Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactor... more Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02-1.43] and 1.27 [1.05-1.53]), diabetes mellitus (odds ratio, 2.35 [1.68-3.29] and 2.12 [1.47-3.05]), chronic constipation (odds ratio, 1.60 [1.30-1.97] and 1.55 [1.23-1.94]), incomplete purge intake (odds ratio, 2.36 [1.90-2.94] and 2.11 [1.68-2.65]) and a runway time >12h (odds ratio, 3.36 [2.40-4.72] and 2.53 [1.74-3.67]). We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.
In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroente... more In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, Jan 14, 2015
Serrated lesions are recognized as important contributors to colorectal cancer incidence. We aime... more Serrated lesions are recognized as important contributors to colorectal cancer incidence. We aimed to prospectively assess the prevalence of serrated lesions and identify potential predictors of these lesions during colonoscopy in an Italian population. Prospective cross sectional study involving 8 endoscopy units from February 1st to July 31st 2012. Out of 2468 colonoscopies, 886 precancerous lesions were detected in 567 patients. Of these, 173 SELs were diagnosed in 148 patients (140 serrated/hyperplastic polyps and 33 serrated adenomas). Prevalence was 7% (173/2468). Serrated lesions accounted for 19.5% of all precancerous lesions. Serrated polyps were prevalent in the left colon (42.1%) and serrated adenomas in the proximal colon (54.5%). Independent clinical predictors of serrated lesions were patient age (OR 0.98 [0.97-1.00]) and post-polypectomy surveillance (OR 1.87 [1.24-2.82]). Endoscopic predictors were right colon location (OR 2.65 [1.63-4.30] vs. rectum; and 1.53 [1.03-...
Endoscopic treatment with combined modalities is considered standard of care for patients with hi... more Endoscopic treatment with combined modalities is considered standard of care for patients with high-risk peptic ulcer bleeding. This study compared epinephrine injection plus bipolar probe coagulation with bipolar probe coagulation alone in patients with high-risk peptic ulcer bleeding. Patients with endoscopically confirmed peptic ulcer bleeding (active or visible vessel) seen from January 2000 through December 2002 were prospectively randomized to two groups. The study group (n = 58) had epinephrine injection followed by bipolar coagulation; the control group (n = 56) was treated by bipolar coagulation alone. The primary outcomes assessed were the rate of initial hemostasis and the rate of recurrent bleeding. Secondary outcomes were the following: need for surgical intervention to control bleeding, transfusion requirements, length of hospital stay (in days), and 30-day mortality. The rate of initial hemostasis was significantly higher in the combination therapy group ( p = 0.02; a...
The role of glial cells to the pathogenesis and maintenance of persistent pain is largely recogni... more The role of glial cells to the pathogenesis and maintenance of persistent pain is largely recognized but yet poorly elucidated. Mechanisms linking reactive gliosis to neuropathic pain are just emerging, reshaping the current understanding of pain circuitry and sensory processing. This process involves the activation of glial cells, resulting in the reactive gliosis, that in turn facilitates the release of pro-nociceptive mediators (e.g. ATP, glutamate, cytokines) that activate and sensitize spinal dorsal horn neurons. Evidence from a variety of experimental models indicated the activation of ATP purinergic P2X receptor subtypes, including P2X7, mostly expressed on glial cells, as a mechanism modulating pain perception, suggesting that purinergic neuro-glial interactions are important modulators of sensory neurotransmission. In this study, we used the sciatic spared nerve injury (SNI) model of neuropathic pain in rats as a tool to induce reactive gliosis in the dorsal horn of lumbar ...
Colonoscopy is considered the criterion standard for detecting colorectal cancer; adequate prepar... more Colonoscopy is considered the criterion standard for detecting colorectal cancer; adequate preparation is crucial for an effective colonoscopy, but definitive data on the optimal preparation are lacking. Our aim was to assess the efficacy of split-dose versus non-split-dose preparations, the rate of adequate preparation according to type and dose of laxatives, the role of "runway time" (the interval time between the last drink of purgative and the beginning of colonoscopy), and to evaluate compliance as an additive risk factor for colon cleansing. A series of meta-analyses of controlled studies. Randomized clinical trial of split dose regimen versus entire dose taken on the day preceding colonoscopy. Published trials (1960-2013) comparing split-dose versus non-split-dose preparations in adults undergoing colonoscopy were selected by using MEDLINE, the Cochrane Central Register of Controlled Trials, clinicaltrial.gov, ISI Web of Science, and Scopus. Colonoscopy. Rate difference of the degree of colon cleansing between split dose and whole dose was the primary measure of treatment effect. We included 29 studies. Overall, an adequate preparation was obtained in 85% of patients in the split-dose group and in 63% of the non-split-dose group (rate difference 22%). The heterogeneity was caused by 5 factors: the runway time (the longer, the worse the cleansing), type of diet, male sex, use of polyethylene glycol 4 L, and the Jadad score. Compliance was significantly higher in the split-dose group. Average quality of the included studies and publication bias. We provided further evidence of the superiority of a split-dose regimen over a non-split-dose regimen and showed that, regardless of type and dose, the superiority of split-dose regimens remains valid if the "golden 5 hours" rule is preserved.
Current guidelines recommend endoscopy for dyspeptic patients &am... more Current guidelines recommend endoscopy for dyspeptic patients >45 yr of age and/or with "alarm" symptoms. The management of younger patients with uncomplicated dyspepsia is controversial. The objective of the study was to identify any risk factors predictive of upper gastrointestinal malignancy in patients with uncomplicated dyspepsia and validate their ability in refining indications for endoscopy. Prospective database study of consecutive uninvestigated dyspeptic outpatients undergoing endoscopy was performed. A questionnaire including multiple possible prognostic variables was systematically submitted to patients prior to endoscopic examination. Risk factors for upper gastrointestinal malignancy identified were used to derive a prediction rule subsequently validated on an independent population. A total of 5,224 patients with uncomplicated dyspepsia were considered (training sample). Twenty-two (16 males) had malignancy at endoscopy. These patients were about 20 yr older than patients with no malignancy (p < 0.001). The mean age of females with cancer was almost 10 yr higher compared to males (p= 0.08). Such differences in age were confirmed in a split sample of 3,684 patients (p < 0.001 and p < 0.05, respectively). The age cut-offs identified were 35 yr for males and 56 yr for females. The age threshold for endoscopy should be lowered in males to decrease the risk of missing cancers, and can be safely increased in females without affecting outcomes. In patients with uncomplicated dyspepsia, the combination of age and gender provides a better discriminant power than age alone.
Background Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although... more Background Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although highly eff ective, the standard sequential therapy fails in a certain number of patients. Moreover, the cure rate following a levofl oxacin-amoxicillin second-line triple therapy seems to be decreasing. We tested the effi cacy of modifi ed 10-day sequential therapy, and an intensifi ed levofl oxacin-amoxicillin regimen as fi rst-and second-line therapy respectively.
Recent studies have shown adjuvant properties of baculovirus by enhancing and modulating the immu... more Recent studies have shown adjuvant properties of baculovirus by enhancing and modulating the immune response in mammals. This ability has been explained in part by the activation of the innate immunity. In addition, baculovirus induce a vigorous cytotoxic response characterized by a large number of IFNγ-producing cells. By flow cytometry analysis, we demonstrated that, when inoculated in mice, wild type
Integrity of p27-p55 operon has been demonstrated to be crucial for replication of Mycobacterium ... more Integrity of p27-p55 operon has been demonstrated to be crucial for replication of Mycobacterium tuberculosis, the main agent of human tuberculosis, in the mouse model of infection. However, the individual contribution of each gene of the operon for the virulence of pathogenic Mycobacterium spp. still remains unclear. The operon is formed by two genes, p27 and p55. p27 gene encodes a lipoprotein that binds triacylated glycolipids and modulates the host immune responses by inhibiting the MHC-II Ag processing. Besides, p55 encodes an efflux pump that, together with P27, is involved in resistance to drugs. In this study, we evaluated the individual contribution of P27 and P55 to the virulence of Mycobacterium bovis, the etiological agent for bovine tuberculosis. Knockout mutation of p27-p55 operon in M. bovis severely decreased the virulence of the bacteria when assessed in a progressive model of pulmonary tuberculosis in Balb/c mice. In addition, the mutant strain showed poor replicat...
Live vaccine mce s u m m a r y A Mycobacterium bovis strain deleted in mce2A and mce2B genes (M. ... more Live vaccine mce s u m m a r y A Mycobacterium bovis strain deleted in mce2A and mce2B genes (M. bovis Dmce2) was tested as an experimental vaccine in cattle challenged with a virulent M. bovis strain. Three-and-a-half-month old calves (n ¼ 5 to 6 per group) were vaccinated and challenged with a virulent strain of M. bovis by the intratracheal route 9 weeks after vaccination. A non-vaccinated group and a group vaccinated with BCG were included as controls. Blood samples were collected to measure IFN-g by an interferon-gamma release assay (IGRA), cytometry and cytokine responses of bovine purified protein derivative (PPD) restimulated peripheral blood mononuclear cells (PBMCs). The IGRA test showed IFN-g values similar to pre-vaccination except for the animals vaccinated with M. bovis Dmce2, where a significant increase was observed at 30 days post-vaccination. The expression of IL-2R on CD4 þ cells in response to PPD from the animals vaccinated with Dmce2 increased at 15 days post-vaccination compared to cells from nonvaccinated group. Vaccination of cattle with M. bovis Dmce2 induced the highest (P < 0.05) expression of IFN-g and IL-17 mRNA upon PPD stimulation of PBMCs compared to vaccination with BCG or that for the non-vaccinated group. There was a weak positive correlation between the production of these proinflammatory cytokines post-vaccination and reduced pathology scores post-challenge. The animals were euthanized and necropsied 100 days after challenge. The group vaccinated with M. bovis Dmce2 displayed a significantly lower histopathological score for lesions in lungs and pulmonary lymph nodes than for the other groups (P < 0.05). A marked positive reaction to tuberculin intradermal test was observed post-vaccination in animals vaccinated with M. bovis Dmce2 compared to those vaccinated with BCG or the non-vaccinated group. In contrast, after challenge, non-vaccinated animals had greater skin test responses than the vaccinated animals. In summary, M. bovis Dmce2 is a promising vaccine candidate to control M. bovis pathogenesis in cattle.
A Mycobacterium bovis knockout in p27-p55 operon was tested as an antituberculosis experimental v... more A Mycobacterium bovis knockout in p27-p55 operon was tested as an antituberculosis experimental vaccine in animal models. The mutant MbΔp27-p55 was significantly more attenuated in nude mice than its parental strain but more virulent than BCG Pasteur. Challenge experiments in mice and guinea pigs using M. bovis or M. tuberculosis strains showed similar protection conferred by MbΔp27-p55 mutant than BCG in terms of pathology and bacterial loads in spleen but lower protection than BCG in lungs. When tested in cattle, MbΔp27-p55 did not induce IL-2 expression and induced a very low production of IFNγ, suggesting that the lack of P27/P55 reduces the capacity of M. bovis of triggering an adequate Th1 response.
In this study, a Mycobacterium bovis knockout strain in phoP-phoR and mce2 operons was tested as ... more In this study, a Mycobacterium bovis knockout strain in phoP-phoR and mce2 operons was tested as an antituberculosis experimental vaccine in animal models. The double mutant strain was significantly more attenuated than the wild type strain in inmunocompetent and inmunodeficient mice. Vaccination with the double mutant protected mice against challenge with a virulent M. bovis strain.
Some intracellular bacteria are known to cause long-term infections that last decades without com... more Some intracellular bacteria are known to cause long-term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long-term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re-infection and also with the specific expression of stress-and survivalrelated genes. Our findings identify bacterial traits implicated in the establishment of long-term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments.
The limited efficacy of the BCG vaccine for tuberculosis, coupled with emerging information sugge... more The limited efficacy of the BCG vaccine for tuberculosis, coupled with emerging information suggesting that it is poorly protective against newly emerging strains of Mycobacterium tuberculosis such as the W-Beijing isolates, makes it paramount to search for more potent alternatives. One such class of candidates is attenuated mutants derived from M. tuberculosis itself. We demonstrate here, in an initial short term assay, that mutants derived from disruption of the mce genes of the bacillus were highly protective in guinea pigs exposed by low dose aerosol infection with the virulent W-Beijing isolate SA161. This protection was demonstrated by a significant reduction in the numbers of bacilli harvested from the lungs, and dramatic improvements in lung histopathology.
Tuberculosis is still one of the main challenges to human global health, leading to about two mil... more Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine Mycobacterium bovis BCG. In this article, we analyze the potential use of an attenuated mutant of Mycobacterium tuberculosis H37Rv lacking the sigma factor E as a live vaccine. We have demonstrated that BALB/c mice infected by the intratracheal route with this mutant strain showed significantly higher survival rates and less tissue damage than animals infected with the parental or complemented mutant strain. Although animals infected with the sigE mutant had low bacillary loads, their lungs showed significantly higher production of the protective factors gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), inducible nitric oxide synthase (iNOS), and -defensins than those of animals infected with the parental or complemented mutant strain. Moreover, we demonstrate that the sigE mutant, when inoculated subcutaneously, was more attenuated than BCG in immunodeficient nude mice, thus representing a good candidate for a novel attenuated live vaccine strain. Finally, when we used the sigE mutant as a subcutaneous vaccine, it was able to induce a higher level of protection than did BCG with both H37Rv and a highly virulent strain of M. tuberculosis (Beijing code 9501000). Taken together, our findings suggest that the sigE mutant is a very promising strain for the development of a new vaccine against tuberculosis.
The identification of bovine tuberculosis (bTB) biomarkers in specific stages of the disease will... more The identification of bovine tuberculosis (bTB) biomarkers in specific stages of the disease will contribute to a better understanding of the immunopathology associated with tuberculosis and to improve the disease diagnosis and prognosis. The aim of this study was to understand the changing profile of the immune responses during the course of infection and to identify biomarkers associated with pathology. Here we describe the immune response developed in experimentally infected cattle with field Mycobacterium bovis strains. Blood samples were taken from each animal at different time points after M. bovis intratracheal infection and lymphocyte subset activation and cytokine mRNA expression were determined from peripheral blood mononuclear cells in response to purified protein derivative (PPDB). We found that CD4 and CD8 activation during the early stages of infection, together with IL-17 gene expression, were positively associated with pathology. The results of this study provide evidences of the role of IL-17 in the immunopathology of tuberculosis and support the use of IL-17 as a potential biomarker with predictive value of prognosis in bTB.
Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex,... more Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 M. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide.
Social Psychiatry and Psychiatric Epidemiology, 2006
j Abstract Aim This cross-sectional study attempted to identify factors associated with clinician... more j Abstract Aim This cross-sectional study attempted to identify factors associated with clinicians' dispositions of patients after the first visit in an outpatient psychiatric department. Methods Over a 33month period, all new episodes of care with the department were included in the study. For each patient, socio-demographic, clinical information and contact characteristics were prospectively collected in relation to the first visit, as was information on case disposition. Factors associated with clinicians' disposition were analysed. Results Of the 1,138 patients who met the study criteria, 848 (75%) were followed up by the department, 150 (13%) were referred to other services and 140 (12%) were discharged. Suffering from a major psychiatric disorder, being younger and not living in an institution influenced clinicians' disposition to follow-up patients. Older age increased the chances of being referred to other services rather than discharged. Conclusions Examining decision-making behaviour in out-patient psychiatric departments is a worthwhile endeavour because this setting represents the main entry point of modern and accessible community-based systems of care. The findings confirmed the importance of psychiatric determinants in the dispositional process and contribute to make clinicians more aware of other factors related to their decision-making.
We evaluate the effect of two different dialdehydic compounds on neuropathic pain. Sciatic spared... more We evaluate the effect of two different dialdehydic compounds on neuropathic pain. Sciatic spared nerve injury and paclitaxel evoked painful peripheral neuropathy. We investigate the allodynic and hyperalgesic neuropathic behaviour. We analyse the reactive macro and microgliosis by GFAP and Iba1 labeling. We hypothesize a general property of dialdehydes as analgesic and anti-gliotic molecules.
Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactor... more Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing. To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations. Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed. Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02-1.43] and 1.27 [1.05-1.53]), diabetes mellitus (odds ratio, 2.35 [1.68-3.29] and 2.12 [1.47-3.05]), chronic constipation (odds ratio, 1.60 [1.30-1.97] and 1.55 [1.23-1.94]), incomplete purge intake (odds ratio, 2.36 [1.90-2.94] and 2.11 [1.68-2.65]) and a runway time &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;12h (odds ratio, 3.36 [2.40-4.72] and 2.53 [1.74-3.67]). We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients.
In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroente... more In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, Jan 14, 2015
Serrated lesions are recognized as important contributors to colorectal cancer incidence. We aime... more Serrated lesions are recognized as important contributors to colorectal cancer incidence. We aimed to prospectively assess the prevalence of serrated lesions and identify potential predictors of these lesions during colonoscopy in an Italian population. Prospective cross sectional study involving 8 endoscopy units from February 1st to July 31st 2012. Out of 2468 colonoscopies, 886 precancerous lesions were detected in 567 patients. Of these, 173 SELs were diagnosed in 148 patients (140 serrated/hyperplastic polyps and 33 serrated adenomas). Prevalence was 7% (173/2468). Serrated lesions accounted for 19.5% of all precancerous lesions. Serrated polyps were prevalent in the left colon (42.1%) and serrated adenomas in the proximal colon (54.5%). Independent clinical predictors of serrated lesions were patient age (OR 0.98 [0.97-1.00]) and post-polypectomy surveillance (OR 1.87 [1.24-2.82]). Endoscopic predictors were right colon location (OR 2.65 [1.63-4.30] vs. rectum; and 1.53 [1.03-...
Endoscopic treatment with combined modalities is considered standard of care for patients with hi... more Endoscopic treatment with combined modalities is considered standard of care for patients with high-risk peptic ulcer bleeding. This study compared epinephrine injection plus bipolar probe coagulation with bipolar probe coagulation alone in patients with high-risk peptic ulcer bleeding. Patients with endoscopically confirmed peptic ulcer bleeding (active or visible vessel) seen from January 2000 through December 2002 were prospectively randomized to two groups. The study group (n = 58) had epinephrine injection followed by bipolar coagulation; the control group (n = 56) was treated by bipolar coagulation alone. The primary outcomes assessed were the rate of initial hemostasis and the rate of recurrent bleeding. Secondary outcomes were the following: need for surgical intervention to control bleeding, transfusion requirements, length of hospital stay (in days), and 30-day mortality. The rate of initial hemostasis was significantly higher in the combination therapy group ( p = 0.02; a...
The role of glial cells to the pathogenesis and maintenance of persistent pain is largely recogni... more The role of glial cells to the pathogenesis and maintenance of persistent pain is largely recognized but yet poorly elucidated. Mechanisms linking reactive gliosis to neuropathic pain are just emerging, reshaping the current understanding of pain circuitry and sensory processing. This process involves the activation of glial cells, resulting in the reactive gliosis, that in turn facilitates the release of pro-nociceptive mediators (e.g. ATP, glutamate, cytokines) that activate and sensitize spinal dorsal horn neurons. Evidence from a variety of experimental models indicated the activation of ATP purinergic P2X receptor subtypes, including P2X7, mostly expressed on glial cells, as a mechanism modulating pain perception, suggesting that purinergic neuro-glial interactions are important modulators of sensory neurotransmission. In this study, we used the sciatic spared nerve injury (SNI) model of neuropathic pain in rats as a tool to induce reactive gliosis in the dorsal horn of lumbar ...
Colonoscopy is considered the criterion standard for detecting colorectal cancer; adequate prepar... more Colonoscopy is considered the criterion standard for detecting colorectal cancer; adequate preparation is crucial for an effective colonoscopy, but definitive data on the optimal preparation are lacking. Our aim was to assess the efficacy of split-dose versus non-split-dose preparations, the rate of adequate preparation according to type and dose of laxatives, the role of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;runway time&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (the interval time between the last drink of purgative and the beginning of colonoscopy), and to evaluate compliance as an additive risk factor for colon cleansing. A series of meta-analyses of controlled studies. Randomized clinical trial of split dose regimen versus entire dose taken on the day preceding colonoscopy. Published trials (1960-2013) comparing split-dose versus non-split-dose preparations in adults undergoing colonoscopy were selected by using MEDLINE, the Cochrane Central Register of Controlled Trials, clinicaltrial.gov, ISI Web of Science, and Scopus. Colonoscopy. Rate difference of the degree of colon cleansing between split dose and whole dose was the primary measure of treatment effect. We included 29 studies. Overall, an adequate preparation was obtained in 85% of patients in the split-dose group and in 63% of the non-split-dose group (rate difference 22%). The heterogeneity was caused by 5 factors: the runway time (the longer, the worse the cleansing), type of diet, male sex, use of polyethylene glycol 4 L, and the Jadad score. Compliance was significantly higher in the split-dose group. Average quality of the included studies and publication bias. We provided further evidence of the superiority of a split-dose regimen over a non-split-dose regimen and showed that, regardless of type and dose, the superiority of split-dose regimens remains valid if the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;golden 5 hours&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; rule is preserved.
Current guidelines recommend endoscopy for dyspeptic patients &amp;amp;amp;amp;amp;amp;amp;am... more Current guidelines recommend endoscopy for dyspeptic patients &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;45 yr of age and/or with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;alarm&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; symptoms. The management of younger patients with uncomplicated dyspepsia is controversial. The objective of the study was to identify any risk factors predictive of upper gastrointestinal malignancy in patients with uncomplicated dyspepsia and validate their ability in refining indications for endoscopy. Prospective database study of consecutive uninvestigated dyspeptic outpatients undergoing endoscopy was performed. A questionnaire including multiple possible prognostic variables was systematically submitted to patients prior to endoscopic examination. Risk factors for upper gastrointestinal malignancy identified were used to derive a prediction rule subsequently validated on an independent population. A total of 5,224 patients with uncomplicated dyspepsia were considered (training sample). Twenty-two (16 males) had malignancy at endoscopy. These patients were about 20 yr older than patients with no malignancy (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The mean age of females with cancer was almost 10 yr higher compared to males (p= 0.08). Such differences in age were confirmed in a split sample of 3,684 patients (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 and p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, respectively). The age cut-offs identified were 35 yr for males and 56 yr for females. The age threshold for endoscopy should be lowered in males to decrease the risk of missing cancers, and can be safely increased in females without affecting outcomes. In patients with uncomplicated dyspepsia, the combination of age and gender provides a better discriminant power than age alone.
Background Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although... more Background Helicobacter pylori (H. pylori) treatment remains a challenge for physicians. Although highly eff ective, the standard sequential therapy fails in a certain number of patients. Moreover, the cure rate following a levofl oxacin-amoxicillin second-line triple therapy seems to be decreasing. We tested the effi cacy of modifi ed 10-day sequential therapy, and an intensifi ed levofl oxacin-amoxicillin regimen as fi rst-and second-line therapy respectively.
Recent studies have shown adjuvant properties of baculovirus by enhancing and modulating the immu... more Recent studies have shown adjuvant properties of baculovirus by enhancing and modulating the immune response in mammals. This ability has been explained in part by the activation of the innate immunity. In addition, baculovirus induce a vigorous cytotoxic response characterized by a large number of IFNγ-producing cells. By flow cytometry analysis, we demonstrated that, when inoculated in mice, wild type
Integrity of p27-p55 operon has been demonstrated to be crucial for replication of Mycobacterium ... more Integrity of p27-p55 operon has been demonstrated to be crucial for replication of Mycobacterium tuberculosis, the main agent of human tuberculosis, in the mouse model of infection. However, the individual contribution of each gene of the operon for the virulence of pathogenic Mycobacterium spp. still remains unclear. The operon is formed by two genes, p27 and p55. p27 gene encodes a lipoprotein that binds triacylated glycolipids and modulates the host immune responses by inhibiting the MHC-II Ag processing. Besides, p55 encodes an efflux pump that, together with P27, is involved in resistance to drugs. In this study, we evaluated the individual contribution of P27 and P55 to the virulence of Mycobacterium bovis, the etiological agent for bovine tuberculosis. Knockout mutation of p27-p55 operon in M. bovis severely decreased the virulence of the bacteria when assessed in a progressive model of pulmonary tuberculosis in Balb/c mice. In addition, the mutant strain showed poor replicat...
Live vaccine mce s u m m a r y A Mycobacterium bovis strain deleted in mce2A and mce2B genes (M. ... more Live vaccine mce s u m m a r y A Mycobacterium bovis strain deleted in mce2A and mce2B genes (M. bovis Dmce2) was tested as an experimental vaccine in cattle challenged with a virulent M. bovis strain. Three-and-a-half-month old calves (n ¼ 5 to 6 per group) were vaccinated and challenged with a virulent strain of M. bovis by the intratracheal route 9 weeks after vaccination. A non-vaccinated group and a group vaccinated with BCG were included as controls. Blood samples were collected to measure IFN-g by an interferon-gamma release assay (IGRA), cytometry and cytokine responses of bovine purified protein derivative (PPD) restimulated peripheral blood mononuclear cells (PBMCs). The IGRA test showed IFN-g values similar to pre-vaccination except for the animals vaccinated with M. bovis Dmce2, where a significant increase was observed at 30 days post-vaccination. The expression of IL-2R on CD4 þ cells in response to PPD from the animals vaccinated with Dmce2 increased at 15 days post-vaccination compared to cells from nonvaccinated group. Vaccination of cattle with M. bovis Dmce2 induced the highest (P < 0.05) expression of IFN-g and IL-17 mRNA upon PPD stimulation of PBMCs compared to vaccination with BCG or that for the non-vaccinated group. There was a weak positive correlation between the production of these proinflammatory cytokines post-vaccination and reduced pathology scores post-challenge. The animals were euthanized and necropsied 100 days after challenge. The group vaccinated with M. bovis Dmce2 displayed a significantly lower histopathological score for lesions in lungs and pulmonary lymph nodes than for the other groups (P < 0.05). A marked positive reaction to tuberculin intradermal test was observed post-vaccination in animals vaccinated with M. bovis Dmce2 compared to those vaccinated with BCG or the non-vaccinated group. In contrast, after challenge, non-vaccinated animals had greater skin test responses than the vaccinated animals. In summary, M. bovis Dmce2 is a promising vaccine candidate to control M. bovis pathogenesis in cattle.
A Mycobacterium bovis knockout in p27-p55 operon was tested as an antituberculosis experimental v... more A Mycobacterium bovis knockout in p27-p55 operon was tested as an antituberculosis experimental vaccine in animal models. The mutant MbΔp27-p55 was significantly more attenuated in nude mice than its parental strain but more virulent than BCG Pasteur. Challenge experiments in mice and guinea pigs using M. bovis or M. tuberculosis strains showed similar protection conferred by MbΔp27-p55 mutant than BCG in terms of pathology and bacterial loads in spleen but lower protection than BCG in lungs. When tested in cattle, MbΔp27-p55 did not induce IL-2 expression and induced a very low production of IFNγ, suggesting that the lack of P27/P55 reduces the capacity of M. bovis of triggering an adequate Th1 response.
In this study, a Mycobacterium bovis knockout strain in phoP-phoR and mce2 operons was tested as ... more In this study, a Mycobacterium bovis knockout strain in phoP-phoR and mce2 operons was tested as an antituberculosis experimental vaccine in animal models. The double mutant strain was significantly more attenuated than the wild type strain in inmunocompetent and inmunodeficient mice. Vaccination with the double mutant protected mice against challenge with a virulent M. bovis strain.
Some intracellular bacteria are known to cause long-term infections that last decades without com... more Some intracellular bacteria are known to cause long-term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long-term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re-infection and also with the specific expression of stress-and survivalrelated genes. Our findings identify bacterial traits implicated in the establishment of long-term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments.
The limited efficacy of the BCG vaccine for tuberculosis, coupled with emerging information sugge... more The limited efficacy of the BCG vaccine for tuberculosis, coupled with emerging information suggesting that it is poorly protective against newly emerging strains of Mycobacterium tuberculosis such as the W-Beijing isolates, makes it paramount to search for more potent alternatives. One such class of candidates is attenuated mutants derived from M. tuberculosis itself. We demonstrate here, in an initial short term assay, that mutants derived from disruption of the mce genes of the bacillus were highly protective in guinea pigs exposed by low dose aerosol infection with the virulent W-Beijing isolate SA161. This protection was demonstrated by a significant reduction in the numbers of bacilli harvested from the lungs, and dramatic improvements in lung histopathology.
Tuberculosis is still one of the main challenges to human global health, leading to about two mil... more Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine Mycobacterium bovis BCG. In this article, we analyze the potential use of an attenuated mutant of Mycobacterium tuberculosis H37Rv lacking the sigma factor E as a live vaccine. We have demonstrated that BALB/c mice infected by the intratracheal route with this mutant strain showed significantly higher survival rates and less tissue damage than animals infected with the parental or complemented mutant strain. Although animals infected with the sigE mutant had low bacillary loads, their lungs showed significantly higher production of the protective factors gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), inducible nitric oxide synthase (iNOS), and -defensins than those of animals infected with the parental or complemented mutant strain. Moreover, we demonstrate that the sigE mutant, when inoculated subcutaneously, was more attenuated than BCG in immunodeficient nude mice, thus representing a good candidate for a novel attenuated live vaccine strain. Finally, when we used the sigE mutant as a subcutaneous vaccine, it was able to induce a higher level of protection than did BCG with both H37Rv and a highly virulent strain of M. tuberculosis (Beijing code 9501000). Taken together, our findings suggest that the sigE mutant is a very promising strain for the development of a new vaccine against tuberculosis.
The identification of bovine tuberculosis (bTB) biomarkers in specific stages of the disease will... more The identification of bovine tuberculosis (bTB) biomarkers in specific stages of the disease will contribute to a better understanding of the immunopathology associated with tuberculosis and to improve the disease diagnosis and prognosis. The aim of this study was to understand the changing profile of the immune responses during the course of infection and to identify biomarkers associated with pathology. Here we describe the immune response developed in experimentally infected cattle with field Mycobacterium bovis strains. Blood samples were taken from each animal at different time points after M. bovis intratracheal infection and lymphocyte subset activation and cytokine mRNA expression were determined from peripheral blood mononuclear cells in response to purified protein derivative (PPDB). We found that CD4 and CD8 activation during the early stages of infection, together with IL-17 gene expression, were positively associated with pathology. The results of this study provide evidences of the role of IL-17 in the immunopathology of tuberculosis and support the use of IL-17 as a potential biomarker with predictive value of prognosis in bTB.
Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex,... more Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 M. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide.
Social Psychiatry and Psychiatric Epidemiology, 2006
j Abstract Aim This cross-sectional study attempted to identify factors associated with clinician... more j Abstract Aim This cross-sectional study attempted to identify factors associated with clinicians' dispositions of patients after the first visit in an outpatient psychiatric department. Methods Over a 33month period, all new episodes of care with the department were included in the study. For each patient, socio-demographic, clinical information and contact characteristics were prospectively collected in relation to the first visit, as was information on case disposition. Factors associated with clinicians' disposition were analysed. Results Of the 1,138 patients who met the study criteria, 848 (75%) were followed up by the department, 150 (13%) were referred to other services and 140 (12%) were discharged. Suffering from a major psychiatric disorder, being younger and not living in an institution influenced clinicians' disposition to follow-up patients. Older age increased the chances of being referred to other services rather than discharged. Conclusions Examining decision-making behaviour in out-patient psychiatric departments is a worthwhile endeavour because this setting represents the main entry point of modern and accessible community-based systems of care. The findings confirmed the importance of psychiatric determinants in the dispositional process and contribute to make clinicians more aware of other factors related to their decision-making.
We evaluate the effect of two different dialdehydic compounds on neuropathic pain. Sciatic spared... more We evaluate the effect of two different dialdehydic compounds on neuropathic pain. Sciatic spared nerve injury and paclitaxel evoked painful peripheral neuropathy. We investigate the allodynic and hyperalgesic neuropathic behaviour. We analyse the reactive macro and microgliosis by GFAP and Iba1 labeling. We hypothesize a general property of dialdehydes as analgesic and anti-gliotic molecules.
Uploads
Papers by Maria Bianco