San Giovanni Rotondo, Italy
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Lin D.,Michael bakey Veterans Affairs Medical Center | Verstovsek G.,Michael bakey Veterans Affairs Medical Center | Verstovsek G.,Baylor College of Medicine | Rugge M.,University of Padua | And 5 more authors.
American Journal of Gastroenterology | Year: 2013

OBJECTIVES: This study examined Barrett's esophagus (BE) risk factors in veterans to determine the association between risk of BE and use of oral bisphosphonates. METHODS: We conducted a case-control study among eligible patients scheduled for an elective esophagogastroduodenoscopy (EGD) and a sample of patients eligible for screening colonoscopy recruited from primary care clinics from a single VA Medical Center. Cases with definitive BE were compared with controls; all underwent study EGD. Use of oral bisphosphonates was ascertained by reviewing filled prescriptions in electronic pharmacy records. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs), using multivariate logistic regression modeling while adjusting for sex, age, race, proton-pump inhibitor use, hiatal hernia, waist-to-hip ratio, Helicobacter pylori infection, and gastroesophageal reflux disorder (GERD) symptoms. RESULTS: There were 285 BE cases, 1,122 endoscopy controls, and 496 primary care controls. Alendronate and risedronate were the only oral bisphosphonates prescribed. The proportion of BE cases with filled prescription of oral bisphosphonates (4.6%) was greater than in endoscopy controls (1.6%) or primary care controls (2.9%). In the adjusted analysis, oral bisphosphonate use was significantly associated with BE risk (OR=2.33; 95% CI: 1.11-4.88) compared with the combined control groups. This association remained significant when BE cases were compared with endoscopy controls only (OR=2.74; 95% CI: 1.28-5.87) but was attenuated when compared with primary care controls only (OR=2.60; 95% CI: 0.99-6.84). The association was observed in patients with GERD symptoms (OR=3.29; 95% CI: 1.36-7.97) but not in those without GERD symptoms. CONCLUSION: Oral bisphosphonate use may increase the risk for BE, especially among patients with GERD. © 2013 by the American College of Gastroenterology.


Milone G.,Programma di Trapianto Emopoietico | Milone G.,Instituto Oncologico del Mediterraneo | Martino M.,Programma Trapianto di Midollo | Spadaro A.,Programma di Trapianto Emopoietico | And 8 more authors.
British Journal of Haematology | Year: 2014

Summary: To date, no prospective study on Plerixafor 'on-demand' in combination with chemotherapy and granulocyte colony-stimulating factor (G-CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on-demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G-CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34+ cells in peripheral blood was reduced by 'on-demand' strategy compared to conventional mobilization; from 13·0 to 3·0% (P = 0·004). Failure to harvest CD34+ cells 2 × 106/kg decreased from 20·9 to 4·0% (P = 0·0001). The on-demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0·03) and harvest failure (P = 0·0008) when compared to a 'bias-adjusted set of controls'. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G-CSF, the 'on-demand' use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost. © 2013 John Wiley & Sons Ltd.


Ferrari D.,University of Milan Bicocca | Zalfa C.,University of Milan Bicocca | Nodari L.R.,University of Milan Bicocca | Gelati M.,Casa Sollievo della Sofferenza | And 6 more authors.
Cellular and Molecular Life Sciences | Year: 2012

Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications. © 2011 Springer Basel AG.


News Article | December 2, 2015
Site: www.nature.com

Italian politicians have kindled the wrath of some biomedical scientists by hand-picking a stem-cell clinical trial for funding. The €3-million (US$3.2-million) pot for the trial should be allocated through an open competition based on scientific merit rather than in an amendment to the country’s 2016 budget bill, say the researchers. They are appealing to Italy’s Parliament to change the amendment — which the Senate approved on 20 November — before it passes into law. To many Italian scientists, the idea that certain projects receive funding at the whim of politicians feels depressingly familiar. In 2013, a government decree earmarked this money for a stem-cell clinical trial run by a specific clinic. That earlier allocation was to the controversial Stamina Foundation in Brescia, and was later abandoned after a fraught, year-long campaign by scientists who convinced the health ministry that the trial was based on bad science and illegal practices. In the objections to the amendment to the 2016 budget bill, there is no suggestion of scientific wrongdoing, but researchers take issue with the way that the trial selection was made. “Italian politicians can take a liking to a project and then finance it directly,” says Marino Zerial, a director at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany. He is one of 29 researchers who signed a letter published in the newspaper La Stampa on 26 November calling for the budget-law amendment to be changed. “Where do you see this in any other country?” After the Stamina trial was abandoned, many Italian scientists assumed that politicians would never again earmark specific research projects for public funding. The Constitutional Court, reflecting on the Stamina debacle, stated that the selection of clinical trials to receive public funding should not be at the “pure political discretion of the legislator”. The amendment to the 2016 budget law does not name a specific trial: it states that the money should be given for a “phase II clinical trial based on the transplantation of human neural stem cells in patients affected with Amyotrophic Lateral Sclerosis” (ALS), a deadly neuro­degenerative condition also known as motor neuron disease. But of the 11 stem-cell protocols that have been approved for early-phase clinical trials in Italy, only one meets these criteria — so the outcome amounts to a selection in practice, says Giuseppe Remuzzi, director of the Mario Negri Institute for Pharmacological Research in Bergamo, one of the letter’s signatories. The protocol comes from the lab of stem-cell researcher Angelo Vescovi, scientific director of the Casa Sollievo della Sofferenza research hospital in the southern Italian province of Foggia. It involves transplanting neurons derived from the brains of miscarried fetuses into the spinal cords of people with ALS. Senator Giorgio Santini, who proposed the amendment, told Nature that the way it had been selected and added to the bill was procedurally correct and that, if signed into law, the amendment would help sick people. He added that, in principle, any scientist who met the criteria could apply for the money, but that Vescovi’s trial is the only one that is ready to be implemented. Vescovi declined to comment on the fact that his work was proposed for funding, but noted that Santini was present at a public meeting in Rome on 29 September, where Vescovi presented the final results of his phase I ALS trial. Unlike the criticisms levelled against the Stamina trial, the scientists who wrote the letter complaining about the amendment told Nature that they are not commenting on the quality of Vescovi’s research. They point out that a phase I trial in six patients that assessed the safety of the therapy was carried out with appropriate oversight of the health authorities (L. Mazzini et al. J. Transl. Med. 13,17; 2015). Their concerns lie with how the trial was selected, which is particularly painful because Italy’s funds for research are among the lowest in Europe, and the 2016 budget foresees no increase for public institutions. “Scarce resources should be allocated to the most absolute transparency rules”, they write. Remuzzi says that the criteria were so narrow that scientists like himself could not apply. “We ourselves have three stem-cell trials related to organ transplantation,” he says. “We should have had the opportunity to apply.” Patient groups have also objected to the way the funding was allocated, saying that therapies for other illnesses should have been allowed to compete. The Italian Multiple Sclerosis Foundation in Genoa has sent politicians evidence of other ready-to-go Italian stem-cell trials for various neuro­degenerative diseases. And the Italian Association for Huntington’s Chorea in Milan complained to the Chamber of Deputies — Italy’s second parliamentary house, which will vote on the budget bill next — that the amendment appeared without revealing the scientific criteria used to select one clinical trial from among other candidates. Scientists hope that their outcry will encourage the Chamber of Deputies to drop or modify the amendment in the next week or so. Time is tight: the 2016 budget law is linked to a confidence vote in the government, which means that Parliament is under pressure to approve it before the end of the year.


Becattini C.,University of Perugia | Agnelli G.,University of Perugia | Schenone A.,Galliera Hospital | Eichinger S.,Medical University of Vienna | And 8 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown. METHODS:In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome. RESULTS:Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups. CONCLUSIONS: Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677.) Copyright © 2012 Massachusetts Medical Society.


Garatti A.,IRCCS Policlinico San Donato Hospital | Mori F.,IRCCS Policlinico San Donato Hospital | Innocente F.,IRCCS Policlinico San Donato Hospital | Canziani A.,IRCCS Policlinico San Donato Hospital | And 6 more authors.
Annals of Thoracic Surgery | Year: 2011

Background We sought to evaluate the long-term performance of a consecutive cohort of patients implanted with a 17-mm bileaflet mechanical prosthesis. Methods Between January 1995 and December 2005, 78 patients (74 women, mean age = 71 ± 12 years) underwent aortic valve replacement with a 17-mm mechanical bileaflet prosthesis (Sorin Bicarbon-Slim and St. Jude Medical-HP). Preoperative mean body surface area and New York Heart Association class were 1.6 ± 0.2 m2 and 2.6 ± 0.8, respectively. Preoperative mean aortic annulus, indexed aortic valve area, and peak and mean gradients were 18 ± 1.6 mm, 0.42 cm2/m2, 89 ± 32 mm Hg, and 56 ± 21 mm Hg, respectively. Patients were divided into two groups, according to the presence (group A, 29 patients) or absence of patientprosthesis mismatch (group B, 49 patients). Patientprosthesis mismatch was defined by an indexed effective orifice area less than 0.85 cm2/m2. Results Overall hospital mortality was 8.8%. Follow-up time averaged 86 ± 44 months. Actuarial 5-year and 10-year survival rates were 83.7% and 65.3%, respectively. The mean postoperative New York Heart Association class was 1.3 ± 0.6 (p < 0.001). Overall indexed left ventricular mass decreased from 163 ± 48 to 120 ± 42 g/m2 (p < 0.001), whereas average peak and mean prosthesis gradients were 28 ± 9 mm Hg and 15 ± 6 mm Hg, respectively (p < 0.001). Early and long-term mortality were similar between the two groups as well as long-term hemodynamic performance (mean peak gradient was 28 mm Hg and 27 mm Hg in group A and B, respectively, not significant); left ventricular mass regression occurred similarly in both groups (indexed left ventricular mass at follow-up was 136 ± 48 and 113 ± 40 in group A and B, respectively; not significant). Conclusions Selected patients with aortic stenosis experience satisfactory clinical improvement after aortic valve replacement with modern small-diameter bileaflet prostheses. © 2011 The Society of Thoracic Surgeons.


Sealock R.J.,Michael bakey Veterans Affairs Medical Center | Sealock R.J.,Baylor College of Medicine | Kramer J.R.,Michael bakey Veterans Affairs Medical Center | Kramer J.R.,Baylor College of Medicine | And 8 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2013

Background Oesophageal eosinophilia (EE) is encountered in clinical practice as oesophageal biopsies are being obtained in patients with GI symptoms other than classical symptoms of eosinophilic oesophagitis (EoE). The prevalence, determinants and clinical relevance of EE identified irrespective of symptoms are unclear. Aim To determine the prevalence and risk factors of EE with or without EoE in a nonselected group of patients undergoing endoscopy and in primary care patients. Methods A cross-sectional study in a single VA centre in which we obtained at least one oesophageal biopsy from patients presenting to elective endoscopy, as well as a sample of patients eligible for screening colonoscopy recruited from primary care clinics. EE was defined by >15 eosinophils in a single HPF; and EoE was defined as definite, probable or none depending on the presence of EE, acid-suppressive therapy and oesophageal symptoms. Results EE was identified in 33 of 1357 patients (2.4%, 95% CI: 1.7-3.4); of whom 9 had definite EoE (0.66%, 95% CI: 0.23-1.10), 17 had probable EoE (1.25%), and the only 7 patients had EE without EoE. The prevalence of EE was 2.3% among patients undergoing elective endoscopy and 0.1% among patients eligible for screening colonoscopy. Seasonal allergies (adjusted OR: 2.78; 95% CI: 1.26-6.11) and oesophageal strictures (4.50; 0.90-22.40) were associated with EE. Conclusions The prevalence of EE was 2.3% among unselected patients presenting to endoscopy most of whom have EoE. EE was present in 0.1% in primary care patients none of whom had EoE. © 2013 Blackwell Publishing Ltd.


Pellicano R.,Casa Sollievo della Sofferenza | Caldarola G.,Catholic University of the Sacred Heart | Filabozzi P.,Casa Sollievo della Sofferenza Hospital | Zalaudek I.,Dermatology and Skin Cancer Unit | Zalaudek I.,Medical University of Graz
Dermatology | Year: 2013

Background: Dermoscopy is traditionally used for the diagnosis of skin tumors, but it has also gained increasing interest as an adjunct in the clinical diagnosis of inflammatory skin diseases. Objective: To evaluate the dermoscopic patterns of necrobiosis lipoidica (NL) and granuloma annulare (GA) and to compare these findings with other granulomatous skin disorders. Methods: This is a retrospective analysis of patient data and clinical and dermoscopic images of histopathologically diagnosed cases of NL and GA. Results: A total of 24 cases, including 12 cases of NL and 12 cases of GA, were evaluated. In all cases of NL, dermoscopy revealed evident, sharply focused, elongated and serpentine telangiectasias, which were typically located over a whitish, structureless background. In contrast, all cases of GA were dermoscopically typified by peripheral, structureless orange-reddish borders, which were associated in 5 cases with isolated, unfocussed small vessels. Conclusion: Our study suggests that NL and GA reveal different dermoscopic patterns, which may aid the correct diagnosis. In addition, the dermoscopic patterns of NL and GA appear to differ from other forms of granulomatous diseases. © 2013 S. Karger AG, Basel.


Eslam M.,University of Sydney | Leung R.,University of Sydney | Romero-Gomez M.,Hospital Universitario Of Valme | Mangia A.,Ospedale Casa Sollievo della Sofferenza | And 15 more authors.
Journal of Hepatology | Year: 2014

Background & Aims Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients. Methods The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917. Results Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG). Conclusions This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.


Lorusso D.,Catholic University of the Sacred Heart | Pietragalla A.,Catholic University of the Sacred Heart | Mainenti S.,Catholic University of the Sacred Heart | Masciullo V.,Catholic University of the Sacred Heart | And 2 more authors.
Critical Reviews in Oncology/Hematology | Year: 2010

Background: Ovarian cancer is the fourth cause of death from gynaecological cancer and cervical cancer is the first in women <45 years old in developing countries.The aim of this article is to review the role of topotecan (Hycamtin®), a semi-synthetic alkaloid derivative of camptothecin, in ovarian and cervical cancer in monotherapy and in combination. Methods: This article reviews the mechanism of action, pharmacokinetics, toxicity and efficacy of topotecan. The paper also reports the principal phases II and III studies of topotecan in advanced or recurrent ovarian and cervical cancer. Results: Topotecan (Hycamtin®), currently indicated for the treatment of relapsed ovarian cancer, has demonstrated activity both in platinum-sensitive and in platinum-resistant disease. The combination cisplatin-topotecan for the treatment of advanced and recurrent cervical cancer has demonstrated a clinical benefit in terms of response rate, overall survival and progression free survival. Haematological toxicity of topotecan also is easy to manage and not cumulative, especially with the weekly scheduled recently introduced in clinical practice. Conclusion: Topotecan (Hycamtin®) will continue to play a role in the treatment of advanced ovarian and cervical cancer, in monotherapy or in combination with other cytotoxic agents. © 2009 Elsevier Ireland Ltd.

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