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Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis

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World Journal of Gastroenterology 2019年第12期25卷 1465-1477页

作者： Valentina Petito Cristina Graziani Loris R Lopetuso Marco Fossati Alessandra Battaglia Vincenzo Arena Domenico Scannone Gianluca Quaranta Andrea Quagliariello Federica Del Chierico Lorenza Putignani Luca Masucci Maurizio Sanguinetti Alessandro Sgambato Antonio Gasbarrini Franco Scaldaferri Istituto di Patologia Speciale medica Università Cattolica del Sacro Cuore UOC di Medicina Interna e Gastroenterologia Area di Gastroenterologia e Oncologia Medica Dipartimento di Scienze Gastroenterologiche Endocrino-Metaboliche e Nefro-Urologiche Fondazione Policlinico Universitario "A. Gemelli" IRCCS Dipartimento delle Scienze della Salute della Donna e del Bambino Fondazione Policlinico Universitario "A. Gemelli" IRCCS Istituto di clinica Ostetrica e Ginecologica Università Cattolica del Sacro Cuore U.O.S.A. Gineco-Patologia e Patologia Mammaria Fondazione Policlinico Universitario "A. Gemelli" IRCCS Istituto di Anatomia Patologica Università Cattolica del Sacro Cuore Dipartimento di Anatomia Patologica e Istologia Fondazione Policlinico Universitario "A. Gemelli" IRCCS Dipartimento di Microbiologia Fondazione Policlinico Universitario "A. Gemelli" IRCCS Istituto di Microbiologia Università Cattolica del Sacro Cuore Unità di Microbioma Umano Ospedale Pediatrico Bambino Gesù IRCCS Unità di Parassitologia Ospedale Pediatrico Bambino Gesù IRCCS Istituto di Patologia Generale Università Cattolica del Sacro Cuore

BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing.AIM To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium(DSS) colitis.MeTHODS eighty C57 BL/6 mice were divided into four groups: "No DSS", "No DSS + antiTNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and"DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score(Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, enterococcaceae and Fecalibacterium prausnitzii(F. prausnitzii) were evaluated by quantitative PCR.Type 1 helper T lymphocytes(Th1), type 17 helper T lymphocytes(Th17) and CD4+ regulatory T lymphocytes(Treg) distributions in the mesenteric lymph node(MLN) were studied by flow cytometry.ReSULTS Bacteria associated with a healthy state(i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFαtreatment. Conversely, microorganisms belonging to enterococcaceae genera,which are linked to inflammatory processes, showed an opposite trend.Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase(day 5 of the colitis) in Treg cells and a consequent decrease(day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNF

关键词： Gut microbiota Dextran sodium sulphate colitis Immune system T cells Mesenchymal lymphnode Tumor necrosis factor α

Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani elena Gianni Luca Boni Giacomo Laffi Francesco Di Costanzo Fabio Marra Dipartimento di Medicina Sperimentale e clinica Università degli Studi di Firenze Oncologia medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established cirrhosis.MeTHODS:From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled.According to the Barcelona Clinic Liver Cancer(BCLC)classification,patients were in the advanced stage(BCLC-C)or in the intermediate stage(BCLC-B)but unfit or unresponsive to other therapeutic strategies.Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response evaluation Criteria in Solid Tumors.Sorafenib was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(Aes).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.ReSULTS:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of B7.Aes caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,Pe BCLC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years.After 16 wk of treatment,18 patients(41%)had stable disease or partial response.Patients with viral infection or BCLC-C were at higher risk of disease progression.eCOG,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.CONCLUSION:In patients with cirrhosis and HCC treated with sorafenib,Aes are a common cause of early treatment withdrawal.Vascular invasion and extrahepatic spread condition early response to treatment and survival.Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adver

palliative care and end-stage colorectal cancer management:The surgeon meets the oncologist

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World Journal of Gastroenterology 2014年第24期20卷 7602-7621页

作者： Renato Costi Francesco Leonardi Daniele Zanoni Vincenzo Violi Luigi Roncoroni Istituto di clinica Chirurgica Generale e Terapia Chirurgica Dipartimento di Scienze ChirurgicheUniversità di ParmaAzienda Ospedaliero-Universitaria di Parma43126 ParmaItaly Dipartimento Polispecialistico 1 Unità Operativa di Oncologia MedicaAzienda Ospedaliero-Universitaria di Parma43126 ParmaItaly Dipartimento di Chirurgia Generale e Specialistica Ospedale di VaioAzienda Unità Sanitaria Locale di Parma43036 Fidenza (Parma)Italy

Colorectal cancer(CRC)is a common neoplasia in the Western countries,with considerable morbidity and mortality.every fifth patient with CRC presents with metastatic disease,which is not curable with radical intent in roughly 80%of cases.Traditionally approached surgically,by resection of the primitive tumor or stoma,the management to incurable stageⅣCRC patients has significantly changed over the last three decades and is nowadays multidisciplinary,with a pivotal role played by chemotherapy(CHT).This latter have allowed for a dramatic increase in survival,whereas the role of colonic and liver surgery is nowadays matter of debate.Although any generalization is difficult,two main situations are considered,asymptomatic(or minimally symptomatic)and severely symptomatic patients needing aggressive management,including emergency cases.In asymptomatic patients,new CHT regimens allow today long survival in selected patients,also exceeding two years.The role of colonic resection in this group has been challenged in recent years,as it is not clear whether the resection of primary CRC may imply a further increase in survival,thus justifying surgeryrelated morbidity/mortality in such a class of shortliving patients.Secondary surgery of liver metastasis is gaining acceptance since,under new generation CHT regimens,an increasing amount of patients with distant metastasis initially considered non resectable become resectable,with a significant increase in long term survival.The management of CRC emergency patients still represents a major issue in Western countries,and is associated to high morbidity/mortality.Obstruction is traditionally approached surgically by colonic resection,stoma or internal by-pass,although nowadays CRC stenting is a feasible option.Nevertheless,CRC stent has peculiar contraindications and complications,and its long-term cost-effectiveness is questionable,especially in the light of recently increased survival.Perforation is associated with the highest mortality and remains mostly matter for surgeons,by

关键词： Colorectal cancer Palliative care Multimodal treat

Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

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World Journal of Gastroenterology 2016年第28期22卷 6345-6361页

作者： Vincenzo Sforza erika Martinelli Fortunato Ciardiello Valentina Gambardella Stefania Napolitano Giulia Martini Carminia della Corte Claudia Cardone Marianna L Ferrara Alfonso Reginelli Giuseppina Liguori Giulio Belli Teresa Troiani Oncologia medica Dipartimento di Medicina Clinica e Sperimentale "F. Magrassi e A. Lanzara" Seconda Università degli Studi di Napoli Department of medical Oncology Biomedical Research Institute INCLIVA University of Valencia Department of Internal and experimental Medicine Magrassi-Lanzara Institute of Radiology Seconda Università di Napoli Department of Pathology Istituto Nazionale Tumori "Fond. Pascale" - IRCCS Department of General and Hepato-Pancreato-Biliary Surgery S. M. Loreto Nuovo Hospital

The prognosis of patients with metastatic colorectal cancer(m CRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies(mo Abs) cetuximab and panitumumab, directed against the epidermal growth factor receptor(eGFR), undoubtedly represent a major step forward in the treatment of m CRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase Ⅲ clinical trials among different lines of treatment. However, the anti-eGFR mo Abs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary(or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-eGFR drugs biochemically converge into MeK-eRK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-eGFR mo Abs together with the various strategies evaluated to prevent, overcame or revert them.

关键词： Metastatic colorectal cancer epidermal growth factor receptor Resistance Mutation KRAS NRAS BRAF PIK

Microcephaly prevalence after the 2015 to 2016 Zika outbreak in Tangará da Serra, Brazil: a population-based study

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Reproductive and Developmental Medicine 2022年第2期6卷 98-103页

作者： Juliana Herrero da Silva Ana Claudia Pereira Tercas-Trettel Juliano Andre Boquett Giovanny Vinicius Araujo Franca Augusto Cesar Cardoso-dos-Santos Marina Atanaka Marcelo Zagonel Oliveira Anna Pires Terra Viviane Karoline Vivi Lucia Andreia Nunes de Oliveira Lucia Schaedler Ronaldo Fernandes Santos Alves Lavinia Schuler-Faccini Prefeitura Municipal de Tangara da Serra Secretaria de SaudeVigilancia EpidemiologicaTangara da SerraBrazil Programa de Pos-Graduacao em Genetica e Biologia Molecular Universidade Federal do Rio Grande do SulPorto AlegreBrazil Universidade do estado de Mato Grosso Tangara da SerraBrazil Programa de Pos-Graduagcao em Saude Coletiva Universidade Federal de Mato GrossoCuiabaBrazil Instituto Nacional de Genetica medica Populacional-INaGeMP Servico de Genetica MedicaHospital de Clinicas de Porto Alegre(HCPA)Porto AlegreBrazil Programa de Pos-Graduacao em Saude da Crianga e do Adolescente Universidade Federal do Rio Grande do SulPorto AlegreBrazil Secretaria de Vigilancia em Saude Ministerio da SaudeBrasiliaBrazil Laboratorio de Visualizacao Avangada e Geoinformatica(VIZLab) Programa de Pos-Graduacao em Computacao AplicadaUniversidade do Vale do Rio dos SinosSao LeopoldoBrazil Programa de Pos-Graduacao em Ciencia da Informacao Universidade Federal do Rio Grande do SulPorto AlegreBrazil clinica Santa Luzia Tangara da SerraBrazil

Objective::Prenatal infection with the Zika virus (ZIKV) can lead to congenital Zika syndrome (CZS), characterized by microcephaly and brain injury. However, there are questions regarding the prevalence of microcephaly/CZS after the ZIKV outbreak in defined geographic areas. This study aimed to identify adverse outcomes in live births of fetuses exposed in utero to the ZIKV, compared to unexposed births, as well as maternal sociodemographic, delivery, and birth characteristics.Methods::Here, we conducted a cross-sectional observational study to investigate the characteristics of all live births in the city of Tangará da Serra, Mato Grosso, Brazil, in 2016, after the outbreak of ZIKV infection in late 2015. All live births of children to women residing in the municipality of Tangará da Serra between January 1 and December 31, 2016, were evaluated, and head circumference was measured at birth and after 24 hours. Children born with microcephaly or a maternal history of confirmed or suspected prenatal ZIKV infection were evaluated by a multidisciplinary team. The outcomes of the exposed and non-exposed children were compared. Prevalence ratios and their respective 95% confidence intervals were calculated for sociodemographic, delivery, and live birth characteristics.Results::Of 1,441 live births, 106 (7.3%) were from mothers with confirmed or highly probable exposure to ZIKV. The prevalence of severe congenital microcephaly (41.7/10,000) in Tangará da Serra in 2016 was ten-fold higher than that in Latin America before 2015.Conclusion::This study may serve as a model to investigate possible outbreaks of infections in a defined geographical space in the future.

关键词： epidemiology Live births Microcephaly Zika virus

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晨间血压升高与皮下小阻力动脉结构

世界核心医学期刊文摘（心脏病学分册） 2007年第12期3卷 62-页

作者： Rizzoni D. Ported e. Platto C. 奚群英 clinica medica Department of Medical and Surgical Sciences University of Brescia Piazza Spedali Civili 1 25100 Brescia Italy

已有研究证实,在高血压患者中血压(BP)晨间升高(MoR)可预测主要心血管事件的发生。以皮下小阻力动脉的中膜与内腔比值(M/L)评估的小阻力动脉结构改变或许也可预测心血管事件。由于增加的M/L可能放大高血压刺激的效果,本研究在一个高血... 详细信息

已有研究证实,在高血压患者中血压(BP)晨间升高(MoR)可预测主要心血管事件的发生。以皮下小阻力动脉的中膜与内腔比值(M/L)评估的小阻力动脉结构改变或许也可预测心血管事件。由于增加的M/L可能放大高血压刺激的效果,本研究在一个高血压患者人群中评估MoR与M/L之间的可能联系。方法:研究纳入64例原发性高血压患者。所有患者均行皮下脂肪活检。

关键词：动脉结构高血压患者

Neoadjuvant treatment:A window of opportunity for nutritional prehabilitation in patients with pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Surgery 2021年第9期13卷 885-903页

作者： Ilaria Trestini Marco Cintoni emanuele Rinninella Futura Grassi Salvatore Paiella Roberto Salvia emilio Bria Carmelo Pozzo Sergio Alfieri Antonio Gasbarrini Giampaolo Tortora Michele Milella Maria Cristina Mele Section of Oncology Department of MedicinePancreas InstituteUniversity of Verona Hospital TrustVerona 37126Italy Scuola di Specializzazione in Scienza dell’Alimentazione Universitàdi Roma Tor VergataRoma 00133Italy UOC Nutrizione clinica Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico A.Gemelli IRCCSRoma 00168Italy Dipartimento di Medicina e Chirurgia Traslazionale UniversitàCattolica del Sacro CuoreRoma 00168Italy General and Pancreatic Surgery Unit Pancreas InstituteUniversity of Verona Hospital TrustVerona 37126Italy Oncologia medica Unit Comprehensive Cancer CenterFondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy Oncologia medica Unit UniversitàCattolica del Sacro CuoreRoma 00168Italy Digestive Surgery Unit and Pancreatic Surgery Gemelli Center Director Fondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy UOC di Medicina Interna e Gastroenterologia Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy UOSD Nutrizione Avanzata in Oncologia Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A Gemelli IRCCSRoma 00167Italy

Patients affected by pancreatic ductal adenocarcinoma(PDAC)frequently present with advanced disease at the time of diagnosis,limiting an upfront surgical approach.Neoadjuvant treatment(NAT)has become the standard of care to downstage non-metastatic locally advanced PDAC.However,this treatment increases the risk of a nutritional status decline,which in turn,may impact therapeutic tolerance,postoperative outcomes,or even prevent the possibility of surgery.Literature on prehabilitation programs on surgical PDAC patients show a reduction of postoperative complications,length of hospital stay,and readmission rate,while data on prehabilitation in NAT patients are scarce and randomized controlled trials are still missing.Particularly,appropriate nutritional management represents an important therapeutic strategy to promote tissue healing and to enhance patient recovery after surgical trauma.In this regard,NAT may represent a new interesting window of opportunity to implement a nutritional prehabilitation program,aiming to increase the PDAC patient’s capacity to complete the planned therapy and potentially improve clinical and survival outcomes.Given these perspectives,this review attempts to provide an in-depth view of the nutritional derangements during NAT and nutritional prehabilitation program as well as their impact on PDAC patient outcomes.

关键词： Pancreatic cancer Neoadjuvant treatment Pancreatic cancer surgery Nutritional status Nutritional prehabilitation Malnutrition

Obesity and weight loss could alter the properties of adipose stem cells?

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World Journal of Stem Cells 2015年第1期7卷 165-173页

作者： Leandra S Baptista Karina R Silva Radovan Borojevic Laboratorio de bioengenharia de tecidos Instituto Nacional de Metrologia Qualidade e Tecnologia (Inmetro) Duque de Caxias 25250-020 Brazil Nucleo Multidisciplinar de Pesquisa em Xerem (Numpex-Bio) Universidade Federal do Rio de Janeiro (UFRJ) Campus de Xerem Rio de Janeiro 21941-590 Brazil Programa de Pos-graduacao em clinica medica Universidade Federal do Rio de Janeiro (UFRJ) Hospital Universitario Clementino Fraga Filho (HUCFF) Rio de Janeiro 21941-590 Brazil

The discovery that adipose tissue represents an interesting source of multipotent stem cells has led to many studies exploring the clinical potential of these cells in cell-based therapies. Recent advances in understanding the secretory capacity of adipose tissue and the role of adipokines in the development of obesity and associated disorders have added a new dimension to the study of adipose tissue biology in normal and diseased states. Subcutaneous adipose tissue forms the interface between the clinical application of regenerative medicine and the establishment of the pathological condition of obesity. These two facets of adipose tissue should be understood as potentially related phenomena. Because of the functional characteristics of adipose stem cells, these cells represent a fundamental tool for understanding how these two facets are interconnected and could be important for therapeutic applications. In fact, adipose tissue stem cells have multiple functions in obesity related to adipogenic, angiogenic and secretory capacities. In addition, we have also previously described a predominance of larger blood vessels and an adipogenic memory in the subcutaneous adipose tissue after massive weight loss subsequent to bariatric surgery(ex-obese patients). Understanding the reversibility of the behavior of adipose stem cells in obeses and in weight loss is relevant to both physiological studies and the potential use of these cells in regenerative medicine.

关键词： Adipose stem cells Subcutaneousadipose tissue Obesity Weight loss Regenerative medicine

对阿根廷感染性心内膜炎流行病学、临床和微生物学特征的全国性调查:eIRA-2研究

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世界核心医学期刊文摘（心脏病学分册） 2006年第6期2卷 29-29页

作者： Ferreiros e. Nacinovich F. Casabé J.H. 黎一兵 eIRA- 2 Investigators Area de Investigacion Y Consejo de Cardiologia Clinica Y Terapeutica Dr. Tiburcio Padilla Sociedad Argentina de Cardiologa Ciudad Autonoma de Buenos Aires Argentina Dr.

Background: This study aimed to determine the epidemiologic, clinical, microbiologic characteristics, and inhospital outcome of infective endocarditis(Ie) in Argentina and compare the results with those of the 1992 Ie national survey. Methods: A prospective, multicenter study was conducted in 82 hospitals representing 16 of 24 provinces of Argentina. Patients with diagnosis of Ie according to the Duke criteria were surveyed during an 18- month period. Results: From 470 surveyed episodes of Ie, 390 cases were classified as definite and 80 as possible Ie. The mean age of the definite Ie cases was 58.5± 17.3 years; male sex, 70.0% ; and male- female ratio, 2.3 ∶ 1. Pathological evidence of Ie was available in 26.2% . There was no previously known heart disease in 35.1% , and the proportion of prosthetic valve Ie was 15.9% . Causative microorganisms were streptococci, 38.3% (Streptococcus viridans 27.0% , Streptococcus bovis 5.2% , others 6.1% ); enterococci, 10.2% ; staphylococci, 36.7% (Staphylococcus aureus 29.8% , coagulase- negative sta- phylococci 6.9% );HACeK group, 6.1% ; fungal, 1.4% ; and polymicrobial, 2.0% . Blood culture results were negative in 10.8% . Surgical treatment was performed in 26.2% , and the overall inhospital mortality was 24.6% . Patients from the 2002 survey were older(58.5± 17.3 vs 51.3± 18.7 years, Pe frequently had underlying heart disease(64.9% vs 55.0% , Pegenerative valve disease(11.5% vs 4.8% , Penital heart disease(9.5% vs 4.2% , Petic valve Ie(15.9% vs 8.5% , Persely, the prevalence of rheumatic valve disease was significantly less than in the 1992 survey(5.4% vs 13.0% , Pe eIRA- 2 survey shows that the clinical profile of Ie has changed in Argentina. Currently, patients with Ie are older and have a higher frequency of underlying heart disease, degenerative valve disease, and prosthetic valve Ie than previously. The incidence of staphylococcal Ie has increased. Inhospital mortality remains hig

关键词：感染性心内膜炎微生物学特征全国性调查流行病学阿根廷凝固酶阴性葡萄球菌临床金黄色葡萄球菌草绿色链球菌院内死亡率