performed using Cox proportional hazards regression. High-risk category, as defined by the revised International Prognostic Scoring System (IPSS-R), and monosomal karyotype were independently associated with relapse and lower overall survival after transplantation. On the other hand, older recipient age and high hematopoietic cell transplantation-comorbidity index (HCT-CI) were independent predictors of nonrelapse mortality. Accounting for various combinations of patient's age, IPSS-R category, monosomal karyotype, and HCT-CI, the 5-year probability of survival after allogeneic HSCT ranged from 0% to 94%. This study indicates that IPSS-R risk category and monosomal karyotype are important factors predicting transplantation failure both in MDS and oligoblastic AML. In addition, it reinforces the concept that allogeneic HSCT offers optimal eradication of myelodysplastic hematopoiesis when the procedure is performed before MDS patients progress to advanced disease stages. © 2014 by The American Society of Hematology.
Park J.-W.,Asklepios Klinik Harburg |
Bethencourt A.,Hospital Universitario Son Dureta |
Sievert H.,Cardiovascular Center Sankt Katharinen |
Santoro G.,Azienda Ospedaliera Universitaria Careggi |
And 7 more authors.
Catheterization and Cardiovascular Interventions | Year: 2011
Background: In most patients with atrial fibrillation (AF) and stroke, there is thrombotic embolization from the left atrial appendage (LAA). Percutaneous closure of the LAA is a novel alternative for the treatment of patients with AF at a high risk of stroke, in whom long-term anticoagulation therapy is not possible or not desired. This study details the initial experience with the Amplatzer Cardiac Plug (ACP) in humans. Methods: Investigator-initiated retrospective preregistry data collection to evaluate procedural feasibility and safety up to 24 hr after implantation of the ACP, a nitinol device designed for percutaneous trans-septal implantation in LAA of patients with paroxysmal, permanent, or persistent AF. Results: In 137 of 143 patients, LAA occlusion was attempted, and successfully performed in 132 (96%). There were serious complications in 10 (7.0%) patients (three patients with ischemic stroke; two patients experienced device embolization, both percutaneously recaptured; and five patients with clinically significant pericardial effusions). Minor complications were insignificant pericardial effusions in four, transient myocardial ischemia in two, and loss of the implant in the venous system in one patient. Conclusion: The implantation of the ACP device is a feasible method for percutaneous occlusion of the LAA. © 2011 Wiley-Liss, Inc.
Rotellini M.,University of Florence |
Paglierani M.,Azienda Ospedaliera Universitaria Careggi |
Pepi M.,University of Florence |
Franchi A.,University of Florence
Journal of Oral Pathology and Medicine | Year: 2012
Background: Warthin's tumour (WT) is a common benign lesion of the major salivary glands. The nature of WT remains controversial, with particular regard to the presence of clonal chromosomal abnormalities, including the t(11;19) translocation involving the CRTC1 and MAML2 genes, that have been identified in both WT and mucoepidermoid carcinoma. In this study, we focused our attention on metaplastic WT variants, and we conducted a fluorescent in situ hybridisation (FISH) analysis for the presence of MAML2 gene rearrangement. Methods: Dual-colour FISH analysis was performed on paraffin-embedded sections of eight WTs showing metaplastic changes (five with squamous metaplasia, two with mucinous metaplasia and one with both) using a MAML2 break-apart probe. Results: Presence of split signals indicative of gene rearrangement was identified in a subset of cells in areas of squamous metaplasia in two samples of WT. No rearrangement was observed in the oncocytic epithelium, in lymphocytes and in areas of mucinous metaplasia. Conclusions: The presence of a small subpopulation of cells carrying MAML2 rearrangement in areas of squamous metaplasia within WT could predispose these lesions to malignant transformation in mucoepidermoid carcinoma and could represent a molecular link between the two entities. © 2012 John Wiley & Sons A/S.
Franchi A.,University of Florence |
Baroni G.,University of Florence |
Sardi I.,Azienda Ospedaliera Universitaria Meyer |
Giunti L.,Azienda Ospedaliera Universitaria Meyer |
And 2 more authors.
Virchows Archiv | Year: 2012
Peripheral dedifferentiated chondrosarcoma (DCS) is an exceedingly rare aggressive surface bone neoplasm in which a high-grade sarcoma arises within an osteochondroma. Four such examples were identified in our files, representing 11.1% of all DCS treated at our hospital in the years 1995-2010, and were the object of thepresentstudy.Thepatientsweretwomenandtwo women ranging in age between 30 and 64 years, with tumors located in the pelvis (n = 2), in the scapula (n = 1), and the tibia (n = 1). Radiologically, there was evidence of a preexisting osteochondroma associated with aggressive osteolytic areas at the base and periphery of the exostosis, extending to the bone segment of origin and to the soft tissues. Immunohistochemical analysis of cell cycle regulators showed consistent loss in the expression of p16 and overexpression of cyclin D1, and to a lesser extent of RB and p53, in the anaplastic compartments of peripheral DCS in comparison with the well-differentiated cartilaginous components, while no significant expression of MDM2 was observed in any of the cases studied. Moreover, PDGFRα was absent in both tumor components, and PDGF-Rβ was strongly and diffusely positive in all the cases. Finally, no mutations were identified in exons 4-9 of the TP53 gene in both cases, showing positivity for p53 in the anaplastic component. In conclusion, our study shows that alterations of genes implicated in the regulation of the G1 to the S phase cell cycle checkpoint contribute to the process of dedifferentiation in peripheral secondary chondrosarcoma (CS), although the molecular mechanisms seem at least in part to differ from those involved in the process of dedifferentiation of central CS. PDGFRβ could represent a potential target for treatments with receptor tyrosine kinase inhibitors in peripheral DCS. © 2012 Springer-Verlag.
Santoro R.,University of Florence |
Meccariello G.,University of Florence |
Mannelli G.,University of Florence |
Bini B.,University of Florence |
And 2 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2014
After failure of curative radiotherapy (RT), surgery is the main therapeutic option to control recurrent laryngeal cancer. Recurrences after RT for T1-T2 tumours of the glottic larynx are often diagnosed at a more severe stage than the original disease and, thus, usually treated by radical approaches. Our aim is to investigate the feasibility of more conservative strategies for proper treatment of post-RT recurred glottic cancer. We collected and reviewed our files from 1990 to 2006, selecting 75 patients which matched the following inclusion criteria: (1) patient was originally diagnosed with early stage squamous cell carcinoma of the glottic larynx (stage I-II according to 2010 TNM), (2) patient was treated by RT with curative intent, (3) patient presented a recurrence of disease after RT which was surgically treated at our Institution. T stage at first diagnosis was T1a in 41 cases (55 %), T1b in 12 (16 %) and T2 in 22 (29 %). At clinical examination of RT-recurred lesions, we documented advanced lesions (rT3-rT4) in 29 out of 75 patients (39 %). Overall, an upstage was reported for 56 % RT-recurred cancers, while 37.3 % remained at the same stage than the original tumour and 6.7 % were downstaged. Twelve patients (16 %) underwent salvage partial laryngectomy (SPL), while 63 (84 %) received a salvage total laryngectomy (STL). Multivariate analysis showed that rTNM according to the AJCC-UICC of 2010 was the only prognostic factor for both disease-free survival (p = 0.042) and overall survival (p = 0.004). Considering the prognostic impact of rT and rN we documented a statistical significance only in terms of overall survival for both factors (p = 0.004 and p = 0.04, respectively). Although STL remains the most frequent treatment choice for failures after RT in laryngeal carcinomas, SPL represents a valid option for selected patients with limited recurrence and can deliver good oncologic and functional results if performed according to careful indications. © 2013 Springer-Verlag.
Franchi A.,University of Florence |
Palomba A.,Azienda Ospedaliera Universitaria Careggi |
Cardesa A.,University of Barcelona
Histopathology | Year: 2011
Several malignant tumours occurring in the sinonasal tract may present with an undifferentiated morphology. Overall, these lesions pose significant diagnostic difficulties for the surgical pathologist, especially in limited biopsy material, but their correct classification is becoming increasingly important for an appropriate treatment strategy. This review deals with the criteria for differential diagnosis of these neoplasms, with emphasis on recent advances in immunohistochemistry and molecular biology, as well as with previous progress in electron microscopy. Through careful microscopic examination of haematoxylin and eosin-stained sections, in the light of clinical information and imaging data, a list of differential diagnoses can be made and an appropriate panel of antibodies can be chosen to further categorize the tumour. An initial panel including cytokeratins, synaptophysin, S100 protein, desmin and CD45 may allow the classification of most lesions or may help to narrow the list of differential diagnoses. Further refinement can be obtained through second-line markers, including in-situ hybridization for Epstein-Barr virus, other neuroendocrine markers, melanocytic markers, myogenin, CD99, other lymphocyte markers, and CD138 and light chains. Finally, molecular analysis can further assist in the recognition of specific entities such as nuclear protein in testis midline carcinoma, Ewing's sarcoma/peripheral neuroectodermal tumour, alveolar rhadbomyosarcoma, and poorly differentiated synovial sarcoma. © 2011 Blackwell Publishing Limited.
Galli M.,Div. of Hematology |
Salmoiraghi S.,Div. of Hematology |
Golay J.,Div. of Hematology |
Gozzini A.,Azienda Ospedaliera Universitaria Careggi |
And 3 more authors.
Annals of Hematology | Year: 2010
ITF2357, an orally effective member of the family of histone deacetylase inhibitors, is a potent inducer of apoptosis and death of multiple myeloma (MM) cells. We performed a phase-II, multiple-dose clinical trial in 19 patients with relapsed or progressive MM to determine the maximum tolerated dose (MTD) of ITF2357 administered twice daily for four consecutive days every week for 4 weeks (i.e., first cycle). The first six patients received 150 mg ITF2357 twice daily. Since two of them experienced a dose-limiting toxicity (DLT) during the first cycle, the subsequent patients received 100 mg ITF2357 twice daily. This was the MTD, as only one DLT occurred. Up to 12 weeks (i.e., three cycles) of treatment were scheduled. Oral dexamethasone was allowed to a maximum weekly amount of 20 mg. Median duration of treatment was 6 weeks, ranging from two (two patients) to 12 weeks (five patients). Four patients suffered from serious adverse events. Three patients experienced grade 3-4 gastro-intestinal toxicity and three had transient electrocardiographic abnormalities. Thrombocytopenia occurred in all but one patient (grade 3-4 in ten patients). At last followup, five patients were in stable disease, five had disease progression, and nine had died all of progressive MM. In conclusion, when given at a dose of 100 mg twice daily alone or combined with dexamethasone, ITF2357 proved tolerable but showed a modest clinical benefit in advanced MM. © Springer-Verlag 2009.
Berti S.,Ospedale Del Cuore |
Paradossi U.,Ospedale Del Cuore |
Meucci F.,Azienda Ospedaliera Universitaria Careggi |
Trianni G.,Ospedale Del Cuore |
And 6 more authors.
JACC: Cardiovascular Interventions | Year: 2014
Methods ICE-guided percutaneous LAA closure was performed in 121 patients to evaluate the following tasks typically achieved by TEE: assessment of the LAA dimension for device sizing; guidance of transseptal puncture; verification of the delivery sheath position; confirmation of location and stability of the device before and after release and continuous monitoring to detect procedural complications. In 51 consecutive patients, we compared the measurements obtained by ICE and fluoroscopy to choose the size of the device.Results The device was successfully implanted in 117 patients, yielding a technical success rate of 96.7%. Procedural success was achieved in 113 cases (93.4%). Four major adverse events (3 cardiac tamponades and 1 in-hospital transient ischemic attack) occurred. There was significant correlation in the measurements for device sizing assessed by angiography and ICE (r = 0.94, p < 0.0001).Conclusions ICE imaging was able to perform the tasks typically provided by TEE during implantation of the Amplatzer Cardiac Plug device for LAA occlusion. Therefore, we provide evidence that the use of ICE offered accurate measurements of LAA dimension in order to select the correct device sizes.Objectives This dual-center study sought to demonstrate the utility and safety of intracardiac echocardiography (ICE) in providing adequate imaging guidance as an alternative to transesophageal echocardiography (TEE) during Amplatzer Cardiac Plug device implantation.Background Over 90% of intracardiac thrombi in atrial fibrillation originate from the left atrial appendage (LAA). Patients with contraindications to anticoagulation are potential candidates for LAA percutaneous occlusion. TEE is typically used to guide implantation. © 2014 American College of Cardiology Foundation.
Rigacci L.,Azienda Ospedaliera Universitaria Careggi
Annals of Hematology | Year: 2012
Patients who relapse after an autologous hematopoietic stem cell transplantation (SCT) have a very poor prognosis. We have retrospectively analyzed diffuse large B cell lymphoma patients who underwent an allo-SCT after an auto-SCT relapse reported in the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) database. From 1995 to 2008, 3449 autologous transplants were reported in the GITMO database. Eight hundred eighty-four patients relapsed or progressed after transplant; 165 patients, 19% of the relapsed patients, were treated with allo-transplant. The stem cell donor was related to the patient in 108 cases. A reduced intensity conditioning regimen was used in 116. After allo-SCT, 72 patients (43%) obtained a complete response and 9 obtained a partial response with an overall response rate of 49%; 84 patients (51%) experienced rapid progression of disease. Ninety-one patients died, 45 due to disease and 46 due to treatment-related mortality. Acute graft-versus-host disease was recorded in 57 patients and a chronic GvHD in 38 patients. With a median follow-up of 24 months (2-144) after allo, overall survival (OS) was 39%, and after a median of 21 months (2-138) after allo, progression-free survival (PFS) was 32%. Multivariate analysis indicated that the only factors affecting OS were status at allo-SCT, and those affecting PFS were status at allo-SCT and stem cell donor. This retrospective analysis shows that about onefifth of patients with diffuse large B cell lymphoma who experience relapse after autologous transplantation may be treated with allogeneic transplantation. Moreover, the only parameter affecting either OS or PFS was the response status at the time of allo-SCT. © Springer-Verlag 2012.