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1How antibiotic resistances could change Helicobacter pylori treatment:A matter of geography?显示文摘Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the administration of several consecutive standard therapies.Although antibiotic resistance reports describe alarming results,the outcome of therapeutic regimens does not seem to parallel this scenario in most cases,since a successful performance is often reached in more than 80%of cases.However,the phenomenon of increasing antibiotic resistance is being closely studied,and the results show controversial aspects even in the same geographic area.For the continents of Europe,America,Asia,Africa,and Oceania,minimal and maximal values of resistance to the main antibiotics(clarithromycin,amoxicillin,metronidazole,and levofloxacin)feature wide ranges in different countries.The real enigma is therefore linked to the several different therapeutic regimens,which show results that often do not parallel the in vitro findings even in the same areas.A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts.Moreover,not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome.The additional use of probiotics may help to reduce adverse events,but their therapeutic impact is doubtful.In conclusion,the'ideal therapy',paradoxically,appears to be a'utopia',despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H.pylori.The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide.On these bases,one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances.In this context,geography must be considered a relevant matter.Enzo Ierardi Floriana Giorgio Giuseppe Losurdo Alfredo Di Leo Mariabeatrice Principi 2013World Journal of Gastroenterology2013,19,45:23
2Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease?显示文摘Inflammatory bowel diseases(IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota(i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in theliterature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.Roberto Bringiotti Enzo Ierardi Rosa Lovero Giuseppe Losurdo Alfredo Di Leo Mariabeatrice Principi 2014World Journal of Gastrointestinal Pathophysiology2014,5,4:20
3Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis显示文摘AIM To define probiotic monotherapy effect on Helicobacter pylori(H. pylori) status by performing a systematic review.METHODS Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching Pub Med, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios(ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo.RESULTS Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14%(95%CI: 2%-25%, P =0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16%(95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12%(95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14%(95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics(95%CI: 2.97-21.05, P < 0.001). Probiotics induced a mean reduction in delta values higher than placebo(8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo(OR = 1, 95%CI: 0.06-18.08).CONCLUSION Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.Giuseppe Losurdo Rossella Cubisino Michele Barone Mariabeatrice Principi Gioacchino Leandro Enzo Ierardi Alfredo Di Leo 2018World Journal of Gastroenterology2018,24,1:18
4Optimizing proton pump inhibitors in Helicobacter pylori treatment:Old and new tricks to improve effectiveness显示文摘The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to antibiotics.On these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be administered.Therefore,several tricks need to be used to optimize eradication rate of different regimens.The administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is discouraged.However,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic variables.Finally,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic effect.However current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.Enzo Ierardi Giuseppe Losurdo Rosa Federica La Fortezza Mariabeatrice Principi Michele Barone Alfredo Di Leo 2019World Journal of Gastroenterology2019,25,34:15
5主要 clarithromycin 抵抗到 Helicobacter pylori : 这是为三倍的治疗失败的主要原因?显示文摘 Conventional triple therapies for Helicobacter pylori (H. pylori ) eradication have recently shown a disappointing reduction in effectiveness in many countries. The main reason for failure was found to be bacterial resistance to one of the most commonly used antibiotics, clarithromycin. An additional problem for conventional triple therapy is the high rate of resistance to metronidazole found in Europe, America and Asia. In Italy, in the last 15 years a 2-fold increase in resistance has occurred. A recent study of the whole of Italy included about 20 patients from each region at the first endoscopic diagnosis of H. pylori infection. The most surprising result was the patchy distribution of resistance, which was almost absent in two regions (one northern and one southern), although the highest prevalence was found in some regions of the South. In the paediatricpopulation we found a 25% prevalence of resistance in a sample of H. pylori positive children observed between 2002 and 2007, mirroring data obtained in southern European countries. Clarithromycin resistance assessment is currently based on phenotypic detection performed after culture the agar dilution method or E-test, and genotypic methods based on polymerase chain reaction (PCR). In a recent comparative study we found a 71.2% agreement between the two methods. Culture-free techniques are highly accurate in finding even minimal traces of genotypically resistant strains. Moreover, PCR-based tools are accurate in detecting a heteroresistant status, defined as the co-existence of some strains that are susceptible and some resistant to the same antibiotic in an individual patient. Three point mutations, namely A2143G , A2142G and A2142C , are responsible for 90% of cases of primary clarithromycin resistance in H. pylori strains isolated in Western countries, although we previously demonstrated that the presence of the A2143G mutation, but not A2142G or A2142C , significantly lowered the H. pylori eradication rate. Treatment failure has considerable cost/benefit implications because of 'waste' of National Health System and patient resources, in terms of drugs, further diagnostic tests and medical examination expenses. Therefore, in future it would be very useful to be able to test for clarithromycin resistance before starting conventional triple therapy. Hopefully, fast, effective noninvasive tests may soon be devised to determine this condition.Floriana Giorgio Mariabeatrice Principi Vincenzo De Francesco Angelo Zullo Giuseppe Losurdo Alfredo Di Leo Enzo Ierardi 2013World Journal of Gastrointestinal Pathophysiology2013,4,3:10
6Inpatient capsule endoscopy leads to frequent incomplete small bowel examinations显示文摘AIM:To examine the predictive factors of capsule endoscopy(CE) completion rate(CECR) including the effect of inpatient and outpatient status.METHODS:We identified 355 consecutive patients who completed CE at Rush University Medical Center between March 2003 and October 2005.Subjects for CE had either nothing by mouth or clear liquids for the afternoon and evening of the day before the procedure.CE exams were reviewed by two physicians who were unaware of the study hypotheses.After retrospective analysis,21 cases were excluded due to capsule malfunction,prior gastric surgery,endoscopic capsule placement or insufficient data.Of the remaining 334 exams [264 out-patient(OP),70 in-patient(IP)],CE indications,findings,location of the patients [IP vs OP and intensive care unit(ICU) vs general medical floor(GMF)] and gastrointestinal transit times were analyzed.Statistical analysis was completed using SPSS version 17(Chicago,IL).Chi-square,t test or fisher exact-tests were used as appropriate.Multivariate logistic regression analysis was used to identify variables associated with incomplete CE exams.RESULTS:The mean age for the entire study population was 54.7 years.Sixty-one percent of the study population was female,and gender was not different between IPs vs OPs(P = 0.07).The overall incomplete CECR was 14% in our study.Overt obscure gastrointestinal bleeding(OGB) was a significantly more common indication for the IP CE(P = 0.0001),while abdominal pain and assessment of IBD were more frequent indications for the OP CE exams(P = 0.002 and P = 0.01,respectively).Occult OGB was the most common indication and arteriovenous malformations were the most common finding both in the IPs and OPs.The capsule did not enter the small bowel(SB) in 6/70 IPs and 8/264 OPs(P = 0.04).The capsule never reached the cecum in 31.4%(22/70) of IP vs 9.5%(25/264) of OP examinations(P < 0.001).The mean gastric transit time(GTT) was delayed in IPs compared to OPs,98.5 ± 139.5 min vs 60.4 ± 92.6 min(P = 0.008).Minimal SB transit time was significantly prolonged in the IP compared to the OP setting [IP = 275.1 ±111.6 min vs OP = 244.0 ± 104.3 min(P = 0.037)].CECR was also significantly higher in the subgroup of patients with OGB who had OP vs IP exams(95% vs 80% respectively,P = 0.001).The proportion of patients with incomplete exams was higher in the ICU(n = 7/13,54%) as compared to the GMF(n = 15/57,26%)(P = 0.05).There was only a single permanent SB retention case which was secondary to a previously unknown SB stricture,and the remaining incomplete SB exams were due to slow transit.Medications which affect gastrointestinal system motility were tested both individually and also in aggregate in univariate analysis in hospitalized patients(ICU and GMF) and were not predictive of incomplete capsule passage(P > 0.05).Patient location(IP vs OP) and GTT were independent predictors of incomplete CE exams(P < 0.001 and P = 0.008,respectively).CONCLUSION:Incomplete CE is a multifactorial problem.Patient location and related factors such as severity of illness and sedentary status may contribute to incomplete exams.Cemal Yazici John Losurdo Michael D Brown Scott Oosterveen Robert Rahimi Ali Keshavarzian Leila Bozorgnia Ece Mutlu 2012World Journal of Gastroenterology2012,18,36:6
7Ulcerative colitis: From inflammation to cancer. Do estrogen receptors have a role?显示文摘Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors(extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogenreceptors(ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anticarcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.Mariabeatrice Principi Michele Barone Maria Pricci Nicola De Tullio Giuseppe Losurdo Enzo Ierardi Alfredo Di Leo 2014World Journal of Gastroenterology2014,20,33:4
8Noninvasive molecular analysis of Helicobacter pylori : Is it time for tailored first-line therapy?显示文摘The main problem of Helicobacter pylori(H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction(PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.Enzo Ierardi Floriana Giorgio Andrea Iannone Giuseppe Losurdo Mariabeatrice Principi Michele Barone Antonio Pisani Alfredo Di Leo 2017World Journal of Gastroenterology2017,23,14:3
9Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up显示文摘AIM: To assess the evolution of duodenal lymphocytosis(DL), a condition characterized by increased intraepithelial lymphocytes(IELs), over 2 years of follow-up.METHODS: Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease(CD) were included. Evaluation of IELs infiltrate in duodenal biopsy sampleswas carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: Ig G and Ig A anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance i m a g i n g w e r e p e r f o r m e d w h e n n e c e s s a r y. R i s k factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR.RESULTS: Eighty-five patients(16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed Ig G anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity(GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn's disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25(OR = 1640.4) or 15-25(OR = 16.95), human leukocyte antigen(HLA) DQ2/8(OR = 140.85) or DQA1*0501(OR = 15.36), diarrhea(OR = 5.56) and weakness(OR = 11.57). GS was associated with IELs 15-25(OR = 28.59), autoimmune thyroiditis(OR = 87.63), folate deficiency(OR = 48.53) and diarrhea(OR = 54.87).CONCLUSION: DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS.Giuseppe Losurdo Domenico Piscitelli Antonio Giangaspero Mariabeatrice Principi Francesca Buffelli Floriana Giorgio Lucia Montenegro Claudia Sorrentino Annacinzia Amoruso Enzo Ierardi Alfredo Di Leo 2015World Journal of Gastroenterology2015,21,24:2
10Hepatitis B vaccination in patients with inflammatory bowel disease显示文摘AIM:To determine the prevalence for hepatitis B virus(HBV) and HBV screening and vaccination practices for inflammatory bowel disease(IBD).METHODS:This study is a retrospective,cross-sectional observational study.A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section.The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic,and that they had a diagnosis of IBD at the time of visit discharge.Once identified,each record was analyzed to determine whether the subject had been infected with HBV in the past,already been vaccinated against HBV,or advised to get vaccinated and followed through with the recommended vaccination.RESULTS:About 254 out of 500 patients(51%) had HBV screening ordered.Among those ordered to have screening tests,86% followed through with HBV serology.Gastroenterology physicians had significantly different screening ratios from each other(P < 0.001).There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians(0.505 ± 0.023 vs 0.536 ± 0.066,P = 0.66).Of those 220 patients screened,51% of IBD patients were found not to be immune against HBV.Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV.IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians(0.168 ± 0.019 vs 0.038 ± 0.026,P = 0.015).Present and/or past HBV infection was found in 3.6% of the patients who had serology checked.There was no statistically significant difference in the prevalence of hepatitis B surface antigen(HBsAg) between our study and that reported in previous studies done in Spain(4/220 vs 14/2076 respectively,P = 0.070); and in France(4/220 vs 3/315 respectively,P = 0.159).But,the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain(7/220 vs 155/2076 respectively,P = 0.006); and was not sig-nificantly different from that reported in the study in France(7/220 vs 8/315 respectively,P = 0.313).CONCLUSION:The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies.Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.Ruwaida Ben Musa Anuhya Gampa Sanjib Basu Ali Keshavarzian Garth Swanson Michael Brown Rana Abraham Keith Bruninga John Losurdo Mark DeMeo Sohrab Mobarhan David Shapiro Ece Mutlu 2014World Journal of Gastroenterology2014,20,41:2
11Novel frontiers of agents for bowel cleansing for colonoscopy显示文摘The incidence of colorectal cancer(CRC)is characterized by rapid declines in the wake of widespread screening.Colonoscopy is the gold standard for CRC screening,but its accuracy is related to high quality of bowel preparation(BP).In this review,we aimed to summarized the current strategy to increase bowel cleansing before colonoscopy.Newly bowel cleansing agents were developed with the same efficacy of previous agent but requiring less amount of liquid to improve patients’acceptability.The role of the diet before colonoscopy was also changed,as well the contribution of educational intervention and the use of adjunctive drugs to improve patients’tolerance and/or quality of BP.The review also described BP in special situations,as lower gastrointestinal bleeding,elderly people,patients with chronic kidney disease,patients with inflammatory bowel disease,patients with congestive heart failure,inpatient,patient with previous bowel resection,pregnant/lactating patients.The review underlined the quality of BP should be described using a validate scale in colonoscopy report and it explored the available scales.Finally,the review explored the possible contribution of bowel cleansing in post-colonoscopy syndrome that can be related by a transient alteration of gut microbiota.Moreover,the study underlined several points needed to further investigations.Milena Di Leo Andrea Iannone Monica Arena Giuseppe Losurdo Maria Angela Palamara Giuseppe Iabichino Pierluigi Consolo Maria Rendina Carmelo Luigiano Alfredo Di Leo 2021World Journal of Gastroenterology2021,27,45:2
12Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm显示文摘Non celiac gluten sensitivity(NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease(CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders(irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.Giuseppe Losurdo Mariabeatrice Principi Andrea Iannone Annacinzia Amoruso Enzo Ierardi Alfredo Di Leo Michele Barone 2018World Journal of Gastroenterology2018,24,14:2
13Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma显示文摘BACKGROUND Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the antiangiogenic and anti-fibrogenic activity of these drugs. AIM To elucidate the role of ARBs and ACE-Is in HCC. METHODS We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms 'angiotensin-converting enzyme inhibitors' OR 'ACE inhibitors' OR 'ACE-I' AND 'hepatocarcinoma*' OR 'hepatocellular carcinoma;moreover 'angiotensin II type 1 receptor blockers' OR 'ARBs' AND 'hepatocarcinoma*' OR 'hepatocellular carcinoma'. Eligibility criteria were:(1) prospective or retrospective clinical studies;(2) epidemiological studies;and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals.RESULTS Thirty-one studies were selected. Three interventional studies showed that ACEIs had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. CONCLUSION In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations.Michele Barone Maria Teresa Viggiani Giuseppe Losurdo Mariabeatrice Principi Alfredo Di Leo 2019World Journal of Gastroenterology2019,25,20:2
14Intraepithelial lymphocytes: bystanders or causative factors in functional gastrointestinal disorders?显示文摘Intraepithelial lymphocytes(IELs)are immune cells located in the epithelium of the mucosal layer of the gastrointestinal tract that typically show a CD3-positive phenotype.They are T lymphocytes that are involved in the primary immune response to several luminal antigens,such as food proteins and infectious agents.For this reason,their increase may be pathogenetic in several diseases,the most important being celiac disease.However,an increase above 25 IELs/100 enterocytes in the duodenum,which is considered the cutoff value for celiac disease,may occur in several conditions,such as nonceliac gluten sensitivity,food allergy,Helicobacter pylori(H.pylori)infection,gastroenteritis,and even irritable bowel syndrome(IBS).Therefore,the generic term“microscopic enteritis”or“duodenal lymphocytosis”has been proposed for this condition.Giuseppe Losurdo Domenico Piscitelli Enzo Ierardi Alfredo Di Leo 2021Cellular & Molecular Immunology2021,18,7:2
15在煽动性的肠疾病的 Fibrogenesis 和纤维变性: 一样的硬币的好、坏的方面?显示文摘 Fibrogenesis in inflammatory bowel diseases is a complex phenomenon aimed at mucosal repair. However, it may provoke intestinal fibrosis with the development of strictures which require surgery. Therefore, fibrogenesis may be considered as a 'two-faced' process when related to chronic intestinal inflammation. Many types of cells may be converted into the fibrogenic phenotype at different levels of the intestinal wall. A complex interaction of cytokines, adhesion molecules and growth factors is involved in the process. We report an overview of recent advances in molecular mechanisms of stricturizing Crohn’s disease(CD) including the potential role of trasforming growth factor beta, protein kinase C and Ras, Raf and ERK proteins. Fibrotic growth factors such as vascular endothelial growth factor and platelet-derived growth factor, as well as the Endothelial-to-Mesenchymal Transition induced by transforming growth factor-β, are considered. Finally, our experience, focused on tumor necrosis factor α(the main cytokine of inflammatory bowel diseases) and the link between syndecan 1(a heparan sulphate adhesion molecule) and basic fibroblast growth factor(a strong stimulator of collagen synthesis) is described. We hypothesize a possible molecular pattern for mucosal healing as well as how its deregulation could be involved in fibrotic complications of CD. A final clinical point is the importance of performing an accurate evaluation of the presence of fibrotic strictures before starting anti-tumor necrosis α treatment, which could worsen the lesions.Mariabeatrice Principi Floriana Giorgio Giuseppe Losurdo Viviana Neve Antonella Contaldo Alfredo Di Leo Enzo Ierardi 2013World Journal of Gastrointestinal Pathophysiology2013,4,4:2
16Study of the tempreture-dependent interaction of 4H- SiC and 6H-SiC surfaces with atomic hydrogen 显示文摘Losurdo Maria Bruno Giovanni Brown April 2004Applied Physic Letter2004,84,20:1
17Modification of 4H-SiC and 6H-SiC(0001) surfaces through the interaction with atomic hydrogen and nitrogen显示文摘Losurdo M Giangregorio M M Capezzuto P 2005Journal of Electronic Materials2005,34,4:1
18Graphene CVD growth on copper and nickel: Role of hydrogen in kinetics and structure 显示文摘LOSURDO M GIANGREGORIO M M CAPEZZUTO P 2011Physical Chemistry Chemical Physics2011,13,20:1
19The stolen memory:a case of transient global amnesia显示文摘Morosetti R Losurdo A Testani E 2010Biological Psychiatry2010,67,:1
20Dynamics of low temperature PECVD growth of microcrystalline silicon thin films: Impact of substrate surface treatments 显示文摘Losurdo M Giangregorio M M Sacchetti A et ol 2006Journal of Non-Crystalline Solids2006,352,:1
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