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Iagnocco A.,University of Rome La Sapienza | Filippucci E.,Marche Polytechnic University | Sakellariou G.,IRCCS Policlinico San Matteo Foundation | Ceccarelli F.,University of Rome La Sapienza | And 5 more authors.
Clinical and Experimental Rheumatology | Year: 2013

Objective. To investigate the prevalence of shoulder ultrasound (US) detectable abnormalities in asymptomatic individuals of various ages and to correlate the US findings with clinical data. Methods. 97 healthy subjects were enrolled in the present study. They were subgrouped according to their age, as follows: group I (20-29 years); group II (30-39 years); group III (40-49 years); group IV (50-59 years); group V (>60 years). A physical examination of both shoulders, based on a series of provocative maneuvers, was carried out. The US assessment was performed by using a Logiq9 machine equipped with a multi-frequency linear probe working at 12MHz and included the study of a number of structures for the evaluation of local abnormalities, as follows: the long head of biceps tendon (synovial effusion (SE), synovial hypertrophy (SH), power Doppler (PD) signal); the subacromion- subdeltoid and sub-scapularis bursae (SE, SH, PD signal); the rotator cuff tendons (tendinosis, calcifications, tears, impingement); the acromionclavicular (ACJ) and gleno-humeral joints (SE, SH, PD signal, osteophytes, erosions, fibrocartilage calcifications, cartilage abnormalities, tophaceous deposits). In addition, deltoid, throchite and throchine enthesopathy were searched for. Results. 194 shoulders were studied in total. A low but variable percentage of joints of healthy individuals (3.1-13.4%) showed positive provocative maneuvers. 138 shoulders (71.1%) did not show any US abnormalities. The most frequent changes were SE of ACJ (25.5%), osteophytes of ACJ (23.3%), and supraspinatus tendinosis (20.6%). The prevalence of abnormalities progressively increased with age. Sub-clinical involvement was present in most cases, being provocative maneuvers positive only in a low percentage of joints. Conclusion. The present study demonstrated the presence of a wide set of US-detectable changes in healthy subjects, that were more frequently present in elderly individuals. The absence of any clinical sign of local pathology cannot exclude the presence of local abnormalities. © Copyright Clinical and experimental rheumatology 2013.

Harrison C.,Guys and St Thomas NHS Foundation Trust | Kiladjian J.-J.,University Paris Diderot | Al-Ali H.K.,University of Leipzig | Gisslinger H.,Medical University of Vienna | And 10 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Treatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis. METHODS: We assigned 219 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis to receive oral ruxolitinib or the best available therapy. The primary end point and key secondary end point of the study were the percentage of patients with at least a 35% reduction in spleen volume at week 48 and at week 24, respectively, as assessed with the use of magnetic resonance imaging or computed tomography. RESULTS: A total of 28% of the patients in the ruxolitinib group had at least a 35% reduction in spleen volume at week 48, as compared with 0% in the group receiving the best available therapy (P<0.001); the corresponding percentages at week 24 were 32% and 0% (P<0.001). At 48 weeks, the mean palpable spleen length had decreased by 56% with ruxolitinib but had increased by 4% with the best available therapy. The median duration of response with ruxolitinib was not reached, with 80% of patients still having a response at a median follow-up of 12 months. Patients in the ruxolitinib group had an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis. The most common hematologic abnormalities of grade 3 or higher in either group were thrombocytopenia and anemia, which were managed with a dose reduction, interruption of treatment, or transfusion. One patient in each group discontinued treatment owing to thrombocytopenia, and none discontinued owing to anemia. Nonhematologic adverse events were rare and mostly grade 1 or 2. Two cases of acute myeloid leukemia were reported with the best available therapy. CONCLUSIONS: Continuous ruxolitinib therapy, as compared with the best available therapy, was associated with marked and durable reductions in splenomegaly and disease-related symptoms, improvements in role functioning and quality of life, and modest toxic effects. An influence on overall survival has not yet been shown. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT00934544.). Copyright © 2012 Massachusetts Medical Society.

Porcu E.P.,PhD in Experimental Medicine | Salis A.,University of Sassari | Gavini E.,University of Sassari | Rassu G.,University of Sassari | And 2 more authors.
Biotechnology Advances | Year: 2016

Indocyanine green (ICG) is a cyanine compound that displays fluorescent properties in the near infrared region. This dye is employed for numerous indications but nowadays its major application field regards tumour diagnosis and treatments. Optical imaging by near infrared fluorescence provides news opportunities for oncologic surgery. The imaging of ICG can be useful for intraoperative identification of several solid tumours and metastases, and sentinel lymph node detection. In addition, ICG can be used as an agent for the destruction of malignant tissue, by virtue of the production of reactive oxygen species and/or induction of a hyperthermia effect under irradiation. Nevertheless, ICG shows several drawbacks, which limit its clinical application. Several formulative strategies have been studied to overcome these problems. The rationale of the development of ICG containing drug delivery systems is to enhance the in vivo stability and biodistribution profile of this dye, allowing tumour accumulation and resulting in better efficacy. In this review, ICG containing nano-sized carriers are classified based on their chemical composition and structure. In addition to nanosystems, different formulations including hydrogel, microsystems and others loaded with ICG will be illustrated. In particular, this report describes the preparation, in vitro characterization and in vivo application of ICG platforms for cancer imaging and treatment. The promising results of all systems confirm their clinical utility but further studies are required prior to evaluating the formulations in human trials. © 2016 Elsevier Inc.

Monno L.,University of Bari | Annalisa S.,University of Foggia | Scudeller L.,IRCCS Policlinico San Matteo Foundation | Punzi G.,University of Bari | And 5 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

HIV coreceptor tropism (CTR) testing is a prerequisite for prescribing a coreceptor antagonist. CTR is increasingly deduced by analyzing the V3 loop sequence of gp120. We investigated the impact of mutations outside V3 on CTR as determined by the enhanced-sensitivity Trofile assay (ESTA). Paired ESTA and gp120 sequencing (population sequencing; from codon 32 of the conserved C1 to the variable V5 domains) were obtained from 60 antiretroviral treatment (ART)-naïve patients (15 with AIDS) infected with subtype B HIV-1. For gp120 sequence analysis, nucleotide mixtures were considered when the second highest electropherogram peak was >25%; sequences were translated into all possible permutations and classified as X4, dual/mixed (DM), and R5 based on coincident ESTA results. ESTA identified R5 and DM viruses in 72 and 28% of patients, respectively; no pure X4 was labeled. Forty percent of AIDS patients had R5 strains. Thirty-two positions, mostly outside V3, were significantly (P < 0.05) different between R5 and DM sequences. According to multivariate analysis, amino acid changes at 9 and 7 positions within the C1 to C4 and V1 to V5 regions, respectively, maintained a statistical significance, as did the net charge of V3 and C4. When analyzing only R5 sequences, 6 positions in the variable regions were found which, along with the V4 net charge, were significantly different for sequences from early- and end-stage disease patients. This study identifies specific amino acid changes outside V3 which contribute to CTR. Extending the analysis to include pure X4 and increasing the sample size would be desirable to define gp120 variables/changes which should be included in predictive algorithms. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Rossi S.,V Foundation | Ravetta V.,V Foundation | Rosa L.,V Foundation | Ghittoni G.,V Foundation | And 7 more authors.
Hepatology | Year: 2011

In most patients with cirrhosis, successful percutaneous ablation or surgical resection of hepatocellular carcinoma (HCC) is followed by recurrence. Radiofrequency ablation (RFA) has proven effective for treating HCC nodules, but its repeatability in managing recurrences and the impact of this approach on survival has not been evaluated. To this end, we retrospectively analyzed a prospective series of 706 patients with cirrhosis (Child-Pugh class ≤B7) who underwent RFA for 859 HCC ≤35 mm in diameter (1-2 per patient). The results of RFA were classified as complete responses (CRs) or treatment failures. CRs were obtained in 849 nodules (98.8%) and 696 patients (98.5%). During follow-up (median, 29 months), 465 (66.8%) of the 696 patients with CRs experienced a first recurrence at an incidence rate of 41 per 100 person-years (local recurrence 6.2; nonlocal 35). Cumulative incidences of first recurrence at 3 and 5 years were 70.8% and 81.7%, respectively. RFA was repeated in 323 (69.4%) of the 465 patients with first recurrence, restoring disease-free status in 318 (98.4%) cases. Subsequently, RFA was repeated in 147 (65.9%) of the 223 patients who developed a second recurrence after CR of the first, restoring disease-free status in 145 (98.6%) cases. Overall, there were 877 episodes of recurrence (1-8 per patient); 577 (65.8%) of these underwent RFA that achieved CRs in 557 (96.5%) cases. No procedure-related deaths occurred in 1,921 RFA sessions. Estimated 3- and 5-year overall and disease-free (after repeated RFAs) survival rates were 67.0% and 40.1% and 68.0 and 38.0%, respectively. Conclusion: RFA is safe and effective for managing HCC in patients with cirrhosis, and its high repeatability makes it particularly valuable for controlling intrahepatic recurrences. © 2010 American Association for the Study of Liver Diseases.

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