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Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype

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World Journal of Transplantation 2023年第6期13卷 368-378页

作者： Adam diamond Sunil Karhadkar Kenneth Chavin Serban Constantinescu Kwan N.Lau Oscar Perez-Leal Kerry Mohrien Nicole Sifontis antonio di carlo Department of Pharmacy Temple University HospitalPhiladelphiaPA 19140United States Department of Surgery Temple University HospitalPhiladelphiaPA 19140United States Department of Medicine Temple University School of MedicinePhiladelphiaPA 19140United States Department of Pharmaceutical Sciences Jayne Haines Center for Pharmacogenomics and Drug SafetyTemple University School of PharmacyPhiladelphiaPA 19140United States Department of Pharmacy Practice Temple University School of PharmacyPhiladelphiaPA 19140United States

BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant *** requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 *** who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo *** To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 *** Single-arm,prospective,single-center,open-label,observational study(***:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body *** weight is more than 120%of ideal body weight,an adjusted body weight was *** dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/*** analysis of CYP3A5 genotype was performed at study *** Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d *** adverse events were reported for 13(36%)*** Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release

关键词： Immunosuppression Kidney transplant Dosing Tacrolimus Therapeutic drug monitoring Genotype

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diagnosis of ruptured superior mesenteric artery aneurysm mimicking a pancreatic mass

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World Journal of Gastroenterology 2010年第18期16卷 2298-2301页

作者： Stefano Palmucci Letizia Antonella Mauro Pietro Milone Francesco di Stefano Antonino Scolaro antonio di Cataldo Giovanni carlo Ettorre Department DOGIRA Section of Radiological Sciences"Policlinico-Vittorio Emanuele" University Hospital division of Phlebologic Vascular Surgery Hospital "Garibaldi Nesima" Department of General and Colorectal Surgery "Policlinico-Vittorio Emanuele" University Hospital

Aneurysms and pseudoaneurysms of the superior mesenteric artery are potentially lethal and should be treated as urgently as *** a 52-year-old man with occasional epigastric pain,we accidentally discovered a superior mesenteric artery aneurysm that was ruptured with spontaneous tamponade in the uncinate process and in the head of the *** ruptured aneurysm had a heterogeneous appearance due to its thrombotic and hemorrhagic content,and it simulated a voluminous mass in the head and uncinate process of the pancreas,associated with mild dilatation of the main pancreatic *** advances in multidetector computed tomography and magnetic resonance imaging have enabled radiologists to develop a correct diagnosis of mesenteric aneurysms and pseudoaneurysms of the visceral branches of the abdominal aorta,and to differentiate this diagnosis from that of pancreatic or peripancreatic masses;angiography is currently used to confirm a diagnosis and to develop therapeutic treatments.

关键词： Superior mesenteric artery Magnetic resonance imaging Computed tomography Ruptured aneurysm

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A mutation in the ZNF687 gene that is responsible for the severe form of Paget's disease of bone causes severely altered bone remodeling and promotes hepatocellular carcinoma onset in a knock-in mouse model

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Bone Research 2023年第1期11卷 201-214页

作者： Sharon Russo Federica Scotto di carlo antonio Maurizi Giorgio Fortunato Anna Teti Danilo Licastro Carmine Settembre Tommaso Mello Fernando Gianfrancesco Institute of Genetics and Biophysics“Adriano Buzzati-Traverso” National Research Council of ItalyNaplesItaly Department of Environmental Biological and Pharmaceutical Sciences and Technologies(DiSTABiF)University of Campania Luigi VanvitelliCasertaItaly Department of Biotechnological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly AREA Science Park PadricianoTriesteItaly Telethon Institute of Genetics and Medicine(TIGEM) PozzuoliItaly Gastroenterology Unit Department of Experimental and Clinical Biochemical Sciences“Mario Serio”University of FlorenceFlorenceItaly IRCCS INM Neuromed PozzilliISItaly

Paget’s disease(PDB)is a late-onset bone remodeling disorder with a broad spectrum of symptoms and *** of the most aggressive forms is caused by the P937R mutation in the ZNF687 *** the genetic involvement of ZNF687 in PDB has been extensively studied,the molecular mechanisms underlying this association remain ***,we describe the first Zfp687 knock-in mouse model and demonstrate that the mutation recapitulates the PDB phenotype,resulting in severely altered bone *** microcomputed tomography analysis,we observed that 8-month-old mutant mice showed a mainly osteolytic phase,with a significant decrease in the trabecular bone volume affecting the femurs and the ***,osteoblast activity was deregulated,producing disorganized ***,this phenotype became pervasive in 16-month-old mice,where osteoblast function overtook bone resorption,as highlighted by the presence of woven bone in histological analyses,consistent with the PDB ***,we detected osteophytes and intervertebral disc degeneration,outlining for the first time the link between osteoarthritis and PDB in a PDB mouse *** sequencing of wild-type and Zfp687 knockout RAW264.7 cells identified a set of genes involved in osteoclastogenesis potentially regulated by Zfp687,e.g.,Tspan7,Cpe,Vegfc,and Ggt1,confirming its role in this ***,in this mouse model,the mutation was also associated with a high penetrance of hepatocellular ***,this study established an essential role of Zfp687 in the regulation of bone remodeling,offering the potential to therapeutically treat PDB,and underlines the oncogenic potential of ZNF687.

关键词： RAW264.7 Paget remodeling

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Vascular injury during laparoscopic cholecystectomy:An oftenoverlooked complication

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World Journal of Gastrointestinal Surgery 2023年第3期15卷 338-345页

作者： antonio Pesce Nicolò Fabbri carlo Vittorio Feo Department of Surgery University of FerraraAzienda USL of FerraraAzienda USL of FerraraLagosanto 44023FerraraItaly

Laparoscopic cholecystectomy is one of the most frequently performed procedures in gastrointestinal surgery *** complications due to vascular injuries represent an important cause of morbidity and mortality,especially when facing major bleeding during laparoscopy,where bleeding control can be technically challenging in inexperienced ***,the reported incidence rate of conversion to open surgery due to vascular lesions is approximately 0%-1.9%,with a mortality rate of approximately 0.02%.The primary aim of this article was to perform an up-to-date overview regarding the incidence and surgical management of vascular injuries during laparoscopic cholecystectomy according to the available scientific evidence.

关键词： Laparoscopic cholecystectomy Vascular injury Vascular anomalies Surgical management Specialized hepatobiliary centers

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Parallel pathways:A chronicle of evolution in rectal and breast cancer surgery

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1091-1096页

作者： antonio Pesce NicolòFabbri diletta Iovino carlo Vittorio Feo Unit of General Surgery University of FerraraAzienda USL of FerraraFerrara 44023LagosantoItaly

In this editorial,we have analyzed the historical evolution of rectal and breast cancer surgery,focusing on the progressive reduction of demolitive approaches and the increasing use of more conservative strategies,accompanied by a growing emphasis on perioperative treatments aimed at enhancing surgical *** of these changes have been made possible due to an increased awareness and understanding of oncological diseases and improved perioperative treatments.

关键词： Rectal cancer History Breast surgery Demolitive treatment Conservative surgery

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diabetic foot syndrome:Immune-inflammatory features as possible cardiovascular markers in diabetes

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World Journal of Orthopedics 2015年第1期6卷 62-76页

作者： Antonino Tuttolomondo carlo Maida antonio Pinto dipartimento Biomedico di Medicina Interna e Specialistica U.O.C di Medicina Interna e CardioangiologiaUniversità degli Studi di Palermo

diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. diabetic foot syndrome(DFS), as defined by the World Health Organization, is an "ulceration of the foot(distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection". Pathogenic events able to cause diabetic foot ulcers are *** the commonest causes of this pathogenic pathway it's possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how diabetic patients show a higher mortality rate compared to patients without diabetes and in particular these studies under filled how cardiovascular mortality and morbidity is 2-4 times higher among patients affected by type 2 diabetes mellitus. This higher degree of cardiovascular morbidity has been explained as due to the observed higher prevalence of major cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases, and of prevalence and incidence of cardiovascular and cerebrovascular events in diabetic patients with foot complications. In diabetes a fundamental pathogenic pathway of most of vascular complications has been reported as linked to a complex interplay of inflammatory, metabolic and procoagulant variables. These pathogenetic aspects have a direct interplay with an insulin resistance, subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid disorder. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects as reported by Tuttolomondo et al confirmed the pathogenetic issue of the a "adipo-vascular" axis that may contribute to cardiovascular risk in patients with type 2 diabetes. This "adipo-vascular axis" in patients with type 2 diabetes has been reported as characterized by lower plasma l

关键词： diabetic foot syndrome Inflammation Cytokines Cardiovascular risk Marker

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Minimally invasive surgical approach for abdominoscrotal hydrocele treatment:A case report

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Current Urology 2024年第3期18卷 244-246页

作者： Salvatore Siracusano Martina Monti Igino Andrea Magli Federico Romantini Maria Paola di Bartolomeo antonio Bernardini carlo Vicentini Department of Urology L'Aquila UniversityMazzini HospitalTeramoItaly Department of Radiology Mazzini HospitalTeramoItaly

Abdominoscrotal hydrocele(ASH)is a rare clinical finding comprising fluid collection between the layers of the tunica vaginalis,extending from the scrotum to the abdominal *** present,there is no unique or recommended management for ASH,and different surgical treatments have been *** an open surgical approach being the most common treatment,the use of laparoscopy has also previously been *** most common intraoperative complication is devascularization of the testis due to damage to the spermatic cord,with consequent *** present a case of ASH treated with minimally invasive surgery,consisting of a right inguinotomy with puncture of the ASH by positioning a mono-J stent avoiding spermatic cord dissection and the risk of testis *** of the hydrocelic sac with iodopovidone through a mono-J stent was performed with healing from ASH and preservation of testicular *** months later,magnetic resonance imaging showed the presence of scar tissue replacing the previous ASH cavity.

关键词： Abdominoscrotal hydrocele Inguinotomy Minimally invasive approach Sclerotization

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Immunotherapy for nonalcoholic fatty liver disease-related hepatocellular carcinoma:Lights and shadows

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World Journal of Gastrointestinal Oncology 2022年第9期14卷 1622-1636页

作者： Federico Costante carlo Airola Francesco Santopaolo antonio Gasbarrini Maurizio Pompili Francesca Romana Ponziani Internal Medicine and Gastroenterology-Hepatology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCSRoma 00168Italy Catholic University Largo Francesco Vito 100168 RomaItaly

About one-fourth of adults globally suffer from nonalcoholic fatty liver disease(NAFLD), which is becoming a leading cause of chronic liver disease worldwide. Its prevalence has rapidly increased in recent years, and is projected to increase even more. NAFLD is a leading cause of hepatocellular carcinoma(HCC), the sixth-most prevalent cancer worldwide and the fourth most common cause of cancer-related death. Although the molecular basis of HCC onset in NAFLD is not completely known, inflammation is a key player. The tumor microenvironment(TME) is heterogeneous in patients with HCC, and is characterized by complex interactions between immune system cells, tumor cells and other stromal and resident liver cells. The etiology of liver disease plays a role in controlling the TME and modulating the immune response. Markers of immune suppression in the TME are associated with a poor prognosis in several solid tumors. Immunotherapy with immune checkpoint inhibitors(ICIs) has become the main option for treating cancers, including HCC. However, meta-analyses have shown that patients with NAFLD-related HCC are less likely to benefit from therapy based on ICIs alone. Conversely, the addition of an angiogenesis inhibitor showed better results regarding the objective response rate and progression-free survival. Adjunctive diagnostic and therapeutic strategies, such as the application of novel biomarkers and the modulation of gut microbiota, should be considered in the future to guide personalized medicine and improve the response to ICIs in patients with NAFLD-related HCC.

关键词： Hepatocellular carcinoma Immunotherapy Liver cancer Nonalcoholic fatty liver disease Metabolic dysfunction-associated fatty liver disease Obesity

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Fluorescent cholangiography: An up-to-date overview twelve years after the first clinical application

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World Journal of Gastroenterology 2021年第36期27卷 5989-6003页

作者： antonio Pesce Gaetano Piccolo Francesca Lecchi NicolòFabbri Michele diana carlo Vittorio Feo Department of Surgery Section of General SurgeryOspedale del DeltaAzienda USL of FerraraUniversity of FerraraFerrara 44023Italy Department of Health Sciences University of MilanUnit of Hepato-Bilio-Pancreatic and Digestive SurgerySan Paolo HospitalMilano 20142Italy Department of General Digestive and Endocrine SurgeryUniversity Hospital of StrasbourgIRCADResearch Institute Against Digestive CancerICUBE labPHOTONICS for HealthUniversity of StrasbourgStrasbourg Cedex F-67091France

Laparoscopic cholecystectomy(LC)is one of the most frequently performed gastrointestinal surgeries *** duct injury(Bdi)represents the most serious complication of LC,with an incidence of 0.3%-0.7%,resulting in significant perioperative morbidity and mortality,impaired quality of life,and high rates of subsequent medico-legal *** most cases,the primary cause of Bdi is the misinterpretation of biliary anatomy,leading to unexpected biliary ***-infrared fluorescent cholangiography is widely spreading in clinical practice to delineate biliary anatomy during LC in elective and emergency *** primary aim of this article was to perform an up-to-date overview of the evolution of this method 12 years after the first clinical application in 2009 and to highlight all advantages and current limitations according to the available scientific evidence.

关键词： Laparoscopic cholecystectomy Bile duct injury Biliary anatomy Fluorescent cholangiography Indocyanine green

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Colonoscopic evaluation of hematochezia in low and average risk patients for colorectal cancer:A prospective study

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World Journal of Gastroenterology 2006年第45期12卷 7304-7308页

作者： Puglisi carlo Russo Francesco Paolo Barbera Carmelo Incarbone Salvatore Aprile Giuseppe Bonanno Giacomo Russo antonio Cattedra di Gastroenterologia Università di Catania Azienda Ospedaliero Universitaria Policlinico-Catania Italy

AIM: To relate the endoscopic findings in patients with hematochezia with regard to age in “low and average risk” for colorectal cancer (CRC) and to localize signifi cant lesions in order to identify patients who need sigmoidoscopy or total colonoscopy. METHODS: This prospective study was performed in an open access GI endoscopy unit. Out of 4322 consecutive patients undergoing colonoscopy, 918 reported hema- tochezia. The fi nal study group comprized 180 patients aged below 45 and 237 over 45. Main exclusion criteria were a 1st-degree family history of colorectal carcinoma, patients reporting blood mixed with stools and/or pro- gressive colonic symptoms, or patients who had under- gone colon surgery for neoplastic lesions. RESULTS: Total colonoscopy could be performed in 96% of patients. Abnormal findings were observed in 34.3% of the younger and in 65.7% of the older ones. Findings were the presence of polyps in the distal colon (n = 2) and IBD in the proximal colon (n = 29) in the group of the younger patients, and polyps (n = 15), IBD (n = 13), and carcinoma (n = 6, 4 of the lesions were located proximal to the splenic flexure) in the elderly. Our f indings suggest that the diagnostic potential of total colonoscopy in patients younger than 45 referring scant hematochezia, is not mandatory. By exploring only the distal tract of the colon we have misdiagnosed two cases of IBD located in the ascending colon. In this group of patients additional risk factors must be identifi ed before performing a total colonoscopy. Regarding the patients older than 45 yr, the exploration of the distal colon would have led to our overlooking a carcinoma, two neoplastic polyps and one IBD located in the proximal colon. CONCLUSION: Young patients with scant hematochezia but without risk factors for neoplasia do not need a totalcolonoscopy, whereas is mandatory performing a total colonoscopy in older patients even in the presence of anal pathology.

关键词： Hematochezia Colonoscopy Neoplasia Colonic neoplasia

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