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| 1 | Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease显示文摘Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery. | Michele Cicala Sara Emerenziani Michele Pier Luca Guarino Mentore Ribolsi | 2013 | World Journal of Gastroenterology2013，19，39： | 38 |
| 2 | 欧洲儿童急性胃肠炎处理循证指南(2014年版)显示文摘1991年世界卫生组织(WHO)制订了第一版儿童急性腹泻病指南,2005年WHO和联合国儿童基金会(UNICEF)制订了第二版,我国专家在参照WHO指南的基础上,结合我国国情分别于1993年、2009年制订了中国儿童急性腹泻病的专家共识;WH0指南和我国共识对中国儿童急性腹泻病的规范诊治发挥了重要的作用,收到了良好的效果。时至今日,欧洲儿科胃肠病学、肝病学和营养协会及欧洲儿科感染病协会对2008年儿童急性胃肠炎循证指南进行更新,即“2014年版”。指南中腹泻病原、低渗口服补液盐溶液使用、营养管理和常规对症治疗与我国现行共识基本一致。另首次对儿童脱水评估和疾病严重程度评分进行量化并提出通过鼻胃管补液,这是我们可以借鉴的。重度脱水休克的治疗强调了可重复3次20ml/kg0.9%氯化钠溶液,与我国危重专业观点相一致。静脉补充液体成分与我国现行共识存在差异,与指南执笔者之一意大利学者AndreaLoVecehio进行交流,其认同我国现用液体组成。细菌感染所致腹泻使用抗生素的指征与我国现行共识相同,但在抗生素选择上存在差异,建议根据我国药典和药敏结果选择合适抗生素。由于我国社会经济、文化和医学发展等与欧洲存在差异,因此指南中的观点、方法等应结合中国特点进行应用。 | Alfredo Guarino Shai Ashkenazi Dominique Gendrel Andrea Lo Vecchio Raanan Shamir Hania Szajewska 方铁夫 耿岚岚 龚四堂 | 2015 | 中华儿科杂志2015，53，7： | 30 |
| 3 | Gastroesophageal reflux disease: Update on inflammation and symptom perception显示文摘Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated.GERD symptoms and complications may result from a multifactorial mechanism,in which acid and acid-pepsin are the important noxious factors involved.Prolonged contact of the esophageal mucosa with the refluxed content,probably caused by a defective anti-reflux barrier and luminal clearance mechanisms,would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium.Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity,as suggested in animal models of chronic acid exposure.Meanwhile,specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD,explaining,in part,the genesis of esophagitis in a subset of patients.Despite these findings,which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD,the relationship between the hypersensitivity and esophageal inflammation is not clear.Moreover,the large majority of GERD patients(up to 70%)do not develop esophageal erosions,a variant of the condition called non-erosive reflux disease.This summary aims to explore the inflammatory pathway involved in GERD pathogenesis,to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches. | Annamaria Altomare Michele Pier Luca Guarino Silvia Cocca Sara Emerenziani Michele Cicala | 2013 | World Journal of Gastroenterology2013，19，39： | 16 |
| 4 | Ursodeoxycholic acid therapy in gallbladder disease,a story not yet completed显示文摘Gallstone disease represents an important issue in the healthcare system.The principal non-invasive nonsurgical medical treatment for cholesterol gallstones is still represented by oral litholysis with bile acids.The first successful and documented dissolution of cholesterol gallstones was achieved in 1972.Since then a large number of investigators all over the world,have been dedicated in biochemical and clinical studies on ursodeoxycholic acid(UDCA),demonstrating its extreme versatility.This editorial is aimed to provide a brief review of recent developments in UDCA use,current indications for its use and,the more recent advances in understanding its effects in terms of an antiinflammatory drug. | Michele Pier Luca Guarino Silvia Cocca Annamaria Altomare Sara Emerenziani Michele Cicala | 2013 | World Journal of Gastroenterology2013，19，31： | 16 |
| 5 | Probiotics for gastrointestinal disorders: Proposed recommendations for children of the Asia-Pacific region显示文摘Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects,health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745(Sb) and Lactobacillus rhamnosus GG(LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of(with the indicated strains): antibiotic-associated diarrhea(LGG or Sb); Clostridium difficile-induced diarrhea(Sb); nosocomial diarrhea(LGG); infantile colic(L reuteri) and as adjunct treatment of Helicobacter pylori(Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological,socioeconomical and health system conditions,similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials. | Donald Cameron Quak Seng Hock Musal Kadim Neelam Mohan Eell Ryoo Bhupinder Sandhu Yuichiro Yamashiro Chen Jie Hans Hoekstra Alfredo Guarino | 2017 | World Journal of Gastroenterology2017，23，45： | 14 |
| 6 | Gastrointestinal neuromuscular apparatus: An underestimated target of gut microbiota显示文摘Over the last few years, the importance of the resident intestinal microbiota in the pathogenesis of several gastrointestinal diseases has been largely investigated. Growing evidence suggest that microbiota can influence gastrointestinal motility. The current working hypothesis is that dysbiosis-driven mucosal alterations induce the production of several inflammatory/immune mediators which affect gut neuro-muscular functions. Besides these indirect mucosal-mediated effects, the present review highlights that recent evidence suggests that microbiota can directly affect enteric nerves and smooth muscle cells functions through its metabolic products or bacterial molecular components translocated from the intestinal lumen. Tolllike receptors, the bacterial recognition receptors, are expressed both on enteric nerves and smooth muscle and are emerging as potential mediators between microbiota and the enteric neuromuscular apparatus. Furthermore, the ongoing studies on probiotics support the hypothesis that the neuromuscular apparatus may represent a target of intervention, thus opening new physiopathological and therapeutic scenarios. | Michele Pier Luca Guarino Michele Cicala Lorenza Putignani Carola Severi | 2016 | World Journal of Gastroenterology2016，22，45： | 8 |
| 7 | Starring role of toll-like receptor-4 activation in the gutliver axis显示文摘Since the introduction of the term 'gut-liver axis', many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4(TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types. | Simone Carotti Michele Pier Luca Guarino Umberto Vespasiani-Gentilucci Sergio Morini | 2015 | World Journal of Gastrointestinal Pathophysiology2015，6，4： | 8 |
| 8 | Serrated polyposis syndrome:Molecular,pathological and clinical aspects显示文摘Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area.Until recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found thatthis pathway accounts for only approximately 70%-80% of colorectal cancer(CRC)cases.The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability.The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene.Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon.Clinical characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet.Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described.Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer.In this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome. | Carla Guarinos Cristina Sánchez-Fortún María Rodríguez-Soler Cristina Alenda Artemio Payá Rodrigo Jover | 2012 | World Journal of Gastroenterology2012，18，20： | 8 |
| 9 | Gastro-esophageal reflux disease and obesity, where is the link?显示文摘The confluence between the increased prevalence of gastro-esophageal reflux disease(GERD)and of obesity has generated great interest in the association between these two conditions.Several studies have addressed the potential relationship between GERD and obesity,but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined.A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter,thus exposing the esophageal mucosal to gastric content.Apart from the mechanical pressure,visceral fat is metabolically active and it has been strongly associated with serum levels of adipocytokines including interleukin-6 and tumor necrosis factorα,which may play a role in GERD or consequent carcinogenesis.This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity,and to better understand the possible role of weight loss as a therapeutic approach for GERD. | Sara Emerenziani Maria Paola Rescio Michele Pier Luca Guarino Michele Cicala | 2013 | World Journal of Gastroenterology2013，19，39： | 7 |
| 10 | Gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy in the years 2000显示文摘AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: 'gastrointestinal infection AND antineoplastic chemotherapy AND children', 'gastrointestinal infection AND oncology AND children', 'liver infection AND antineoplastic chemotherapy AND children', 'liver abscess AND chemotherapy AND child', 'neutropenic enterocolitis AND chemotherapy AND children', 'thyphlitis AND chemotherapy AND children', 'infectious diarrhea AND children AND oncology', 'abdominal pain AND infection AND children AND oncology', 'perianal sepsis AND children AND oncology', 'colonic pseudo-obstruction A N D o n c o l o g y A N D c h i l d A N D c h e m o t h e r a p y ', 'microflora AND children AND malignancy', 'microbiota AND children AND malignancy', 'fungal flora AND children AND malignancy'. We also analysed evidence from several articles and book references.RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infectionin those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available. CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented(also by further studies on new biomarkers) for a prompt and individualized therapy. | Elio Castagnola Eliana Ruberto Alfredo Guarino | 2016 | World Journal of Gastroenterology2016，22，25： | 6 |
| 11 | Hepatitis B and C virus reactivation in immunosuppressed patients with inflammatory bowel disease显示文摘In recent years,a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs.The cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations,from viremia without clinically relevant manifestations to fulminant life-threatening hepatitis.The development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical settings.On this topic,there have been a number of published guidelines and reviews that have collected the available evidence,providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at risk.However,it should be noted that,to date,very few clinical studies have been published,and most of the recommendations have been borrowed from otherclinical settings.The published studies are mostly retrospective and are based on very heterogeneous populations,using different therapeutic and prophylactic regimens and obtaining conflicting results.Thus,it seems clear that it is desirable to concentrate our efforts on prospective studies,not conducting further reviews of the literature in the continued absence of new evidence. | Stefano Sansone Maria Guarino Fabiana Castiglione Antonio Rispo Francesco Auriemma Ilaria Loperto Matilde Rea Nicola Caporaso Filomena Morisco | 2014 | World Journal of Gastroenterology2014，20，13： | 6 |
| 12 | Systematic review and meta‐analysis of randomized clinical trials comparing single‐incision versus conventional laparoscopic cholecystectomy显示文摘 | S. Trastulli R. Cirocchi J. Desiderio S. Guarino A. Santoro A. Parisi G. Noya C. Boselli | 2012 | Br J Surg2012，，2： | 5 |
| 13 | Sustained virological response: A milestone in the treatment of chronic hepatitis C显示文摘AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples 'Federico Ⅱ'. At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years. | Filomena Morisco Rocco Granata Tommaso Stroffolini Maria Guarino Laura Donnarumma Laura Gaeta Ilaria Loperto Ivan Gentile Francesco Auriemma Nicola Caporaso | 2013 | World Journal of Gastroenterology2013，19，18： | 4 |
| 14 | Growth hormone regulates intestinal ion transport through a modulation of the constitutive nitric oxide synthase-nitric oxide-cAMP pathway显示文摘瞄准:生长激素(GH ) 直接与刺激离子吸收并且减少营地的收缩筋导致的离子分泌物的 enterocyte 交往。后来氮的氧化物(没有) 为 GH 血液动力学的效果作为第二个送信人涉及 transepithelial 离子运输和行为的规定,我们测试了可以不在肠的离子运输上涉及 GH 的产生效果的假设。方法:反映 trans 上皮的离子运输的电的参数在房间单层在 Ussing 房间装了并且独自或在联合暴露了到 GH 和霍乱毒素(CT ) 的 Caco-2 被测量,当面或 NO 的缺席 synthase (NOS ) 禁止者, Nomega-nitro-L-arginine 甲基酉旨(L 名字) 。类似的实验被进行决定营地和亚硝酸根 / 硝酸盐集中。NOS 表示是由西方的污点分析的 assayed。结果:L 名字原因在肠的离子运输上由 GH 总计吸收性、反能分泌的效果的废除。另外, L 名字能在基础条件下面并且响应 CT 在细胞内部的营地集中上禁止 GH 效果。GH 导致了 Ca (2+) 亚硝酸根 / 硝酸盐生产的依赖增加,显示参与组成而非可诱导的 NOS 对碘氧基苯甲醚,它被西方的污点分析直接证实。结论:这些结果建议在基础条件下面或面对刺激营地的离子分泌物,肠的离子运输上的 GH 效果被 cNOS 的活动在细胞内部的水平调停。 | Roberto Berni Canani Pia Cirillo Giuseppe Mallardo Vittoria Buccigrossi Annalisa Passariello Serena Ruotolo Giulio De Marco Francesco Porcaro Alfredo Guarino | 2006 | World Journal of Gastroenterology2006，12，29： | 3 |
| 15 | Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows显示文摘With the introduction of direct-acting antiviral agents(DAA), the rate of sustained virological response(SVR) in the treatment of hepatitis C virus(HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma(HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4%(maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4%(maximum 'not well-defined' followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. | Maria Guarino Anna Sessa Valentina Cossiga Federica Morando Nicola Caporaso Filomena Morisco | 2018 | World Journal of Gastroenterology2018，24，24： | 2 |
| 16 | Direct contribution of epithelium to organ fibrosis: epithelial-mesenchymal transition显示文摘 | Marcello Guarino Antonella Tosoni Manuela Nebuloni | 2009 | Human Pathology2009，，10： | 2 |
| 17 | HCl-induced and ATP-dependent upregulation of TRPV1 receptor expression and cytokine production by human esophageal epithelial cells显示文摘 | Jie Ma Annamaria Altomare Michele Guarino Michele Cicala Florian Rieder Claudio Fiocchi Dan Li Weibiao Cao Jose Behar Piero Biancani Karen M. Harnett | 2012 | AJP: Gastrointestinal and Liver Physiology2012，，5： | 2 |
| 18 | Rituximab-induced IgG hypogammaglobulinemia in children with nephrotic syndrome and normal pre-treatment IgG values显示文摘BACKGROUND In paediatric patients with complicated nephrotic syndrome(NS), rituximab(RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G(IgG) levels.AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels.METHODS We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation(SD)].RESULTS We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients(55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two 'starting doses' experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth dose.CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections. | Pierluigi Marzuillo Stefano Guarino Tiziana Esposito Anna Di Sessa Sara Immacolata Orsini Daniela Capalbo Emanuele Miraglia del Giudice Angela La Manna | 2019 | World Journal of Clinical Cases2019，7，9： | 2 |
| 19 | Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subar- achnoid hemorrhage in the rat显示文摘 | Bederson JB Germano IM Guarino L | 1995 | Stroke1995，26，6： | 1 |
| 20 | Lonidamine transiently affects spermatogenesis in pubertal CD1 mice显示文摘 | Traina ME Guarino M Urbani E | 2005 | Contraception2005，72，4： | 1 |
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