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Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease

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World Journal of Gastroenterology 2013年第39期19卷 6529-6535页

作者： michele Cicala Sara Emerenziani michele pier luca guarino Mentore Ribolsi Unit of Digestive Disease Campus Bio Medico University of Rome00128 RomeItaly

Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic *** 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 *** 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 *** 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 *** has been primarily based on doubling the PPI dose or switching to another *** with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.

关键词： Gastro-esophageal reflux disease Proton pump inhibitor Ambulatory pH-impedance monitoring Esophageal hypersensitivity Gastro-esophageal reflux disease treatment

Gastroesophageal reflux disease: Update on inflammation and symptom perception

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World Journal of Gastroenterology 2013年第39期19卷 6523-6528页

作者： Annamaria Altomare michele pier luca guarino Silvia Cocca Sara Emerenziani michele Cicala Unit of Digestive Disease Campus Bio Medico University of Rome00128 RomeItaly

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 *** symptoms and complications may result from a multifactorial mechanism,in which acid and acid-pepsin are the important noxious factors *** 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 *** on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity,as suggested in animal models of chronic acid ***,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 *** 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 ***,the large majority of GERD patients(up to 70%)do not develop esophageal erosions,a variant of the condition called non-erosive reflux *** 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.

关键词： Gastroesophageal reflux disease Mucosal inflammation Heartburn Esophagitis Hypersensitivity

Gastro-esophageal reflux disease and obesity, where is the link?

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World Journal of Gastroenterology 2013年第39期19卷 6536-6539页

作者： Sara Emerenziani Maria Paola Rescio michele pier luca guarino michele Cicala Unit of Digestive Disease Campus Bio Medico University of Rome00128 RomeItaly

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 *** 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 *** 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 *** 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.

关键词： Body mass index Visceral obesity Gastroesophageal reflux Gastro-esophageal reflux disease complication

Ursodeoxycholic acid therapy in gallbladder disease,a story not yet completed

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World Journal of Gastroenterology 2013年第31期19卷 5029-5034页

作者： michele pier luca guarino Silvia Cocca Annamaria Altomare Sara Emerenziani michele Cicala Department of Digestive Disease Campus Bio Medico University 00128 RomeItaly

Gallstone disease represents an important issue in the healthcare *** principal non-invasive nonsurgical medical treatment for cholesterol gallstones is still represented by oral litholysis with bile *** first successful and documented dissolution of cholesterol gallstones was achieved in *** 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 *** 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.

关键词： Gallbladder Cholesterol gallstones Ursodeoxycholic acid

Eosinophilic esophagitis: New insights in pathogenesis and therapy

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第1期7卷 66-77页

作者： michele pier luca guarino michele Cicala Jose Behar Unit of Digestive Disease Campus Bio Medico University of Rome Brown University Medical School

Eosinophilic esophagitis(Eo E) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multiorgan involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with Eo E depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect.

关键词： Eosinophilic esophagitis Gastro-esophageal reflux disease Esophagus Esophagitis Eosinophilia Cytokines

Starring role of toll-like receptor-4 activation in the gutliver axis

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World Journal of Gastrointestinal Pathophysiology 2015年第4期6卷 99-109页

作者： Simone Carotti michele pier luca guarino Umberto Vespasiani-Gentilucci Sergio Morini Laboratory of Microscopic and Ultrastructural Anatomy School of MedicineUniversity Campus Bio-Medico of Rome Gastroenterology Unit School of Medicine University Campus Bio-Medico of Rome Clinical Medicine and Hepatology Unit School of Medicine University Campus Bio-Medico of Rome

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.

关键词： Gut microbiota Dysbiosis Toll-like receptor 4 Gut

Impact of chronic kidney disease on mortality in older adults treated with pacemaker implantation

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Journal of Geriatric Cardiology 2017年第10期14卷 597-603页

作者： Fabio Fabbian Alfredo De Giorgi Matteo guarino michele Malagu Matteo Bertini Department of Medical Sciences Clinical Medical Unit University Hospital St. Anna University of Ferrara Ferrara Italy Department of Medical Sciences Cardiology Unit University Hospital St. Anna University of Ferrara Ferrara Italy

Objective To investigate whether chronic kidney disease could negatively impact survival in older adults needing pacemaker implantation after admission for bradyarrhythmias. Methods This retrospective observational study considered 538 older adults consecutively admitted, who had been followed-up for 31 ± 20 months. Subjects with poor short-term prognosis were excluded. Charlson comorbidity index （CCI） and estimated glomerular filtration rate （eGFR） was calculated, along with the independent relationship between all-cause mortality and clinical data. Hazard Ratio （HR） was calculated by Cox regression analysis. Results Mean age of the population was 85 ± 3.7 years, and causes for implantation were atrioventricular block in 51.9% and other bradyarrhythmias in 48.1% of cases. Mean eGFR was 58.3 ± 24 mL/min per 1.73 m2, and mean CCI was 3.65 ± 2.28. Death for all-causes was recorded in 213 subjects. Deceased patients were older, had lower eGFR, higher comorbidity, higher prevalence of myocardial infarction, congestive heart failure, cerebrovascular disease, dementia and chronic pulmonary disease. Age （HR： 1.081, 95% CI： 1.044-1.119; P 〈 001）, CCI （HR： 1.651, 95% CI： 1.286-2.121, P 〈 001） and eGFR 〈 45 mL/min per 1.73 m2 （HR： 1.360, 95% CI： 1.024-1.806; P = 0.033） were predictors of death. Conclusions Renal dysftmction, as well as comorbidity, impacts negatively survival of older adults treated with pacemaker implantation because of bradyarrhythmias.

关键词： Bradyarrhythmias Charlson comorbidity index Chronic kidney disease Comorbidity Glomerular filtration rate Mortality Pacemaker

Colorectal cancer: Parametric evaluation of morphological,functional and molecular tomographic imaging

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World Journal of Gastroenterology 2019年第35期25卷 5233-5256页

作者： pier Paolo Mainenti Arnaldo Stanzione Salvatore guarino Valeria Romeo Lorenzo Ugga Federica Romano Giovanni Storto Simone Maurea Arturo Brunetti Institute of Biostructures and Bioimaging of the National Council of Research (CNR) Naples 80145 Italy University of Naples "Federico II" Department of Advanced Biomedical Sciences Naples 80131 Italy IRCCS-CROB Referral Cancer Center of Basilicata Rionero in Vulture 85028 Italy

Colorectal cancer (CRC) represents one of the leading causes of tumor-related deaths worldwide. Among the various tools at physicians’ disposal for the diagnostic management of the disease, tomographic imaging (e.g., CT, MRI, and hybrid PET imaging) is considered essential. The qualitative and subjective evaluation of tomographic images is the main approach used to obtain valuable clinical information, although this strategy suffers from both intrinsic and operator-dependent limitations. More recently, advanced imaging techniques have been developed with the aim of overcoming these issues. Such techniques, such as diffusion-weighted MRI and perfusion imaging, were designed for the “in vivo” evaluation of specific biological tissue features in order to describe them in terms of quantitative parameters, which could answer questions difficult to address with conventional imaging alone (e.g., questions related to tissue characterization and prognosis). Furthermore, it has been observed that a large amount of numerical and statistical information is buried inside tomographic images, resulting in their invisibility during conventional assessment. This information can be extracted and represented in terms of quantitative parameters through different processes (e.g., texture analysis). Numerous researchers have focused their work on the significance of these quantitative imaging parameters for the management of CRC patients. In this review, we aimed to focus on evidence reported in the academic literature regarding the application of parametric imaging to the diagnosis, staging and prognosis of CRC while discussing future perspectives and present limitations. While the transition from purely anatomical to quantitative tomographic imaging appears achievable for CRC diagnostics, some essential milestones, such as scanning and analysis standardization and the definition of robust cut-off values, must be achieved before quantitative tomographic imaging can be incorporated into

关键词： Colorectal cancer Computed tomography Magnetic resonance imaging Positron emission tomography Parametric imaging Perfusion imaging Diffusion imaging Texture analysis

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

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World Journal of Gastroenterology 2024年第15期30卷 2081-2086页

作者： michele Nardolillo Fabiola Rescigno Mario Bartiromo Dario Piatto Stefano guarino pierluigi Marzuillo Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Naples 80138Italy

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant ***,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since *** recently,this term has been further replaced with metabolic associated steatotic liver *** is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic ***,comparable pediatric data remain *** the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

关键词： Metabolic(dysfunction)associated fatty liver disease Renal Function Children Obesity