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Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

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World Journal of Transplantation 2024年第1期14卷 72-83页

作者： maurizio Salvadori Giuseppina Rosso Department of Renal Transplantation Careggi University HospitalFlorence 50139TuscanyItaly Division of Nephrology San Giovanni di Dio HospitalFlorence 50143ToscanaItaly

Gut microbiota is often modified after kidney transplantation.This principally happens in the first period after transplantation.Antibiotics and,most of all,immunosuppressive drugs are the main responsible.The relationship between immunosuppressive drugs and the gut microbiota is bilateral.From one side immunosuppressive drugs modify the gut microbiota,often generating dysbiosis;from the other side microbiota may interfere with the immunosuppressant pharmacokinetics,producing products more or less active with respect to the original drug.These phenomena have influence over the graft outcomes and clinical consequences as rejections,infections,diarrhea may be caused by the dysbiotic condition.Corticosteroids,calcineurin inhibitors such as tacrolimus and cyclosporine,mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known.In contrast is well known how the gut microbiota may interfere with glucocorticoids,which may be transformed into androgens.Tacrolimus may be transformed by microbiota into a product called M1 that is 15-fold less active with respect to tacrolimus.The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glucuronidase,may be transformed into the inactive product.

关键词： Immunosuppressive therapy Kidney transplantation Gut microbiota Dysbiosis Pathobionts Graft outcomes

Genetic testing in neurology exploiting next generation sequencing:state of art

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Neural Regeneration Research 2020年第2期15卷 265-266页

作者： Chiara Di Resta maurizio ferrari Vita-Salute San Raffaele University MilanItaly Unit of Genomics for Human Disease Diagnosis Division of Genetics and Cell BiologyIRCCS San Raffaele Scientific InstituteMilanItaly Clinical Molecular Biology Laboratory IRCCS San Raffaele HospitalMilanItaly

Next generations sequencing (NGS) is definitely one of the most revolutionary technology of the last years in genetic and medical field (Kricka and Di Resta, 2013). It brought important changes in genetic testing of inherited human disorders, in particular in neurological Mendelian forms, such as inherited neuropathies, ataxias or monogenic form of epilepsy, where “diagnostic odyssey” is quite common.

关键词： Genetic testing NGS diagnostic odyssey

Current scenario of the genetic testing for rare neurological disorders exploiting next generation sequencing

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Neural Regeneration Research 2021年第3期16卷 475-481页

作者： Chiara Di Resta Giovanni Battista Pipitone Paola Carrera maurizio ferrari Vita-Salute San Raffaele University MilanItaly Unit of Genomics for Human Disease Diagnosis Division of Genetics and Cell BiologyIRCCS San Raffaele Scientific InstituteMilanItaly Clinical Molecular Biology Laboratory IRCCS San Raffaele HospitalMilanItaly

Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous diseases,such as neurological disorders.It is a fast-moving field,where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations.Despite the as yet undiscussed advantages,however,there are still some challenges in data analysis and the interpretation of variants.In this review,we address the current state of next generation sequencing diagnostic testing for inherited human disorders,particularly giving an overview of the available high-throughput sequencing approaches;including targeted,whole-exome and whole-genome sequencing;and discussing the main critical aspects of the bioinformatic process,from raw data analysis to molecular diagnosis.

关键词： clinical practice genetic testing neurogenesis next generation sequencing sequencing approaches variant interpretation

Epoché as the Breakthrough of the Natural Attitude

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Philosophy Study 2024年第3期14卷 138-144页

作者： maurizio Trudu Universitàdegli Studi di Ferrara FerraraItaly Bergische Universität Wuppertal WuppertalGermany

The following contribution aims to interpret the methodical device of Husserl’s epochéin light of the concept of breakthrough.Since the epochéis a theoretical device directed towards the suspension of the natural attitude,I will first attempt to define the concept of natural attitude.Subsequently,I will seek to understand the rich meaning of the concept of epoché.Finally,I will explore how this element is related to the concept of breakthrough.In other words,I will endeavour to clarify how the epochédetermines a breakthrough of the natural attitude,which is not to be understood as“annihilation”or“destruction”but as a traversal.

关键词： Edmund Husserl epoché natural attitude phenomenology

Frequency of and reasons behind non-listing in adult patients referred for liver transplantation: Results from a retrospective study

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World Journal of Transplantation 2024年第2期14卷 99-106页

作者： Marco Biolato Luca Miele Giuseppe Marrone Claudia Tarli Antonio Liguori Rosaria Calia Giovanni Addolorato Salvatore Agnes Antonio Gasbarrini maurizio Pompili Antonio Grieco Department of Medical and Surgical Sciences CEMADFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy Department of Translational Medicine and Surgery Catholic University of Sacred HeartRome 00168Italy

BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates.AIM To assess the ineligibility rate for liver transplantation and its motivations.METHODS A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation eligibility.The predictors for listing were evaluated using multivariable logistic regression.RESULTS In our center,314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year period.The most frequent reasons for transplant evaluation were decompensated cirrhosis(51.6%)and hepatocellular carcinoma(35.7%).The non-listing rate was 53.8%and the transplant rate was 34.4%for the whole cohort.Two hundred and five motivations for ineligibility were collected.The most common contraindications were psychological(9.3%),cardiovascular(6.8%),and surgical(5.9%).Inappropriate or premature referral accounted for 76(37.1%)cases.On multivariable analysis,a referral from another hospital(OR:2.113;95%CI:1.259–3.548)served as an independent predictor of non-listing.CONCLUSION A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of three.The referral from another hospital was taken as a strong predictor of non-listing.

关键词： Controindication Eligibility Evaluation Referral Personalized medicine

Conservative management of an early abdominal complication during a Tullio percutaneous endoscopic excision of renal pelvis urothelial carcinoma:A case report

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World Journal of Clinical Urology 2024年第1期13卷 1-6页

作者： Massimiliano Bernabei NicolòFabbri Danila Romeo Elisa Paiolo Martina Bandi maurizio Simone Department of Urology Azienda USL di FerraraFerrara 44100Italy Department of Surgery University of FerraraAzienda USL of FerraraAzienda USL of FerraraFerrara 44100FerraraItaly Local Health Agency of Ferrara Ferrara 44100Italy

BACKGROUND Upper tract urothelial carcinoma(UTUC)representing only a small fraction of all urothelial tumors.It predominantly affects the renal pelvis in men,often coexisting with bladder carcinoma.UTUC displays a more aggressive genetic profile compared to bladder neoplasms,with the majority of patients presenting with advanced disease.Histologically,about a quarter of UTUC cases exhibit high-grade subtypes,associated with a worse prognosis.Tobacco use and past exposure to aromatic amines are significant risk factors for UTUC.Imaging modalities such as Uro-computed tomography and magnetic resonance imaging play crucial roles in diagnosis.Ureterorenoscopy is vital for direct visualization and biopsy sampling,but its limited sampling capacity presents challenges in determining tumor depth and staging.Traditionally,nephroureterectomy with bladder cuff excision has been the gold-standard treatment for UTUC.Endoscopic conservative treatment has recently emerged as a viable option for selected patients,offering comparable oncological outcomes to radical surgery.Percutaneous access is also feasible for larger intrarenal tumors.CASE SUMMARY We present a case of an 84-year-old woman who underwent percutaneous endoscopic excision of a renal pelvis neoplasm using the Tullio laser.Despite successful tumor removal,the patient experienced a postoperative complication with abdominal fluid leakage.Conservative management effectively resolved the complication.Given the patient's age and refusal for radical surgery,the conservative approach proved to be a valid therapeutic choice.CONCLUSION Overall,UTUC remains a diagnostic and therapeutic challenge due to its rarity.However,advances in endoscopic and percutaneous techniques provide valuable alternatives for selected patients,warranting further exploration in this evolving field.

关键词： Upper tract urothelial carcinoma Endoscopic treatment Damage management Case report

Update on the gut microbiome in health and diseases

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World Journal of Methodology 2024年第1期14卷 18-32页

The Human Microbiome Project,Earth Microbiome Project,and next-generation sequencing have advanced novel genome association,host genetic linkages,and pathogen identification.The microbiome is the sum of the microbes,their genetic information,and their ecological niche.This study will describe how millions of bacteria in the gut affect the human body in health and disease.The gut microbiome changes in relation with age,with an increase in Bacteroidetes and Firmicutes.Host and environmental factors affecting the gut microbiome are diet,drugs,age,smoking,exercise,and host genetics.In addition,changes in the gut microbiome may affect the local gut immune system and systemic immune system.In this study,we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases.Due to the high number of publications on the argument,from a methodologically point of view,we decided to select the best papers published in referred journals in the last 3 years.Then we selected the previously published papers.The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.

关键词： Gut microbiome Dysbiosis Pathobionts Gut-brain axis Heart-brain axis Metabolic diseases Omics techniques

Optic nerve crush as a model of retinal ganglion cell degeneration

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Annals of Eye Science 2022年第2期7卷 27-32页

作者： maurizio Cammalleri Department of Biology University of PisaPisaItaly

Background:Axonal degeneration caused by damage to the optic nerve can result in a gradual death of retinal ganglion cells(RGC),leading to irreversible vision loss.An example of such diseases in humans includes optic nerve degeneration in glaucoma.Glaucoma is characterized by the progressive degeneration of the optic nerve and the loss of RGCs that can lead to loss of vision.The different animal models developed to mimic glaucomatous neurodegeneration,all result in RGC loss consequent optic nerve damage.Methods:The present article summarizes experimental procedures and analytical methodologies related to one experimental model of glaucoma induced by optic nerve crush(ONC).Point-by-point protocol is reported with a particular focus on the critical point for the realization of the model.Moreover,information on the electroretinogram procedure and the immunohistochemical detection of RGCs are described to evaluate the morpho-functional consequences of ONC.Discussion:Although the model of ONC is improperly assimilated to glaucoma,then the ONC model simulates most of the signaling responses consequent to RGC apoptosis as observed in models of experimental glaucoma.In this respect,the ONC model may be essential to elucidate the cellular and molecular mechanisms of glaucomatous diseases and may help to develop novel neuroprotective therapies.

关键词： Axonal injury retrograde degeneration cell death

Management of gastro-esophageal reflux disease:Practice-oriented answers to clinical questions

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World Journal of Gastroenterology 2023年第5期29卷 773-779页

作者： Leonardo Frazzoni Lorenzo Fuccio Rocco maurizio Zagari Department of Digestive Diseases IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S OrsolaBologna 40138Italy Department of Medical and Surgical Sciences University of BolognaBologna 40138Italy

Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource utilization.In fact,the management of patients with GERD is complex and poses several questions to the clinician who faces them in clinical practice.For instance,many aspects should be considered,including the appropriateness of indication to endoscopy,the quality of the endoscopic examination,the use and interpretation of ambulatory reflux testing,and the choice and management of anti-reflux treatments,i.e.,protonpump inhibitors and surgery.Aim of the present review was to provide a comprehensive update on the clinical management of patients with GERD,through a literature review on the diagnosis and management of patients with GER symptoms.In details,we provide practice-oriented concise answers to clinical questions,with the aim of optimising patient management and healthcare resource use.

关键词： Gastro-esophageal reflux disease Diagnosis Management Proton-pump inhibitor