Bozzo C.,University of Piemonte Orientale |
Tiberio R.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Graziola F.,University of Piemonte Orientale |
Pertusi G.,University of Piemonte Orientale |
And 4 more authors.
Microbes and Infection | Year: 2010
The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) depends on cytotoxic effect of its exotoxin mycolactone. Since epidermis represents a barrier against infectious agents and balanced apoptosis is essential in epidermal homeostasis, we explored if mycolactone A/B induces apoptosis on two human keratinocyte populations, stem cells (KSC) and transit amplifying cells (TAC), and on human keratinocyte line, HaCaT. Treatment of TAC with 1 and 10 ng/ml mycolactone-induced 60 and 90% apoptosis. KSC were more resistant than TAC: 50 and 75% of cells underwent apoptosis after 10 and 100 ng/ml toxin-treatment. Higher doses (1000 ng/ml) induced about 30% apoptosis on HaCaT. In contrast, mycolactone A/B was devoid of toxicity neither on human hepatoma HuH7 nor on human embryonic kidney HEK 293 T cell lines. In conclusion, mycolactone induces apoptosis in human keratinocytes, thus contributing to Buruli ulcer lesions development. © 2010 Institut Pasteur.
Sutti S.,Health Science University |
Rigamonti C.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Vidali M.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Albano E.,Health Science University
Redox Biology | Year: 2014
Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression. © 2014.
Armellini E.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Crino S.F.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Orsello M.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Ballare M.,Azienda Ospedaliero Universitaria Maggiore della Carita |
And 4 more authors.
World Journal of Gastroenterology | Year: 2015
This paper reports our experience with a new overthe- scope clip in the setting of recurrent bleeding and oesophageal fistula. We treated five patients with the over-the-scope Padlock Clip™. It is a nitinol ring, with six inner needles preassembled on an applicator cap, thumb press displaced by the Lock-It™ delivery system. The trigger wire is located alongside the shaft of the endoscope, and does not require the working channel. Three patients had recurrent bleeding lesions (bleeding rectal ulcer, post polypectomy delayed bleeding and duodenal Dieulafoy's lesion) and two patients had a persistent respiratory-esophageal fistula. In all patients a previous endoscopic attempt with standard techniques had been useless. All procedures were conducted under conscious sedation but for one patient that required general anaesthesia due to multiple comorbidities. We used one Padlock Clip™ for each patient in a single session. Simple suction was enough in all of our patients to obtain tissue adhesion to the instrument tip. A remarkably short application time was recorded for all cases (mean duration of the procedure: 8 min). We obtained technical and immediate clinical success for every patient. No major immediate, early or late (within 24 h, 7 d or 4 wk) adverse events were observed, over follow-up durations lasting a mean of 109.4 d. One patient, treated for duodenal bulb bleeding from a Dieulafoy's lesion, developed signs of mild pancreatitis 24 h after the procedure. The new over-the-scope Padlock Clip™ seems to be simple to use and effective in different clinical settings, particularly in "difficult" scenarios, like recurrent bleeding and respiratory-oesophageal fistulas. © 2015 Baishideng Publishing Group Inc. All rights reserved.
Vivirito M.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Conocchia M.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Patane R.,Azienda Ospedaliero Universitaria Maggiore della Carita |
Micalizzi E.,Azienda Ospedaliero Universitaria Maggiore della Carita
Texas Heart Institute Journal | Year: 2015
We describe the case of a 62-year-old man who needed a 3-vessel coronary artery bypass reoperation and mitral valve replacement. The patient’s existing free left internal mammary artery graft was not functioning because of a critical stenosis in the native vessel just after the distal anastomosis. The free graft itself was in perfect condition, and we decided to reuse it. Because the course of the graft was so tortuous, we concluded that skeletonization would yield the extra length needed for reimplantation. After reimplanting the graft, we performed venous grafting and mitral valve replacement. The patient was well and had no signs of ischemia at 29 months postoperatively. There have been few reports on recycling internal mammary artery grafts in repeat coronary artery bypass grafting. To our knowledge, ours is the first report of the reimplantation of a free internal mammary artery graft on the same vessel. We describe the procedure and our decision-making process. © 2015 by the Texas Heart ® Institute, Houston.
PubMed | University of Padua, UOC Pediatria, Sandoz S.p.A, University of Bari and 11 more.
Type: Journal Article | Journal: Italian journal of pediatrics | Year: 2016
PATRO Children is an ongoing observational, longitudinal, non-interventional, global post-marketing surveillance study, which is investigating the long-term safety and effectiveness of Omnitrope, a somatropin biosimilar to Genotropin, in children with growth disturbances. The primary endpoint of PATRO Children is long-term safety and the secondary endpoint is effectiveness, which is assessed by analysing auxological data such as height (HSDS) and height velocity (HVSDS) standard deviation scores. Here, we report the data from the Italian interim analysis of PATRO Children data up to August 2015.PATRO Children is enrolling children who are diagnosed with conditions of short stature requiring GH treatment and are receiving Omnitrope. Adverse events (AEs) are assessed in all Omnitrope-treated patients. Height is evaluated yearly to near-adult (final) height, and is herein reported as HSDS; height velocity is also assessed and reported as a standard deviation score (HVSDS).Up to August 2015, a total of 186 patients (mean age 10.2years, 57.5% males) were enrolled :156 [84%] had growth hormone deficiency, 12 [6.5%] were born small for gestational age, seven [3.8%] had Prader-Willi syndrome, one [0.5%] had Turner syndrome and one [0.5%] had chronic renal insufficiency; seven [3.8%] patients had other indication profiles. The mean treatment duration with Omnitrope was 28.119.1months. AEs were reported in 35.6% of patients and included headache, pyrexia, arthralgia, abdominal pain, leg and/or arm pain and increased blood creatine phosphokinase. Two serious AEs in two patients were thought to be drug-related; one patient experienced a minimal increase in a known residual craniopharyngioma, and another a gait disturbance with worsening of walking difficulties. Similar to investigational studies, Omnitrope treatment was associated with improvements in both HSDS and HVSDS.Omnitrope appears to be well tolerated and effective for the treatment of a wide range of paediatric indications, which is consistent with the outcomes from controlled clinical trials. These results need to be interpreted with caution until the data from the global PATRO Children study are available.
PubMed | Azienda Ospedaliero Universitaria Maggiore della Carita
Type: Journal Article | Journal: Minerva anestesiologica | Year: 2015
Osteopontin (OPN) and soluble urokinase plasminogen activator receptor (suPAR) have been proposed as markers of disease severity and risk-stratification in infection and inflammation. In breast cancer, OPN and the membrane bound form of urokinase plasminogen activator receptor (uPAR) are functionally related, as OPN-induced cell migration depends on uPAR triggering by urokinase plasminogen activator (uPA). The aim of this study was to prospectively evaluate the kinetic of OPN and suPAR blood levels in patients developing septic shock (SS) compared to those not developing SS, and to investigate the relationships between these two biomarkers in immune cells in vitro.We measured the levels of OPN and suPAR for 15 days in forty-three patients, defined a priory as at risk to develop septic shock. Moreover, we investigated in vitro the effect of recombinant OPN on uPAR and suPAR expression in monocytes.We found that OPN and suPAR levels were directly correlated to each other both at intensive care unit admission and on the day patients met SIRS/sepsis or septic shock criteria. In patients developing septic shock, OPN increased prior to suPAR and was already detectable up to 4 days before the shock development. In vitro, OPN induced suPAR production in monocytes by increasing both uPAR gene expression, and suPAR release from the cell surface.These data suggest that OPN is partly responsible for the increased plasma levels of suPAR and might be a valuable tool to predict the occurrence of septic shock.
PubMed | Umberto I Hospital, University of Bari, University of Naples Federico II, San Giovanni Bosco Hospital and 4 more.
Type: Journal Article | Journal: Journal of neurointerventional surgery | Year: 2016
Experience with the endovascular treatment of cerebral aneurysms using the p64 Flow Modulation Device is still limited. This study discusses the results and complications of this new flow diverter device.40 patients (30 women, 10 men) with 50 cerebral aneurysms treated in six Italian neurointerventional centers with the p64 Flow Modulation Device between April 2013 and September 2015 were retrospectively reviewed.Complete occlusion was obtained in 44/50 aneurysms (88%) and partial occlusion in 3 (6%). In the other three aneurysms (6%), two cases of asymptomatic in-stent thrombosis and one intraprocedural occlusion of the parent vessel occurred. Technical complications were observed in eight procedures (16%). Permanent morbidity due to acute in-stent thrombosis and consequent ischemic stroke occurred in one patient (2.5%). No delayed aneurysm rupture, subarachnoid or intraparenchymal hemorrhage, or ischemic complications occurred and there were no deaths.Endovascular treatment with the p64 Flow Modulation Device is a safe treatment for unruptured cerebral aneurysms, resulting in a high rate of occlusion. As with other flow diverter devices, we recommend this treatment mainly for large-necked aneurysms of the internal carotid artery siphon. However, endovascular treatment with the p64 device should also be encouraged in difficult cases such as aneurysms of the posterior circulation and beyond the circle of Willis.
Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24months and immunogenicity of a fifth dose administered at 4years of age-a phase 3 extension to a randomised controlled trial
PubMed | St George's, University of London, University of Bristol, Vaccine Research Area, Novartis and 5 more.
Type: Journal Article | Journal: Vaccine | Year: 2016
4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24months and characterised the antibody response to a fifth dose administered at 4years of age.A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-nave or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-nave and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6month schedule.At baseline (prior to vaccination), the proportion of participants (n=468) with hSBA titers5 was similar across all followon groups: 89-100% against 5/99; 12-35% for H44/76; 8-12% for NZ98/254 and 53-80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-nave controls (n=206). Following a dose of 4CMenB at 4years of age, this increased to 100% (5/99), 97-100% (H44/76), 80-95 % (NZ98/254) and 84-100% (M10713) (n=210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-nave controls (n=192).Waning of protective antibodies occurred 12-36months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4years of age.
PubMed | Azienda Ospedaliero Universitaria Maggiore della Carita and University of Piemonte Orientale
Type: Journal Article | Journal: Internal and emergency medicine | Year: 2016
Non-invasive ventilation (NIV) delivered in an intensive care unit (ICU) has become the cornerstone in the treatment of patients with severe chronic obstructive pulmonary disease (COPD) exacerbations. A trend towards managing these patients in non-ICU setting has emerged in recent years, although out-of-hospital survival by this approach and how to prognosticate it is unknown. We aimed to investigate these issues. We consecutively recruited 100 patients (49 males; median age 82years) who received NIV treatment for acute respiratory failure due to COPD exacerbation in non-ICU medical wards of our hospital, between November 2008 and July 2012. We assessed survival (both in-hospital and out-of-hospital) of all these patients, and analyzed baseline parameters in a Cox proportional hazards model to develop a prognostic score. The median survival in the study population was 383days (240-980). Overall survival rates were 71.0, 65.3, and 52.7% at 1, 3, and 12months, respectively. Age>85years, a history of heart disorders and a neutrophil count1010(9) were associated with higher mortality at Coxs analysis ( (2)=35.766, p=0.0001), and were used to build a prognostic score (NC85). The presence of two or more factors determined the deepest drop in survival (when NC852, mortality at 1, 3, and 12 was 60.7, 70.4, and 77.2%, respectively, while when NC85=0 were 4.0, 4.0, and 14.0%). A simple model, based on three variables (age, neutrophil count and history of heart disease), accurately predicts survival of COPD patients receiving NIV in a non-ICU setting.
PubMed | University of Padua, University of Genoa, University of Milan Bicocca, Pathology Unit and 15 more.
Type: Journal Article | Journal: Cancer medicine | Year: 2016
Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a double hit score upon positivity for BCL2 and MYC. PCDLBCL-NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B-cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a non-germinal B-cell profile, whereas germinal center cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC-LT, which often coexpressed MYC and BCL2. The impact of single factors on 5-year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group-PCDLBCL-NOS-exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.