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The use of liquid biopsy in early breast cancer:clinical evidence and future perspectives

Journal of Cancer Metastasis and Treatment 2021年第1期7卷 33-48页

作者： paolo D’Amico Carla Corvaja lorenzo Gerratana Carolina Reduzzi Giuseppe Curigliano Massimo Cristofanilli Division of Hematology and Oncology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoIL 60611USA Division of Early Drug Development for Innovative Therapies IEOEuropean Institute of Oncology IRCCSMilan 20132Italy Department of Oncology and Hemato-Oncology University of MilanoMilan 20122Italy Department of Oncology ASUFCUniversity Hospital of UdineUdine 33100Italy Department of Medicine University of UdineUdine 33100Italy Department of Medical Oncology Centro di Riferimento Oncologico(CRO)IRCCSPordenone 33081Italy

Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is gaining momentum as a diagnostic modality adopted in the clinical management of breast *** studies testing several technologies demonstrated clinical validity and,in some cases,achieved the United States Food and Drug Administration *** initial testing and clinical application of liquid biopsy focused primarily on the diagnosis,while molecular characterization and monitoring of metastatic disease,with larger data from prospective studies,came in the last two *** its role in metastatic setting is thus widely recognized,the current evidence does not provide support for the routine clinical use of liquid biopsy methods for the earlier stage of this *** the relevance of early detection,characterization,and management of breast cancer in the early-stage,this clinical setting is the most suitable to increase the chances for effective treatment selection and improved prognosis,and a better understanding of the main application of liquid biopsy tools in the earlier stage of breast cancer is therefore *** aim of this review is to provide an overview of the clinical evidence and subsequent potential applications of liquid biopsy in early breast cancer,identifying the main existing caveats and the possible future scenarios.

关键词： Liquid biopsy early breast cancer circulating tumor cells circulating tumor DNA clinical trials screening early detection minimal residual disease

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Cell proliferation of esophageal squamous epithelium in erosive and non-erosive reflux disease

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World Journal of Gastroenterology 2011年第40期17卷 4496-4502页

作者： Carlo Calabrese lorenzo Montanaro Giuseppina Liguori Elisa Brighenti Mauela Vici paolo Gionchetti Fernando Rizzello Massimo Campieri Massimo Derenzini Davide Trerè Department of Clinical Medicine University of Bologna 40138 Bologna Italy Department of Experimental Pathology University of Bologna 40138 Bologna Italy Clinical Department Radiological and Histocytopathological Sciences University of Bologna 40138 Bologna Italy

AIM： To elucidate cell proliferation in erosive reflux disease （ERD） and non-erosive reflux disease （NERD）, we evaluated markers in squamous epithelial ***： Thirty-four consecutive patients with gas- troesophageal-reflux-disease-related symptoms （21 NERD and 13 ERD） were evaluated for the enrolment into the study. All patients underwent 24-h pH moni- toring, standard endoscopy, and biopsy for histological evaluation. The expression of cyclins D and A was eval- uated by real-time reverse transcription polymerase chain reaction （RT-PCR） from isolated epithelial cells. In all samples, analysis of the isolated cell population revealed the presence of epithelial cells ***： Real-time RT-PCR showed that, in patientswith ERD, the relative expression of cyclin D1 mRNA in esophageal epithelium was strongly decreased in comparison with NERD patients. The mean value of relative expression of cyclin D1 mRNA in NERD patients was 3.44 ± 1.9, whereas in ERD patients, it was 1.32 ± 0.87 （P = 0.011）. Real-time RT-PCR showed that, in patients with ERD, relative expression of cyclin A mRNA in esophageal epithelium was decreased in comparison with that in NERD patients （2.31 ± 2.87 vs 0.66 ± 1.11）. The mean bromodeoxyuridine labeling index in the NERD patients was 5.42% ± 1.68%, whereas in ERD patients, it was 4.3% ± 1.59%.

关键词： Esophageal cell proliferation Erosive refluxdisease Non-erosive reflux disease Gastroesophagealreflux disease Cyclin A Cyclin D Bromodeoxyuridine

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Ten golden rules for individualized mechanical ventilation in acute respiratory distress syndrome

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Journal of Intensive Medicine 2021年第1期1卷 42-51页

作者： Denise Battaglini Marco Sottano lorenzo Ball Chiara Robba Patricia R.M.Rocco paolo Pelosi Anesthesia and Intensive Care San Martino Policlinico HospitalIRCCS for Oncology and NeuroscienceGenoa 16132Italy Department of Medicine University of BarcelonaBarcelona 08007Spain Department of Surgical Sciences and Integrated Diagnostics University of GenoaGenoa 16126Italy Laboratory of Pulmonary Investigation Carlos Chagas Filho Institute of BiophysicsFederal University of Rio de JaneiroRio de Janeiro 21941-901Brazil

Considerable progress has been made over the last decades in the management of acute respiratory distress syndrome(ARDS).Mechanical ventilation(MV)remains the cornerstone of supportive therapy for ***-protective MV minimizes the risk of ventilator-induced lung injury(VILI)and improves *** parame-ters contribute to the risk of VILI and require careful setting including tidal volume(V_(T)),plateau pressure(P_(plat)),driving pressure(ΔP),positive end-expiratory pressure(PEEP),and respiratory *** of energy and mechanical power allows quantification of the relative contributions of various parameters(V_(T),P_(plat),ΔP,PEEP,respiratory rate,and airflow)for the individualization of MV *** use of neuromuscular blocking agents mainly in cases of severe ARDS can improve oxygenation and reduce asynchrony,although they are not known to confer a survival *** respiratory therapies such as prone positioning,inhaled nitric oxide,and extracorporeal support techniques may be adopted in specific ***,respiratory weaning protocols should also be *** on a review of recent clinical trials,we present 10 golden rules for individualized MV in ARDS management.

关键词： Acute respiratory distress syndrome(ARDS) Protective mechanical ventilation Extracorporeal CO_(2)removal(ECCO_(2)R) Extracorporeal membrane oxygenation (ECMO)

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Disabling portosystemic encephalopathy in a non-cirrhotic patient: successful endovascular treatment of a giant inferior mesenteric-caval shunt via the left internal iliac vein

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World Journal of Gastroenterology 2017年第47期23卷 8426-8431页

作者： Luca de Martinis Gloria Groppelli Riccardo Corti lorenzo paolo Moramarco Pietro Quaretti Pasquale De Cata Mario Rotondi Luca Chiovato Unit of Endocrinology and Internal Medicine University of PaviaICS Maugeri SPA SocietàBenefit Unit of Interventional Radiology Radiology DepartmentIRCCS Fondazione Policlinico San Matteo

Hepatic encephalopathy is suspected in non-cirrhotic cases of encephalopathy because the symptoms are accompanied by hyperammonaemia. Some cases have been misdiagnosed as psychiatric diseases and consequently patients hospitalized in psychiatric institutions or geriatric facilities. Therefore, the importance of accurate diagnosis of this disease should be strongly emphasized. A 68-year-old female patient presented to the Emergency Room with confusion, lethargy, nausea and vomiting. Examination disclosed normal vital signs. Neurological examination revealed a minimally responsive woman without apparent focal deficits and normal reflexes. She had no history of hematologic disorders or alcohol abuse. Her brain TC did not demonstrate any intracranial abnormalities and electroencephalography did not reveal any subclinical epileptiform discharges. Her ammonia level was > 400 mg/d L(reference range < 75 mg/d L) while hepatitis viral markers were negative. The patient was started on lactulose, rifaximin and low-protein *** the basis of the doppler ultrasound and abdomen computed tomography angiography findings, the decision was made to attempt portal venography which confirmed the presence of a giant portal-systemic venous shunt. Therefore, mechanic obliteration of shunt by interventional radiology was performed. As a consequence, mesenteric venous blood returned to hepatopetally flow into the liver, metabolic detoxification of ammonia increased and hepatic encephalopathy subsided. It is crucial that physicians immediately recognize the presence of non-cirrhotic encephalopathy, in view of the potential therapeutic resolution after accurate diagnosis and appropriate treatments.

关键词： Non-cirrhotic patient Portosystemic shunt Hyperammonaemia Interventional radiology Mechanical embolization Encephalopathy

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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

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The Machian Origin of the Centrifugal Force

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Journal of Modern Physics 2012年第9期3卷 1298-1300页

作者： lorenzo Barattini paolo Christillin University of Pisa and I.N.F.N. Pisa Italy

A derivation of the centrifugal force from an effective vector formulation of gravitation is attempted. The centrifugal force appears to be due to a relativistic effect of the counter-rotating Universe. Gravitomagnetic energy effects, a mil-lion times stronger than the self-energy effects responsible for curvature in the GR language, would thus produce the centrifugal acceleration. The Machian picture, already successful in the case of the Coriolis force, gets an additional circumstantial support.

关键词： Centrifugal Force Mach’s Principle

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Thermally reconfigurable quantum photonic circuits at telecom wavelength by femtosecond laser micromachining

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Light(Science & Applications) 2015年第1期4卷 72-78页

作者： Fulvio Flamini lorenzo Magrini Adil S Rab Nicolo Spagnolo Vincenzo D’Ambrosio paolo Mataloni Fabio Sciarrino Tommaso Zandrini Andrea Crespi Roberta Ramponi Roberto Osellame Dipartimento di Fisica-Sapienza Universita di Roma P.le Aldo Moro 5I-00185 RomaItaly Istituto di Fotonica e Nanotecnologie-Consiglio Nazionale delle Ricerche(IFNCNR) P.za Leonardo da Vinci32I-20133 MilanoItaly Dipartimento di Fisica-Politecnico di Milano P.za Leonardo da Vinci32I-20133 MilanoItaly

The importance of integrated quantum photonics in the telecom band is based on the possibility of interfacing with the optical network infrastructure that was developed for classical *** this framework,femtosecond laser-written integrated photonic circuits,which have already been assessed for use in quantum information experiments in the 800-nm wavelength range,have great *** fact,these circuits,being written in glass,can be perfectly mode-matched at telecom wavelength to the in/out coupling fibers,which is a key requirement for a low-loss processing node in future quantum optical *** addition,for several applications,quantum photonic devices must be dynamically ***,we experimentally demonstrate the high performance of femtosecond laser-written photonic circuits for use in quantum experiments in the telecom band,and we demonstrate the use of thermal shifters,which were also fabricated using the same femtosecond laser,to accurately tune such ***-of-the-art manipulation of single-and two-photon states is demonstrated,with fringe visibilities greater than 95%.The results of this work open the way to the realization of reconfigurable quantum photonic circuits based on this technological platform.

关键词： femtosecond laser micromachining integrated quantum photonics thermal shifters tunable optical circuits

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Classifying Cardiac Anomalies in Right and Left Isomerism:Concordant and Discordant Patterns

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Congenital Heart Disease 2023年第1期18卷 97-111页

作者： Lilia Oreto Giuseppe Mandraffino paolo Ciliberti Teresa P.Santangelo Placido Romeo Antonio Celona Placido Gitto lorenzo Galletti Fiore S.Iorio Alfredo Di Pino Aurelio Secinaro paolo Guccione Robert H.Anderson Salvatore Agati Mediterranean Pediatric Cardiology Center Bambino GesùChildren’s HospitalVia SirinaTaorminaItaly Internal Medicine Unit Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly Department of Pediatric Cardiology and Cardiac Surgery Bambino GesùChildren’s HospitalRomaItaly Advanced Cardiovascular Imaging Unit Department of ImagingBambino GesùChildren’s HospitalRomaItaly Radiology Department S.Vincenzo HospitalTaorminaItaly Biosciences Institute Newcastle UniversityNewcastle upon TyneUK

Aims:Evidence is emerging that,in the setting of isomerism,the atrial and bronchial arrangement are not always concordant,nor are these patterns always harmonious with the arrangement of the abdominal *** aimed to evaluate the concordance between these features in a cohort of patients with cardiac malformations in the setting of known isomerism,seeking to determine whether it was feasible to assess complexity on this basis,in this regard taking note of the potential value of bronchial as opposed to appendage *** and Results:We studied 78 patients known to have isomerism of the bronchuses,43 with right and 35 with left *** anatomy could be determined in 49 cases(63%),all but one of these being concordant with bronchial *** assessing abdominal features,in only 59 cases(76%)was splenic morphology in keeping with the thoracic *** expected,right isomerism was associated with greater complexity of cardiac malformations,with an odds ratio of 6.53,with confidence intervals from 2.2–19.3(p<0.001).The odds were slightly decreased with thoraco-abdominal disharmony,when lesions shown to carry higher risk were then found in the setting of left ***:Harmony is excellent between bronchial and appendage isomerism,but less so with the arrangement of the abdominal *** isomerism in our cohort,was indicative of a sixfold increase in intracardiac *** discordance was found between the systems,however,the cardiac anomalies were less typical of the anticipated findings for right *** isomerism of the appendages.

关键词： Isomerism asplenia polysplenia congenital heart disease bronchial isomerism atrial appendages

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Feasibility of cabazitaxel in octogenarian prostate cancer patients

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Current Urology 2023年第3期17卷 153-158页

作者： paolo Tralongo Sebastiano Bordonaro Giuseppe Di lorenzo Ugo De Giorgi NicolòBorsellino Gaetano Facchini Sabrina Rossetti Giuseppe Fornarini Vito Longo Antonino Carmelo Tralongo Francesca Caspani Massimiliano Spada Nicola Calvani paolo Carlini Medical Oncology Unit RAO-Umberto I HospitalSiracusa96100Italy Department of Medicine and Health Sciences‘Vincenzo Tiberio' University of MoliseCampobassoItaly Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori(IRST)IRCCS Meldola(FC)Italy Medical Oncology Unit Ospedale Buccheri La FerlaFatebenefratelliPalermoItaly Medical Oncology Unit Santa Maria delle Grazie di PozzuoliNapoliItaly Departmental Unit of Clinical and Experimental Uro-Andrologic Oncology Istituto Nazionale TumoriIRCCSFondazione G.PascaleNapoliItaly Medical Oncology 1 IRCCSOspedale Policlinico San MartinoGenovaItaly Istituto Tumori Giovanni paoloⅡI.R.C.C.S. BaOspedale di CircoloVareseItaly Medical Oncology Unit ASSTSETTE LAGHIOspedale di CircoloVareseItaly Medical Oncology Unit Fondazione Istituto G.Giglio di CefalùPalermoItaly Medical Oncology Division&Breast Unit Sen.A.Perrino HospitalBrindisiItaly Medical Oncology 1 Istituto Nazionale Tumori Regina ElenaRomaItaly

Background:To evaluate the effectiveness and safety of cabazitaxel in castration-resistant prostate cancer patients aged>80 years,we performed a retrospective study on a sample of patients from 11 Italian cancer *** and methods:Fifty-seven patients aged>80 years were treated with cabazitaxel after previous failure with docetaxel;39 completed a comprehensive geriatric assessment questionnaire(34 fit and 5 vulnerable)and 8 patients(14%)had an Eastern Cooperative Oncology Group performance status(PS)>2,while most had a PS of 0-1(86%).Cabazitaxel was administered at a dose of 25 mg/m^(2)in 30(52%)patients and 20 mg/m^(2)or adapted schedules in 27(48%)*** schedules were adopted mainly in patients>85 years(75%),with a PS>2(87.5%),and those classified as vulnerable(100%).Results:The duration of treatment was 4.8 months and was comparable in all subgroups;disease control rate was reported in 36 patients(63%);prostate-specific antigen response was recorded in 18 patients(31.5%).Median overall survival was 13.1 months regardless of age(85 years),but overall survival was reduced in vulnerable(7.2 months)and PS>2 patients(6.8 months).The most frequently documented grade 3-4 toxicities were neutropenia(14%)and diarrhea(10.5%).Six patients(10.5%)dropped out due to severe ***:Octogenarian patients can be treated with cabazitaxel with reduced doses or alternative schedules that are associated with less toxicity and fewer treatment *** geriatric assessment could facilitate more appropriate patient selection.

关键词： Cabazitaxel Cancer Octogenarian Prostate

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Intestinal ischemic manifestations of SARS-CoV-2:Results from the ABDOCOVID multicentre study

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World Journal of Gastroenterology 2021年第32期27卷 5448-5459页

作者： lorenzo Norsa Pietro Andrea Bonaffini Maja Caldato Cristiana Bonifacio Aurelio Sonzogni Amedeo Indriolo Clarissa Valle Federica Furfaro Alice Bonanomi paolo NiccolòFranco Mauro Gori Veronica Smania Lucia Scaramella Laura Forzenigo Maurizio Vecchi Monica Solbiati Giorgio Costantino Silvio Danese lorenzo D'Antiga Sandro Sironi Luca Elli Department of Pediatric Gastroenterology Hepatology and Transplantation ASST Papa Giovanni XXIIIBergamo 24127Italy Department of Radiology Papa Giovanni XXIII Bergamo University of Milano-BicoccaMilan 20126Italy Fondazione IRCCS Ca’Granda Department of Emergency MedicineOspedale Maggiore PoliclinicoMilano 20122Italy Department of Radiology Humanitas Clinical and Research CenterIRCCSRozzano 20089Italy Department of Pathology ASST Papa Giovanni XXIIIBergamo 24127Italy Department of Gastroenterology and Endoscopy ASST Papa Giovanni XXIIIBergamo 24127Italy IBD Center Humanitas Clinical and Research Center IRCCSHumanitas UniversityRozzano 20089Italy Post-Graduate School of Diagnostic Radiology University of Milano-BicoccaMilano 20126Italy Cardiovascular Department ASST Papa Giovanni XXIIIBergamo 24127Italy Department of Gastroenterology and Endoscopy Fondazione IRCCS Ca'Granda Ospedale Maggiore PoliclinicoMilano 20122Italy Department of Pathophysiology and Transplantation University of MilanMilano 20122Italy Department of Radiology Fondazione IRCCS Ca'Granda Ospedale Maggiore PoliclinicoMilano 20122Italy Fondazione IRCCS Ca’Granda Department of Emergency MedicineOspedale Maggiore PoliclinicoDepartment of Clinical Sciences and Community HealthUniversity of MilanMilano 20122Italy

BACKGROUND Intestinal ischemia has been described in case reports of patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)disease(coronavirus disease 19,COVID-19).AIM To define the clinical and histological,characteristics,as well as the outcome of ischemic gastrointestinal manifestations of SARS-CoV-2 *** A structured retrospective collection was promoted among three tertiary referral centres during the first wave of the pandemic in northern ***,radiological,endoscopic and histological data of patients hospitalized for COVID-19 between March 1st and May 30th were *** diagnosis was established by consecutive analysis of all abdominal computed tomography(CT)scans *** Among 2929 patients,21(0.7%)showed gastrointestinal ischemic manifestations either as presenting symptom or during *** CT showed bowel distention in 6 patients while signs of colitis/enteritis in *** patients presented thrombosis of main abdominal ***,when feasible,confirmed the diagnosis(6 patients).Surgical resection was necessary in 4/21 *** tissue examination showed distinctive features of endothelial inflammation in the small bowel and *** hospital stay was 9 d with a mortality rate of 39%.CONCLUSION Gastrointestinal ischemia represents a rare manifestation of COVID-19.A high index of suspicion should lead to investigate this complication by CT scan,in the attempt to reduce its high mortality *** shows atypical feature of ischemia with important endotheliitis,probably linked to thrombotic microangiopathies.

关键词： Coronavirus COVID-19 Ischemic colitis Small bowel ischemia Endothelial inflammation

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