Moonen A.,Catholic University of Leuven |
Annese V.,AOU Careggi |
Belmans A.,Interuniversity Center for Biostatistics and Statistical Bioinformatics |
Varannes S.B.D.,University of Nantes |
And 9 more authors.
Gut | Year: 2016
Objective: Achalasia is a chronic motility disorder of the oesophagus for which laparoscopic Heller myotomy (LHM) and endoscopic pneumodilation (PD) are the most commonly used treatments. However, prospective data comparing their long-term efficacy is lacking. Design:201 newly diagnosed patients with Achalasia were randomly assigned to PD (n=96) or LHM (n=105). Before randomisation, symptoms were assessed using the Eckardt score, functional test were performed and quality of life was assessed. The primary outcome was therapeutic success (presence of Eckardt score =3) at the yearly follow-up assessment. The secondary outcomes included the need for re-treatment, lower oesophageal sphincter pressure, oesophageal emptying and the rate of complications. Results: In the full analysis set, there was no significant difference in success rate between the two treatments with 84% and 82% success after 5 years for LHM and PD, respectively (p=0.92, log-rank test). Similar results were obtained in the per-protocol analysis (5-year success rates: 82% for LHM vs 91% for PD, p=0.08, log-rank test). After 5 years, no differences in secondary outcome parameter were observed. Redilation was performed in 24 (25%) of PD patients. Five oesophageal perforations occurred during PD (5%) while 12 mucosal tears (11%) occurred during LHM. Conclusions: After at least 5 years of follow-up, PD and LHM have a comparable success rate with no differences in oesophageal function and emptying. However, 25% of PD patients require redilation during follow-up. Based on these data, we conclude that either treatment can be proposed as initial treatment for Achalasia. Trial registration numbers Netherlands trial register (NTR37) and Current Controlled Trials registry (ISRCTN56304564).
Poli D.,AOU Careggi |
Antonucci E.,AOU Careggi |
Testa S.,Haemostasis and Thrombosis Center |
Tosetto A.,S Bortolo Hospital |
And 2 more authors.
Circulation | Year: 2011
Background-: Vitamin K antagonist (VKA) therapy is increasingly being used for the prevention of venous thromboembolism and stroke in atrial fibrillation. Bleeds are the major concern for VKA prescription, especially in very old patients who carry many risk factors for bleeding. We performed a large multicenter prospective observational study that enrolled very old patients to evaluate the quality of anticoagulation and the incidence of bleedings. Methods and results-: The study included 4093 patients 80 years of age who were naïve to VKA for thromboprophylaxis of atrial fibrillation or after venous thromboembolism. Patients demographic and clinical data were collected, and the quality of anticoagulation and the incidence of bleeding were recorded. The follow-up was 9603 patient-years; median age at the beginning of follow-up was 84 years (range, 80 to 102 years). We recorded 179 major bleedings (rate, 1.87 per 100 patient-years), 26 fatal (rate, 0.27 per 100 patient-years). The rate of bleeding was higher in men compared with women (relative risk, 1.4; 95% confidence interval, 1.12 to 1.72; P=0.002) and among patients 85 years of age compared with younger patients (relative risk, 1.3; 95% confidence interval, 1.0 to 1.65; P=0.048). Time in therapeutic range was 62% (interquartile range, 49% to 75%). History of bleeding, active cancer, and history of falls were independently associated with bleeding risk in Cox regression analysis. Conclusion-: In this large study on very old patients on VKA carefully monitored by anticoagulation clinics, the rate of bleedings was low, suggesting that age in itself should not be considered a contraindication to treatment. Adequate management of VKA therapy in specifically trained center allows very old and frail patients to benefit from VKA thromboprophylaxis. © 2011 American Heart Association. All rights reserved.
Poli D.,AOU Careggi |
Antonucci E.,University of Florence |
Zanazzi M.,Renal Unit |
Grifoni E.,University of Florence |
And 3 more authors.
Thrombosis and Haemostasis | Year: 2012
Vitamin K antagonists (VKA) therapy is increasingly used in elderly for prevention of venous thromboembolism (VTE) and of stroke in atrial fibrillation (AF). Glomerular filtration rate (GFR), usually estimated from different equations, decreases progressively with age and it is a risk factor for bleeding. In the frame of the EPICA study, a multicentre prospective observational study including 4,093 patients ≥80 years naïve to VKA treated for AF or after VTE, we performed this ancillary study to evaluate the prevalence of chronic kidney diseases (CKD) by estimated GFR (eGFR). Incidence of bleedings was recorded and bleeding risk was evaluated in relation to eGFR calculated by Cockroft-Gault (C-G); Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. In addition, the agreement among the three eGFR formulas was evaluated. We recorded 179 major bleedings (rate 1.87 x100 patient-years [py]), 26 fatal (rate 0.27 x100 py). Moderate CKD was detected in 69.3%, 59.3% and 47.0% and severe CKD in 5.8%, 7.4% and 10.0% of cases by C-G, MDRD and CKD-EPI, respectively. Bleeding risk was higher in patients with severe CKD irrespective of the applied equation. This study confirms that CKD represents an independent risk factor for bleeding and that a wide proportion of elderly on VKA had severe or moderate CKD, suggesting the need for frequent monitoring. Although the different available equations yield different eGFR, all appear to similarly predict the risk of major bleeding. © Schattauer 2012.
Soverini S.,University of Bologna |
De Benedittis C.,University of Bologna |
Papayannidis C.,University of Bologna |
Paolini S.,University of Bologna |
And 16 more authors.
Cancer | Year: 2014
BACKGROUND Patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) frequently relapse on imatinib with acquisition of BCR-ABL kinase domain (KD) mutations. To analyze the changes that second-generation tyrosine kinase inhibitors (TKIs) have brought in mutation frequency and type, a database review was undertaken of the results of all the BCR-ABL KD mutation analyses performed in the authors' laboratory from January 2004 to January 2013. METHODS Interrogation of the database retrieved 450 mutation analyses in 272 patients with Ph+ ALL. Prescreening of samples was performed with denaturing high-performance liquid chromatography (D-HPLC), followed by direct sequencing of D-HPLC-positive cases. RESULTS BCR-ABL KD mutations were detected in 70% of imatinib-resistant patients, with T315I, E255K, and Y253H mutations accounting for 75% of cases. Seventy-eight percent of the patients reported to be resistant to second-generation TKIs after imatinib failure were positive for mutations, and 58% of them had multiple mutations. Analysis of patients relapsing on dasatinib revealed a newly acquired T315I mutation in almost two-thirds of the cases. Direct sequencing detected no mutations at diagnosis, even in patients who relapsed after a few months. CONCLUSIONS Second-generation TKIs ensure a more rapid debulking of the leukemic clone and have much fewer insensitive mutations, but long-term disease control remains a problem, and the T315I mutation is revealed to be an even more frequent enemy. BCR-ABL KD mutation screening of patients with Ph+ ALL who are receiving imatinib or second-generation TKIs would be a precious ally for timely treatment optimization. In contrast, the clinical usefulness of conventional direct sequencing at diagnosis seems to be very low. © 2013 American Cancer Society.
Amedei A.,University of Florence |
Munari F.,Venetian Institute of Molecular Medicine |
Bella C.D.,University of Florence |
Niccolai E.,University of Florence |
And 9 more authors.
Internal and Emergency Medicine | Year: 2014
Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma. The cytokine profile and the effector functions of gastric tumor-infiltrating lymphocytes (TILs) specific for HP0175 was investigated in 20 patients with distal gastric adenocarcinoma and H. pylori infection. The helper function of HP0175-specific TILs for monocyte MMP-2, MMP-9, and VEGF production was also investigated. TILs cells from H. pylori infected patients with distal gastric adenocarcinoma produced Interleukin (IL)-17 and IL-21 in response to HP0175. HP0175-specific TILs showed poor cytolytic activity while expressing helper activity for monocyte MMP-2, MMP-9 and VEGF production. These findings indicate that HP0175 is able to drive gastric Th17 response. Thus, HP0175, by promoting pro-inflammatory low cytotoxic TIL response, matrix degradation and pro-angiogenic pathways, may provide a link between H. pylori and gastric cancer. © 2012 SIMI.
Pallotta S.,University of Florence |
Simontacchi G.,AOU Careggi |
Marrazzo L.,AOU Careggi |
Ceroti M.,U.O. Epidemiologia Molecolare e Nutrizionale ISPO |
And 3 more authors.
Medical Physics | Year: 2013
Purpose: The aim of this paper is to investigate the accuracy of a laser/camera surface imaging system (Sentinel) when used on patients treated in the thorax or pelvic regions and to evaluate system employment conditions and patient setup procedures that provide more accurate results. Methods: The system was tested on two groups of patients for whom different patient setup procedures and Sentinel employment conditions were considered. For the first group of 33 patients (FG) no changes to the usual setup procedures were made and a surface extension limited to the treated region was considered. For the second group of 14 patients (SG) the reproducibility of external body surfaces, including body parts not in close proximity to the treatment site, was optimized and a wider surface was captured. In all cases the system accuracy was evaluated comparing registration results from concurrent Sentinel and cone beam CT (CBCT) acquisitions for a total of 192 occasions. External body surfaces, extracted from planning CT studies, were used as reference in both cases, but for SG also surface data captured by Sentinel system at the first treatment were employed. Results: In the 90th percentile of the distributions reporting CBCT and Sentinel registration parameters, absolute differences for FG were less than 6.4 mm and 3.8°. Better performances were observed for SG (≤5.7 mm and 2°). Mean absolute differences between three translation and three rotation parameters of CBCT and Sentinel were: less than 3.5 mm and 2.1° and 3.7 mm and 1.3° in FG for thorax and pelvis, respectively, and less than 2.8 mm and 1° and 2.7 mm and 0.9° for pelvis and thorax, respectively, in SG. No advantage in considering surface data captured by Sentinel as a reference instead of the surface extracted from the planning CT was observed. Conclusions: The accuracy of Sentinel system in detecting errors is influenced by the extension and reliability of the surface used. When the reproducibility of external body surfaces was optimized differences between CBCT and Sentinel registration parameters resulted less than 5.7 mm and 2° in the 90% of the pelvis and thorax considered cases. No advantage in considering a Sentinel acquisition as reference was observed. © 2013 American Association of Physicists in Medicine.
PubMed | Onkologische Praxis, Kedrion S.p.A., Onkologie, University of Naples Federico II and 2 more.
Type: | Journal: International immunopharmacology | Year: 2017
Intravenous immunoglobulin (IVIg) is accepted as an effective and well-tolerated treatment for primary and secondary immunodeficiencies (ID) and immune thrombocytopenia (ITP). Adverse reactions of IVIg are usually mild, comprising transient flu-like symptoms, change in blood pressure and tachycardia. However IVIg therapy can be burdensome for both patients and healthcare facilities, since the infusion may take up to 4h to administer. The objective of our multicentre, prospective, open-label phase III trial was to evaluate the tolerability and safety of human normal immunoglobulin 50g/l (Ig VENA) at high intravenous infusion rates in adult patients with ID and ITP who had previously tolerated IVIg treatment, by progressively increasing infusion rate up to 8ml/kg/hr. 39 ID patients received three infusions, 5 ITP patients received up to a maximum of 5 infusions for a maximum of 5days. Overall 55 adverse events were reported in 18 patients, and all were mild and self-limiting. Two serious adverse events occurred in ID patients and 1 in an ITP patient; none was fatal or treatment-related. No clinically significant changes or abnormalities were observed in vital signs, laboratory results and HRQoL. In summary, in this study, more rapid IVIg infusions were well tolerated by ID and ITP patients, while maintaining their quality of life, helping to minimise the time spent in outpatient hospital visiting to potentially optimise adherence to treatment.
Palareti G.,University of Bologna |
Poli D.,AOU Careggi
Expert Review of Cardiovascular Therapy | Year: 2016
For many decades vitamin K antagonists (VKA), whilst extremely effective but associated with significant drawbacks, were the only drugs available for chronic anticoagulation. However, recently, novel direct oral anticoagulant drugs, completely different to VKA and at least as effective and safe as VKA, have been introduced in clinical practice and their use is becoming increasingly more widespread. Their availability can extend effective anticoagulant treatment to a larger number of subjects requiring anticoagulation and substantially improve the quality of life of many patients. However, these drugs and their use also have limitations. The aim of this article is to analyze these limitations and the challenges potentially associated with their use, a move crucial to promote proper, effective and safe use of the drugs in everyday practice. © 2015 Taylor & Francis.
Latiano A.,Laboratorio Of Gastroenterologia |
Annese V.,AOU Careggi
Current Drug Targets | Year: 2011
Substantial progress has been made in the last years in characterizing the susceptibility genes involved in IBD pathogenesis, especially for Crohn's disease. Although some genetic factors associated with Crohn's disease also predispose individuals to ulcerative colitis, markers specific only for ulcerative colitis have been found. Recent genomewide association studies in ulcerative colitis have identified several new loci, and suggested many new potential pathways. The identified susceptibility genes and their variants could be useful to predict disease course and to improve stratification of patients, when correlated with other subphenotypes. Moreover, understanding the biological pathways involved in the disease could lead to the development of new treatments and molecules that specifically target such pathways, discover different therapeutic approaches and eventually progress to personalized treatment. © 2011 Bentham Science Publishers Ltd.
Bergamini C.,AOU Careggi
Il Giornale di chirurgia | Year: 2010
Laparoscopic adrenal surgery has significantly improved during the last years. Thus at the moment it is possible to define such technique as the therapeutic "Gold Standard" option in the treatment of the adrenal tumors. However, some doubts are still remaining concerning the feasibility of laparoscopic adrenalectomy in case of malignant adrenal tumors, hyper-vascular tumors (pheochromocytoma) and indeterminate incidentaloma. This study aimed to review all the literature of the last three years (only article with abstracts) using the criteria of selection of the Cochrane Library, in order to find class I and class II-III studies which are able to surely or, respectively, probably respond to the various questions yet to be answered Two hundred and twelve papers have been selected. The class I studies stated the following evidences: laparoscopic treatment of pheochromocytoma is the Gold Standard too, independently from the dimension; the short term results of laparoscopic anterior and posterior approach are equivalent to those of the lateral one. Doubts still remain concerning the role of laparoscopy in the treatment of metastases, big pheochromocytomas, small size incidentalomas (risk of over-treatement). Nearly no respond has been given to others issues such as "the single port techniques" in laparoscopic adrenalectomy, the role of radiofrequency laparoscopic ablation of the adrenal tumor, the kind of treatment of stadium I and II adrenocortical carcinoma and big size (> 8 cm) tumors, the management of non-functioning incidentaloma of 4-6 cm, the role of the robot, and, finally, the approach of the bilateral tumors. We conclude that, despite many issues on the feasibility and safety of laparoscopy in the adrenal surgery have been definitely clarified, so that such technique has been declared the "Gold Standard" method in the treatment of the adrenal tumor, doubts still remain in some aspects of this method. However, since the researches in this field are proceeding with high evolution velocity, in the next future most of the questions that are still present should be definitively adressed.