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Nissen S.E.,Cleveland Clinic | Stroes E.,University of Amsterdam | Dent-Acosta R.E.,Amgen Inc. | Rosenson R.S.,Mount Sinai School of Medicine | And 63 more authors.
JAMA - Journal of the American Medical Association | Year: 2016

Importance: Muscle-related statin intolerance is reported by 5%to 20%of patients. Objective: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. Design, Setting, and Participants: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. Interventions: Phase A: atorvastatin (20mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420mg monthly) or oral ezetimibe (10mg daily). Main Outcome and Measures: Coprimary end pointswere the mean percent change in LDL-C level from baseline to the mean ofweeks 22 and 24 levels and from baseline toweek 24 levels. Results: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9]mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72]mg/dL). For the mean ofweeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7%(95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5%(95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptomswere reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drugwas stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). Conclusions and Relevance: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety. Copyright © 2016 American Medical Association. All rights reserved.


Marangoni A.,University of Bologna | Nanni C.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi | Quarta C.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi | Foschi C.,University of Bologna | And 8 more authors.
Molecular Imaging and Biology | Year: 2013

Purpose: The aim of this study is to explore the feasibility of 11C-Choline PET in the assessment of the degree of inflammation in the Chlamydia muridarum genital infection model. Procedures: Forty female Balb/c mice received 2.5 mg of medroxyprogesterone acetate i.m. 9 and 2 days prior to the infection: 21 mice were infected by C. muridarum into the vaginal vault, 12 mice were treated with inactivated chlamydiae, and 7 mice were SPG buffer-treated as negative controls. Three healthy control mice were not treated with progesterone. Mice in each category were randomly subdivided in two groups: (1) sacrificed at 5, 10, 15, and 20 days for histological analysis and (2) undergoing 11C-Choline PET at days 5, 10, and 20 post-infection (20 MBq of 11C-Choline, uptake time of 10 min, acquisition through a small-animal PET tomograph for 15 min). Results: Infected animals showed a significantly higher standardized uptake value than both controls and animals inoculated with heat-inactivated chlamydiae in each PET scan (P < 0.05). All organs of the infected animals had scores of inflammation ranging between 2 and 3 at day 5, decreasing to 1-2 at day 20. Conclusions: This preliminary result demonstrated that 11C-Choline PET can highlight a specific proliferation mechanism of inflammatory cells induced by C. muridarum, thanks to a very high sensitivity in detecting very small amounts of tracer in inflammatory cells. © 2013 World Molecular Imaging Society.


Nanni C.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi | Fanti S.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi
PET Clinics | Year: 2010

Sarcomas are a heterogeneous group of tumors that generally present a poor prognosis. Recently, 18F fluorodeoxyglucose (FDG-Positron emission tomography (PET)/computed tomography (CT) was introduced in clinical practice as a possible tool to improve the accuracy of staging these malignant diseases, assess the response to therapy, and as a new prognostic factor. Despite promising results presented in the recent literature, the role of PET imaging is not yet defined in the diagnostic flow chart of sarcomas. This article will describe the results reported in the literature on the use of FDG-PET/CT for the evaluation of patients with sarcoma. A short description of other PET tracers is also added. © 2010 Elsevier Inc. All rights reserved.


Aldini R.,University of Bologna | Micucci M.,University of Bologna | Cevenini M.,University of Bologna | Fato R.,University of Bologna | And 13 more authors.
PLoS ONE | Year: 2014

Phytosterols, besides hypocholesterolemic effect, present anti-inflammatory properties. Little information is available about their efficacy in Inflammatory Bowel Disease (IBD). Therefore, we have evaluated the effect of a mixture of phytosterols on prevention/induction/remission in a murine experimental model of colitis. Phytosterols were administered x os before, during and after colitis induction with Dextran Sodium Sulfate (DSS) in mice. Disease Activity Index (DAI), colon length, histopathology score, 18F-FDG microPET, oxidative stress in the intestinal tissue (ileum and colon) and gallbladder ileum and colon spontaneous and carbachol (CCh) induced motility, plasma lipids and plasma, liver and biliary bile acids (BA) were evaluated. A similar longitudinal study was performed in a DSS colitis control group. Mice treated with DSS developed severe colitis as shown by DAI, colon length, histopathology score, 18F-FDG microPET, oxidative stress. Both spontaneous and induced ileal and colonic motility were severely disturbed. The same was observed with gallbladder. DSS colitis resulted in an increase in plasma cholesterol, and a modification of the BA pattern. Phytosterols feeding did not prevent colitis onset but significantly reduced the severity of the disease and improved clinical and histological remission. It had strong antioxidant effects, almost restored colon, ileal and gallbladder motility. Plasmatic levels of cholesterol were also reduced. DSS induced a modification in the BA pattern consistent with an increase in the intestinal BA deconjugating bacteria, prevented by phytosterols. Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects. Copyright: © 2014 Fonseca et al.


Salvatore V.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi | Borghi A.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi | Peri E.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi | Colecchia A.,Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi | And 9 more authors.
Digestive and Liver Disease | Year: 2012

Aim: We tested the relationship between hepatic haemodynamics assessed by Doppler ultrasonography and liver stiffness assessed by Transient Elastography in hepatitis C related chronic liver disease. Methods: Three liver Doppler ultrasound parameters (hepatic artery resistance index, splenic artery resistance index and waveform pattern in hepatic veins) and liver stiffness measured by Transient Elastography were analysed in one hundred consecutive patients affected by hepatitis C related chronic liver disease. Results: Hepatic and splenic arteries resistance indexes correlate significantly (p< 0.0001 for both) with liver stiffness. A hepatic artery resistance index cut-off value of 0.64 provided sensitivity and specificity respectively of 84.4% and 69.1% for predicting liver stiffness ≤or >13. kPa, whereas a splenic artery resistance index cut-off value of 0.56 provided sensitivity and specificity respectively of 81.3% and 48.5%. The coincidental finding of both resistance indexes above the respective cut-off values showed a good accuracy in identifying patients with liver stiffness values >13. kPa (accuracy = 78%, +LR = 2.90, -LR = 0.31).A significant difference in liver stiffness values was evident between patients with triphasic and bi- or monophasic waveform pattern (p= 0.005). Conclusions: Hepatic and splenic arteries resistance indexes and the hepatic veins waveform pattern assessed by Doppler ultrasound may provide information similar to that of Transient Elastography in hepatitis C related chronic liver disease. © 2011 Editrice Gastroenterologica Italiana S.r.l.


PubMed | Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi
Type: Journal Article | Journal: PET clinics | Year: 2016

Sarcomas are a heterogeneous group of tumors that generally present a poor prognosis. Recently, (18)F fluorodeoxyglucose (FDG-Positron emission tomography (PET)/computed tomography (CT) was introduced in clinical practice as a possible tool to improve the accuracy of staging these malignant diseases, assess the response to therapy, and as a new prognostic factor. Despite promising results presented in the recent literature, the role of PET imaging is not yet defined in the diagnostic flow chart of sarcomas. This article will describe the results reported in the literature on the use of FDG-PET/CT for the evaluation of patients with sarcoma. A short description of other PET tracers is also added.


PubMed | Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi
Type: Comparative Study | Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | Year: 2012

We tested the relationship between hepatic haemodynamics assessed by Doppler ultrasonography and liver stiffness assessed by Transient Elastography in hepatitis C related chronic liver disease.Three liver Doppler ultrasound parameters (hepatic artery resistance index, splenic artery resistance index and waveform pattern in hepatic veins) and liver stiffness measured by Transient Elastography were analysed in one hundred consecutive patients affected by hepatitis C related chronic liver disease.Hepatic and splenic arteries resistance indexes correlate significantly (p<0.0001 for both) with liver stiffness. A hepatic artery resistance index cut-off value of 0.64 provided sensitivity and specificity respectively of 84.4% and 69.1% for predicting liver stiffness or >13 kPa, whereas a splenic artery resistance index cut-off value of 0.56 provided sensitivity and specificity respectively of 81.3% and 48.5%. The coincidental finding of both resistance indexes above the respective cut-off values showed a good accuracy in identifying patients with liver stiffness values >13 kPa (accuracy=78%, +LR=2.90, -LR=0.31). A significant difference in liver stiffness values was evident between patients with triphasic and bi- or monophasic waveform pattern (p=0.005).Hepatic and splenic arteries resistance indexes and the hepatic veins waveform pattern assessed by Doppler ultrasound may provide information similar to that of Transient Elastography in hepatitis C related chronic liver disease.


PubMed | Azienda Ospedaliero Universitaria di Bologna Policlinico sola Malpighi and University of Bologna
Type: Journal Article | Journal: PloS one | Year: 2014

Phytosterols, besides hypocholesterolemic effect, present anti-inflammatory properties. Little information is available about their efficacy in Inflammatory Bowel Disease (IBD). Therefore, we have evaluated the effect of a mixture of phytosterols on prevention/induction/remission in a murine experimental model of colitis. Phytosterols were administered x os before, during and after colitis induction with Dextran Sodium Sulfate (DSS) in mice. Disease Activity Index (DAI), colon length, histopathology score, 18F-FDG microPET, oxidative stress in the intestinal tissue (ileum and colon) and gallbladder ileum and colon spontaneous and carbachol (CCh) induced motility, plasma lipids and plasma, liver and biliary bile acids (BA) were evaluated. A similar longitudinal study was performed in a DSS colitis control group. Mice treated with DSS developed severe colitis as shown by DAI, colon length, histopathology score, 18F-FDG microPET, oxidative stress. Both spontaneous and induced ileal and colonic motility were severely disturbed. The same was observed with gallbladder. DSS colitis resulted in an increase in plasma cholesterol, and a modification of the BA pattern. Phytosterols feeding did not prevent colitis onset but significantly reduced the severity of the disease and improved clinical and histological remission. It had strong antioxidant effects, almost restored colon, ileal and gallbladder motility. Plasmatic levels of cholesterol were also reduced. DSS induced a modification in the BA pattern consistent with an increase in the intestinal BA deconjugating bacteria, prevented by phytosterols. Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects.

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