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Intraepithelial lymphocytes: bystanders or causative factors in functional gastrointestinal disorders?

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Cellular & Molecular Immunology 2021年第7期18卷 1620-1621页

作者： giuseppe losurdo Domenico Piscitelli Enzo Ierardi Alfredo Di Leo Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBariItaly Ph.D.Course in Organs and Tissues Transplantation and Cellular Therapies Department of Emergency and Organ TransplantationUniversity of BariBariItaly Section of Pathology Department of Emergency and Organ TransplantationUniversity of BariBariItaly

Intraepithelial lymphocytes(IELs)are immune cells located in the epithelium of the mucosal layer of the gastrointestinal tract that typically show a CD3-positive *** are T lymphocytes that are involved in the primary immune response to several luminal antigens,such as food proteins and infectious *** this reason,their increase may be pathogenetic in several diseases,the most important being celiac ***,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(***)infection,gastroenteritis,and even irritable bowel syndrome(IBS).Therefore,the generic term“microscopic enteritis”or“duodenal lymphocytosis”has been proposed for this condition.

关键词： lymphocytes gastrointestinal epithelium

Unexpected me diastinal mass in a liver transplanted patient

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 199-201页

作者： giuseppe losurdo giuseppe Ingravallo Antonio Mongelli Nicola Maurizio Castellaneta Antonio Pisani Section of Gastroenterology Department of Emergency and Organ Transplantation University "Aldo Moro" Section of Pathology Department of Emergency and Organ Transplantation University "Aldo Moro"

To the Editor:The risk of de novo cancer increases by 2 to 7-fold after liver transplantation[1].The most common de novo cancers are both solid(non-melanoma skin cancers,colorectal carcinoma,genito-urinary and head-neck cancer)[2,3]as well as hematologic malignancies,in particular the so-called post-transplant lymphoproliferative disorder[4].

关键词： mediastinal mass liver transplanted patient post-transplant

Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第20期25卷 2524-2538页

作者： Michele Barone Maria Teresa Viggiani giuseppe losurdo Mariabeatrice Principi Alfredo Di Leo Gastroenterology Section Department of Emergency and Organ Transplantation University of Bari Aldo Moro

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 *** 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

关键词： Cirrhosis Renin Angiotensin Survival Cancer prevention Hepatocarcinoma

Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis

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World Journal of Gastroenterology 2018年第1期24卷 139-149页

作者： giuseppe losurdo Rossella Cubisino Michele Barone Mariabeatrice Principi Gioacchino Leandro Enzo Ierardi Alfredo Di Leo Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity "Aldo Moro"Piazza Giulio Cesare National Institute of Gastroenterology "S De Bellis" Research Hospital

AIM To define probiotic monotherapy effect on Helicobacter pylori(H. pylori) status by performing a systematic *** 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 *** 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.

关键词： Helicobacter pylori probiotics eradication meta-analysis breath test

Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm

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World Journal of Gastroenterology 2018年第14期24卷 1521-1530页

作者： giuseppe losurdo Mariabeatrice Principi Andrea Iannone Annacinzia Amoruso Enzo Ierardi Alfredo Di Leo Michele Barone Section of Gastroenterology Department of Emergency and Organ Transplantation University "Aldo Moro" of Bari

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

关键词： Non celiac gluten sensitivity celiac disease gluten gluten ataxia autoimmunity gluten-related disorders thyroiditis extra-intestinal

Optimizing proton pump inhibitors in Helicobacter pylori treatment:Old and new tricks to improve effectiveness

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World Journal of Gastroenterology 2019年第34期25卷 5097-5104页

作者： Enzo Ierardi giuseppe losurdo Rosa Federica La Fortezza Mariabeatrice Principi Michele Barone Alfredo Di Leo Section of Gastroenterology Department of Emergency and Organ Transplantation University of Bari

The survival and replication cycle of Helicobacter pylori(***)is strictly dependant on intragastric pH,since *** 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 *** these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be ***,several tricks need to be used to optimize eradication rate of different *** 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 ***,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 ***,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 *** 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.

关键词： Helicobacter pylori Proton pump inhibitors Eradication Cytochrome P450 Optimization

Role of concomitant therapy for Helicobacter pylori eradication: A technical note

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World Journal of Gastroenterology 2016年第38期22卷 8638-8640页

作者： giuseppe losurdo Floriana Giorgio Andrea Iannone Mariabeatrice Principi Michele Barone Alfredo Di Leo Enzo Ierardi Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of Bari

We read with interest the recent meta-analysis by Lin et al who evaluated the effectiveness of concomitant regimen for Helicobacter pylori(H. pylori) in Chinese regions. They found that 7-d concomitant regimen is undoubtedly superior to 7-d triple therapy(91.2% vs 77.9%, P < 0.0001). However, it is a common belief that a triple therapy lasting 7 d should be definitively removed from the clinical practice for its ineffectiveness. Only its prolongation to 14 d may give satisfactory success rate. Thus, the assessment of an old and outdated treatment versus a more recent and successful one does not seem to bring novel and useful information. Moreover, a 7-d duration has not been ascertained for concomitant regimen, as main guidelines recommend a 10-d schedule for this scheme. Therefore, only studies comparing 10-d concomitant versus 14-d triple seem to be appropriate according to current Guidelines and would clarify which regimen is the most suitable worldwide. Additionally, in this metaanalysis concomitant and sequential therapy showed similar performances, despite it is common opinion that sequential is more prone than concomitant therapy to fail when metronidazole resistance occurs, and China is characterized by high rate of resistance to this antibiotic. None of the included studies evaluated a priori antibiotic resistances, and the lack of this detail hampers the unveiling of this apparent contradiction. In conclusion, the lack of the evaluation of the quality of included trials as well as their high heterogeneity constitute a burdensome limit to draw solid conclusions in this meta-analysis. On the bases of these considerations and the low number of examined trials, we believe that further studies and the knowledge of antibiotic resistances will support with high quality evidence which is the best regimen and its optimal duration.

关键词： Helicobacter pylori Eradication Sequential Concomitant Triple therapy Antibiotic resistances

Noninvasive molecular analysis of Helicobacter pylori : Is it time for tailored first-line therapy?

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World Journal of Gastroenterology 2017年第14期23卷 2453-2458页

作者： Enzo Ierardi Floriana Giorgio Andrea Iannone giuseppe losurdo Mariabeatrice Principi Michele Barone Antonio Pisani Alfredo Di Leo Gastroenterology Section Department of Emergency and Organ Transplantation University of Bari

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 su

关键词： Helicobacter pylori 抗菌素抵抗 Noninvasive 分子的测试定制的治疗凳子

Serologic diagnosis of celiac disease: May it be suitable for adults?

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World Journal of Gastroenterology 2021年第42期27卷 7233-7239页

作者： giuseppe losurdo Milena Di Leo Edoardo Santamato Monica Arena Maria Rendina Carmelo Luigiano Enzo Ierardi Alfredo Di Leo Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Unit of Digestive Endoscopy San Paolo HospitalMilan 20090Italy

The diagnosis of coeliac disease(CD)in adult patients requires the simultaneous assessment of clinical presentation,serology,and typical histological picture of villous ***,several years ago,the European Society of Pediatric Gastroenterology,Hepatology,and Nutrition guidelines approved new criteria for the diagnosis in children:Biopsy could be avoided when antitransglutaminase antibody(TGA)values exceed the cut-off of×10 upper limit of normal(ULN)and anti-endomysium antibodies are positive,independently from ***“no biopsy”approach is a decisive need for pediatric population,allowing to avoid stressful endoscopic procedures in children,if *** approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh’s *** lines of evidence have shown that patients with villous atrophy have markedly elevated TGA ***,we aim to perform a narrative review on the topic in *** that some studies confirmed that the×10 ULN threshold value has a very good diagnostic performance,several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological *** conclusion,the heterogeneity of study reports as well as some conditions,which may hamper the serological diagnosis of CD(such as seronegative CD and non-celiac villous atrophy)and are much more common in adults than in children,could represent a limitation for the“no biopsy”approach to CD diagnosis in patients outside the pediatric age.

关键词： Celiac disease Villous atrophy Serology Biopsy Anti-transglutaminase antibody