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Targeted NGS analysis reveals a complex genetic background of idiopathic erythrocytosis in a large Venetian family

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Genes & Diseases 2024年第2期11卷 561-563页

作者： Bertozzi Irene Benetti Andrea Regazzo Daniela Polese Francesca Biagetti Giacomo Ceolotto Giulio Randi Maria Luigia First Medical Clinic University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy Transfusion medicine department Ospedale dell'Angelo - Venezia MestreVia Paccagnella 1Venice 30174Italy Emergency medicine University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy

Absolute erythrocytosis,due to an increased production of red blood cells,becomes manifest with hemoglobin(Hb)levels above 165 or 160 g/L or with a hematocrit(HCT)above 51%and 48%in males and females,respectively.1 A minority of patients have polycythemia vera(PV);acquired secondary erythrocytosis frequently occurs due to appropriate or inappropriate erythropoietin(EPO)excess,while congenital secondary erythrocytosis may derive from genetic defects causing tissue hypoxia.Hereditary erythrocytosis occurs in patients with genetic mutations of the oxygen-sensing pathway(VHL,PHD2,_HIF-1-alpha)or the erythropoietin receptor(EPOR)genes.2 Recently,HFE gene variants have been described in sporadic erythrocytoses.3 In a high proportion(about 70%)of patients with erythrocytosis,a specific etiology remains elusive despite extensive testing,and the diagnosis of idiopathic erythrocytosis(IE)is ruled out.

关键词： diagnosis patients congenital

Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis

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World Journal of Gastroenterology 2014年第10期20卷 2555-2563页

作者： Massimo Bolognesi Marco Di Pascoli Alberto Verardo Angelo Gatta department of Internal medicine-dimed University of Padua Azienda Ospedaliera Università di Padova 35128 Padova Italy

Portal hypertension is a clinical syndrome which leads to several clinical complications,such as the formation and rupture of esophageal and/or gastric varices,ascites,hepatic encephalopathy and hepato-renal syndrome.In cirrhosis,the primary cause of the increase in portal pressure is the enhanced resistance to portal outflow.However,also an increase in splanchnic blood flow worsens and maintains portal hypertension.The vasodilatation of arterial splanchnic vessels and the opening of collateral circulation are the determinants of the increased splanchnic blood flow.Several vasoactive systems/substances,such as nitric oxide,cyclooxygenase-derivatives,carbon monoxide and endogenous cannabinoids are activated in portal hypertension and are responsible for the marked splanchnic vasodilatation.Moreover,an impaired reactivity to vasoconstrictor systems,such as the sympathetic nervous system,vasopressin,angiotensinⅡand endothelin-1,plays a role in this process.The opening of collateral circulation occurs through the reperfusion and dilatation of preexisting vessels,but also through the generation of new vessels.Splanchnic vasodilatation leads to the onset of the hyperdynamic circulatory syndrome,a syndrome which occurs in pa-tients with portal hypertension and is characterized by increased cardiac output and heart rate,and decreased systemic vascular resistance with low arterial blood pressure.Understanding the pathophysiology of splanchnic vasodilatation and hyperdynamic circulatory syndrome is mandatory for the prevention and treatment of portal hypertension and its severe complications.

关键词： Portal hypertension Splanchnic flow Splenic circul

Place of baroreceptor activation therapy in the treatment of resistant hypertension

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World Journal of Hypertension 2016年第1期6卷 36-40页

作者： Gian Paolo Rossi Matteo Azzolini Clinica dell’Ipertensione Arteriosa Department of Medicine-DIMED University of Padua

This mini review describes the development of the therapeutic concept of baroreceptor stimulation over the last fifty years alongside the more recent introduction of it for the treatment of drug- resistant hypertension. The pros and cons of this strategy of treatment over renal sympathetic denervation are also discussed in the light of the results of the studies done in the last decade.

关键词： Resistant hypertension Treatment Baroreceptor stimulation Renal denervation

Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications

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World Journal of Cardiology 2015年第10期7卷 609-620页

作者： Giuseppe Maiolino Valeria Bisogni Giacomo Rossitto Gian Paolo Rossi department of medicine - dimed Hypertension Clinic University of Padua

Atherosclerosis manifests itself clinically at advanced stages when plaques undergo hemorrhage and/or rupture with superimposed thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the lipoprotein-associated phospholipase A2(Lp-PLA2), a member of phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory phospholipids, as oxidized low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including lysophosphatidylcholine and oxidized free fatty acids. We herein review the experimental and clinical studies supporting use of Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only Lp-PLA2 activity and mass, but also Lp-PLA2 gene variations and their association with incident coronary artery disease, stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of Lp-PLA2 activity among the biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the LpPLA2 inhibitor darapladib, which seem to challenge the pathogenic role of Lp-PLA2, will also be discussed.

关键词： Lipoprotein-associated phospholipase A2 Atheroscle

Autoimmune gastritis:Pathologist's viewpoint

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World Journal of Gastroenterology 2015年第42期21卷 12179-12189页

作者： Irene Coati Matteo Fassan Fabio Farinati David Y Graham Robert M Genta Massimo Rugge department of medicine (dimed) Surgical Pathology Unit University of Padua department of Surgery Oncology and Gastroenterology Gastroenterology Unit University of Padua department of medicine Veterans Administration Hospital Baylor College of Medicine Houston Miraca Life Sciences Research Institute departments of Pathology and medicine VA North Texas Health Care System and University of Texas Southwestern Medical Center Dallas

Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic(and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and(intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integratingendoscopy, serology, histology and molecular profiling.

关键词： Autoimmune gastritis Metaplasia Carcinoids Operati

MR全小肠成像评分评估幼儿回结肠克罗恩病活动性

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国际医学放射学杂志 2017年第3期 356-356页

作者： F.Pomerri F.Al Bunni M.Zuliani G.Guariso M.Gasparetto B.Giorgi 李安宁 Department of Medicine-DiMED University of Padova

摘要目的确定儿童克罗恩病(Crohn’s disease,CD)病人中MR活动性指标(MR index of activity,MaRIA)和MR全小肠成像评分(MEGS)同儿童CD疾病活动性指标的相关性。方法回顾性分析行MR全小肠成像(MRE)的经证实患有CD的32例儿童(中位年龄14.5... 详细信息

摘要目的确定儿童克罗恩病(Crohn’s disease,CD)病人中MR活动性指标(MR index of activity,MaRIA)和MR全小肠成像评分(MEGS)同儿童CD疾病活动性指标的相关性。方法回顾性分析行MR全小肠成像(MRE)的经证实患有CD的32例儿童(中位年龄14.5岁,18例男性)。对MRE为基础的评分、简化的CD内镜评分(SES-CD)、儿童CD活动性指标(PCDAI)和C反应蛋白(CRP)水平进行相关性分析。基于PCDAI,对具有中度活动性和严重活动性的患儿的全小肠Ma RIA和MEGS进行比较。结果全小肠MaRIA同

关键词：活动性 MRE CD MR 小肠

Renal function and physical fitness after 12-mo supervised training in kidney transplant recipients

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World Journal of Transplantation 2018年第1期8卷 13-22页

作者： Giulio Sergio Roi Giovanni Mosconi Valentina Totti Maria Laura Angelini Erica Brugin Patrizio Sarto Laura Merlo Sergio Sgarzi Michele Stancari Paola Todeschini Gaetano La Manna Andrea Ermolao Ferdinando Tripi Lucia Andreoli Gianluigi Sella Alberto Anedda Laura Stefani Giorgio Galanti Rocco Di Michele Franco Merni Manuela Trerotola Daniela Storani Alessandro Nanni Costa department of Education and Research Isokinetic Medical Group department of Nephrology and Dialysis Morgagni-Pierantoni Hospital department of Biomedical & Neuromotor Sciences University of Bologna Associazione Nazionale Emodializzati Dialisi e Trapianto department of Cardiovascular Sports Medicine Sports medicine ULSS Company 9 Sports medicine Regional Hospital of Bologna department of Nephrology and Dialysis S. Orsola Hospital Sports medicine Unit dimed Department of Medicine University of Padua Sports medicine Regional Hospital of Modena Sports medicine Regional Hospital of Ravenna Sports medicine Regional Hospital of Parma department of Experimental and Clinical medicine School of Sports Medicine University of Florence Sports Medicine Centre Italian National Transplant Centre

AIM To evaluate the effect of a 12-mo supervised aerobic and resistance training, on renal function and exercise capacity compared to usual care recommendations.METHODS Ninety-nine kidney transplant recipients(KTRs) were assigned to interventional exercise(Group A; n = 52) and a usual care cohort(Group B; n = 47). Blood and urine chemistry, exercise capacity, muscular strength, anthropometric measures and health-related quality of life(HRQo L) were assessed at baseline, and after 6 and 12 mo. Group A underwent a supervised training three times per week for 12 mo. Group B received only general recommendations about home-based physical activities.RESULTS Eighty-five KTRs completed the study(Group A, n = 44; Group B, n = 41). After 12 mo, renal function remained stable in both groups. Group A significantly increased maximum workload(+13 W, P = 0.0003), V'O2 peak(+3.1 mL/kg per minute, P = 0.0099), muscular strength in plantar flexor(+12 kg, P = 0.0368), height in the countermovement jump(+1.9 cm, P = 0.0293) and decreased in Body Mass Index(-0.5 kg/m^2, P = 0.0013). HRQo L significantly improved in physical function(P = 0.0019), physical-role limitations(P = 0.0321) and social functioning scales(P = 0.0346). Noimprovements were found in Group B.CONCLUSION Twelve-month of supervised aerobic and resistance training improves the physiological variables related to physical fitness and cardiovascular risks without consequences on renal function. Recommendations alone are not sufficient to induce changes in exercise capacity of KTRs. Our study is an example of collaborative working between transplant centres, sports medicine and exercise facilities.

关键词： Kidney transplant recipients Renal function Supervised exercise Aerobic exercise Muscle strength

Nrf2 and Her3 co-expression in cholangiocarcinoma:Possible biological pathways for potential therapeutic approach

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 317-321页

作者： Paola Parente Valentina Angerilli Giuseppe Zamboni Angelo Sparaneo Fabiola Fiordelisi Leonarda Di Candia Matteo Fassan Paolo Graziano Pathology Unit Fondazione IRCCS Casa Sollievo della Sofferenza71013San Giovanni Rotondo(Foggia)Italy department of medicine(dimed) Surgical Pathology UnitUniversity of Padua35128Padua(Padua)Italy Pathology Unit IRCCS Ospedale Sacro Cuore Don Calabria37024Negrar(Verona)Italy Laboratory of Oncology Fondazione IRCCS Casa Sollievo della Sofferenza71013San Giovanni Rotondo(Foggia)Italy Veneto Institute of Oncology IOV-IRCCS 35124Padua(Padua)Italy

To the Editor:Cholangiocarcinomas(CCAs)are heterogeneous group of malignancies,encompassing intrahepatic CCA(iCCA),and extrahepatic CCA(eCCA);they are also classified into common hepatic duct cholangiocarcinoma(CHDCCA),choledocus extrapancreatic cholangiocarcinoma(EPCCA)and choledocus intrapancreatic cholangiocarcinoma(IPCCA)and,finally,gallbladder carcinoma(GBCCA).CCAs are relatively uncommon but.

关键词： carcinoma gallbladder Nrf2

HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice

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World Journal of Gastroenterology 2016年第26期22卷 5879-5887页

作者： Federica Grillo Matteo Fassan Francesca Sarocchi Roberto Fiocca Luca Mastracci department of Surgical and Diagnostic Sciences Pathology Unit University of Genoa 16132 Genoa Italy Institute for Research and Cure of Cancer (IRCCS) S. Martino-IST University Hospital 16132 Genoa Italy department of medicine (dimed) Surgical Pathology Unit University of Padua 35121 Padua Italy

HER2 is overexpressed in approximately 10%-20% of gastric and gastroesophageal junction carcinomas. In these types of cancer, accurate assessment of HER2 status is mandatory, for selecting patients who may benefit from targeted therapies with anti-HER2 drugs such as Trastuzumab. This manuscript focuses on HER2 in gastric carcinogenesis, on optimal evaluation of HER2 and on the possible causes which may contribute to inaccurate HER2 evaluation. Similarly to breast cancer HER2 evaluation, standardization of HER2 testing in gastric cancer is necessary in diagnostic practice. The three principle aspects which require consideration are:(1) the choice of sample with regards to cancer morphology- intestinal vs diffuse areas;(2) the choice of scoring criteria- use of HER2 scoring criteria specific for gastric cancer; and(3) the choice of HER2 evaluation methods- use of an algorithm in which both immunohistochemistry and in situ hybridization play a role. Problematic issues include:(1) pre-analytic variables with particular emphasis on fixation;(2) recommended methodology for HER2 assessment(immunohistochemistry vs in situ hybridization);(3) HER2 heterogeneity both within the primary tumor and between primary tumor and metastases;(4) reliability of biopsies in HER 2 evaluation; and(5) quantity of sample(FFPE blocks from surgical specimens or endoscopic biopsies) necessary for an adequate assessment.

关键词： Gastric cancer HER2 Heterogeneity Immunohistochemistry FISH