Chapman R.W.,John Radcliffe Hospital |
Stanghellini V.,S. Orsola Malpighi University Hospital |
Geraint M.,Norgine Ltd |
Halphen M.,Norgine Ltd
American Journal of Gastroenterology | Year: 2013
OBJECTIVES:Polyethylene glycol (PEG) 3350 plus electrolytes (PEG 3350+E) is an established treatment for constipation and has been proposed as a treatment option for constipation associated with irritable bowel syndrome (IBS-C). This study aimed to compare the efficacy and safety of PEG 3350+E vs. placebo in adult patients with IBS-C.METHODS:Following a 14-day run-in period without study medication, patients with confirmed IBS-C were randomized to receive PEG 3350+E (N=68) or placebo (N=71) for 28 days. The primary endpoint was the mean number of spontaneous bowel movements (SBMs) per day in the last treatment week.RESULTS:In both groups, mean weekly number of SBMs (±s.d.) increased from run-in. The difference between the groups in week 4 (PEG 3350+E, 4.40±2.581; placebo, 3.11±1.937) was statistically significant (95% confidence interval: 1.17, 1.95; P<0.0001). Although mean severity score for abdominal discomfort/pain was significantly reduced compared with run-in with PEG 3350+E, there was no difference vs. placebo. Spontaneous complete bowel movements, responder rates, stool consistency, and severity of straining also showed superior improvement in the PEG 3350+E group over placebo in week 4. The most common drug related treatment-emergent adverse events were abdominal pain (PEG 3350+E, 4.5%; placebo, 0%) and diarrhoea (PEG 3350+E, 4.5%; placebo, 4.3%).CONCLUSIONS:In IBS-C, PEG 3350+E was superior to placebo for relief of constipation, and although a statistically significant improvement in abdominal discomfort/pain was observed compared with baseline, there was no associated improvement compared with placebo. PEG 3350+E is a well-established and effective treatment that should be considered suitable for use in IBS-C. © 2013 by the American College of Gastroenterology.
Ambrosini V.,S. Orsola Malpighi University Hospital
Clinical nuclear medicine | Year: 2011
A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.
Mosconi C.,S. Orsola Malpighi University Hospital
British Journal of Cancer | Year: 2016
Background:Intrahepatic cholangiocarcinoma (ICC) is a rapidly progressing malignancy; only a minority of the tumours can be resected and the palliative regimens have shown limited success. The aim of this study was to assess overall survival (OS), tumour response and the safety of radioembolization with yttrium-90 (90Y-TARE) in patients with unresectable/recurrent ICC.Methods:Survival was calculated from the date of the 90Y-TARE procedure. Target and overall Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) and European Association for the Study of the Liver (EASL)—measuring delayed-phase contrast enhancement—treatment responses were assessed at 3 months.Results:The overall median survival was 17.9 months (95% CI: 14.3–21.4 months). Significantly longer survival was obtained in naive patients as compared with patients in whom TARE was preceded by other treatments, including surgery (52 vs 16 months, P=0.009). Significantly prolonged OS was recorded for patients with a response based on mRECIST and the EASL criteria while RECIST responses were not found to be associated with survival. Treatment was well-tolerated, and no mortality was reported within 30 days.Conclusions:In unresectable ICC, 90Y-TARE is safe and offers a survival benefit in naive patients, as well as in responders.British Journal of Cancer (2016) advance online publication 23 June 2016; doi:10.1038/bjc.2016.191 www.bjcancer.com. © 2016 Cancer Research UK
Cosmi B.,S. Orsola Malpighi University Hospital |
Palareti G.,S. Orsola Malpighi University Hospital
Thrombosis Research | Year: 2012
Heparin is an effective, relatively safe, inexpensive parenteral antithrombotic agent widely used in the prevention and treatment of thromboembolic disorders, but it has several limitations such as the marked intra- and inter-patient variability in its anticoagulant response, its poor bioavailability at low doses and its relatively narrow risk to benefit ratio. Low molecular weight heparins (LMWHs), ultra LMWHs and synthetic pentasaccharides have been developed from heparin to overcome its limitations. The characteristics of these compounds are reviewed along with the description of their approved clinical uses. © 2011 Elsevier Ltd. All rights reserved.
Ambrosini V.,S. Orsola Malpighi University Hospital
Clinical nuclear medicine | Year: 2012
A case of Erdheim-Chester disorder, a rare non-Langerhans' cell histiocytosis, was referred for restaging by F-18 FDG PET/CT more than 10 years after initial diagnosis. The patient presented diabetes insipidus, hypergondotropic hypogonadism, and osteosclerotic lesions. Previous bone scintigraphy documented pathognomonic long bones' involvement. Chronic steroid and hormone replacement therapy was administered, and the patient was asymptomatic. F-18 FDG PET/CT was useful for disease restaging at cardiac and soft tissues level.
Renato P.,S. Orsola Malpighi University Hospital
Endocrine | Year: 2015
Metformin is an old insulin sensitizer that has been widely used in women with polycystic ovary syndrome (PCOS) to treat metabolic comorbidities and may also improve ovarian dysfunction in women with PCOS. In fact, metformin may improve insulin resistance, a common finding of PCOS, and reduce insulin blood levels. In this way, androgen production rates can be reduced, and in a subset of women, menses abnormalities and ovulatory rates may improve. The current Endocrine Society Guidelines recommend the use of metformin during adolescence, particularly when excess body weight is present. In the presence of obesity and glucose intolerance states, particularly if those patients fail to modify their lifestyles, metformin may have some significant benefits. Finally, although this drug should not be used as a first-line treatment for ovulatory dysfunctions in adult women with PCOS, there are data supporting the suggestion that in many cases pretreatment with metformin may favor ovulatory response to clomiphene citrate. This article summarizes the available evidence in the favor of metformin use in women with PCOS and emphasizes the need for an individualized therapeutic approach. © 2014, Springer Science+Business Media New York.
Laterza L.,S. Orsola Malpighi University Hospital
Current gastroenterology reports | Year: 2013
Pelvic radiation disease is one of the major complication after radiotherapy for pelvic cancers. The most commonly reported symptom is rectal bleeding which affects patients' quality of life. Therapeutic strategies for rectal bleeding are generally ignored and include medical, endoscopic, and hyperbaric oxygen treatments. Most cases of radiation-induced bleeding are mild and self-limiting, and treatment is normally not indicated. In cases of clinically significant bleeding (i.e. anaemia), medical therapies, including stool softeners, sucralfate enemas, and metronidazole, should be considered as first-line treatment options. In cases of failure, endoscopic therapy, mainly represented by argon plasma coagulation and hyperbaric oxygen treatments, are valid and complementary second-line treatment strategies. Although current treatment options are not always supported by high-quality studies, patients should be reassured that treatment options exist and success is achieved in most cases if the patient is referred to a dedicated centre.
Cosmi B.,S. Orsola Malpighi University Hospital
Journal of Thrombosis and Haemostasis | Year: 2015
Superficial vein thrombosis (SVT) is less well studied than deep vein thrombosis (DVT), because it has been considered to be a minor, self-limiting disease that is easily diagnosed on clinical grounds and that requires only symptomatic relief. The most frequently involved sites of the superficial vein system are the lower limbs, especially the saphenous veins, mostly in relation to varicosities. Lower-limb SVT shares the same risk factors as DVT; it can propagate into the deep veins, and have a complicated course with pulmonary embolism. Clinical diagnosis may not be accurate, and ultrasonography is currently indicated for both confirmation and evaluation of SVT extension. Treatment aims are symptom relief and prevention of venous thromboembolism (VTE) in relation to the thrombotic burden. SVT of the long saphenous vein within 3 cm of the saphenofemoral junction (SFJ) is considered to be equivalent to a DVT, and thus deserving of therapeutic anticoagulation. Less severe forms of lower-limb SVT not involving the SFJ have been included in randomized clinical trials of surgery, compression hosiery, non-steroidal anti-inflammatory drugs, unfractionated heparin, and low molecular weight heparins, with inconclusive results. The largest randomized clinical trial available, on 3004 patients with lower-limb SVT not involving the SFJ, showed that fondaparinux 2.5 mg once daily for 6 weeks is more effective than placebo in reducing the risk of the composite of death from any cause and symptomatic VTE (0.9% versus 5.9%). Further studies are needed to define the optimal management strategies for SVT of the lower limbs and other sites, such as the upper limbs. © 2015 International Society on Thrombosis and Haemostasis.
Cosmi B.,S. Orsola Malpighi University Hospital
Expert Review of Hematology | Year: 2015
Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin (both unfractionated and low-molecular-weight), which is mediated by the formation of IgG antibodies against platelet factor 4-heparin complexes. The IgG/platelet factor 4 immunocomplexes activate platelets with resulting thrombocytopenia, which is not associated with bleeding, but with paradoxical life-threatening thrombotic complications, for coagulation activation. HIT diagnosis requires the assessment of pre-test clinical probability in combination with the measurement of platelet activating antibodies against platelet factor 4-heparin complexes with immunological and functional assays. When HIT is diagnosed, any form of heparin should be stopped and a non-heparin alternative anticoagulant should be started. Argatroban and danaparoid are currently the only drugs licensed for HIT, with different country availability. Bivalirudin is an option in cardiac surgery and procedures in HIT patients. © 2015 Taylor & Francis.
Belosi F.,S. Orsola Malpighi University Hospital
Current radiopharmaceuticals | Year: 2013
68Ga labeled radiopharmaceuticals, like 68Ga-DOATNOC and other similar peptides, are gaining relevance in PET-CT, thanks to relatively easy local generator production, that do not requires an installed cyclotron. However, generator produced 68Ga is typically of suboptimal purity, mainly due to the breakthrough of the parent radionuclide 68Ge. Modern automated synthesis modules adopt both fractionation methods and purification methods in order to get rid of 68Ge breakthrough. Purification methods are mainly based on based on cationic prepurification even if anionic purification has been adopted as well. This work studies the efficacy of cationic prepurification using commercial STRATA-X-C, as well as distribution of the 68Ge contaminant during all steps of the synthesis of labeled peptides. Generator waste, STRATA-X-C purification cartridge, synthesis waste and the final product are quantitatively analyzed by means of high resolution gamma ray spectrometry. Our results show that current method of purification is highly effective; initial 68Ge breakthrough of the order of 1 kBq is decreased by a factor greater than 100, with removal of about 61% of the contaminant 68Ge in the first purification passage; this allow an efficient labeling, since removal of the remaining impurity happens during chelation in the reactor vessel. In conclusion, the synthesis with modular automated system resulted to reliably produce 68Ga-DOTANOC, with limited if any user intervention. 68Ge content in the final formulation results lower than 2x10(-7)%, avoiding unjustified patient irradiation due to radionuclidic impurities and satisfying quality prerequisites for radiopharmaceutical preparations.