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Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma:A systematic review and meta-analysis

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World Journal of Diabetes 2023年第8期14卷 1289-1300页

作者： Maja Cigrovski Berkovic Francesco Giovanardi Anna Mrzljak Quirino Lai department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia department of Medicine School of MedicineZagreb 10000Croatia

BACKGROUND Hepatocellular carcinoma(HCC)is among the commonest malignancies associated with significant cancer-related *** identification of chemopreventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is ***,a first-line agent used in the treatment of type 2 diabetes mellitus(T2DM),has been associated with inhibition of HCC *** To determine whether metformin can prevent adverse events(i.e.,death,tumor progression,and recurrence)after any HCC treatment in T2DM *** A systematic review of the published literature was undertaken focused on the role of metformin on outcomes in patients with T2DM and HCC receiving any tumor therapy.A search of the PubMed and Cochrane Central Register of Controlled Trials Databases was *** A total of 13 studies(n=14886 patients)were included in this *** regard to the risk of death,a decreased risk was reported in cases receiving metformin,although this decrease was not statistically significant[odds ratio(OR)=0.89,P=0.42].When only patients treated with curative strategies were considered,a more marked correlation between metformin and favorable cases was reported(OR=0.70,P=0.068).When analyzing palliative treatment,there was no statistical significance in terms of the correlation between metformin and favorable cases(OR=0.74,P=0.66).As for the risks of progressive disease and recurrence,no obvious correlation between metformin use and reduced risk was *** sub-analyses were performed for patients from different regions,the results for patients from Eastern countries showed a tendency for decreased risk of death in T2DM cases receiving metformin(OR=0.69,P=0.17),but the same was not seen in patients from Western countries(OR=1.19,P=0.31).CONCLUSION Metformin failed to show a marked impact in preventing adverse effects after HCC treatment.A trend was reported in T2DM cases receiving curative therapies in relation to the ri

关键词： Hepatocellular carcinoma Metformin Type 2 diabetes mellitus Death Recurrence Progression Treatment

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Coagulation and Endothelial Dysfunction Associated with NAFLD:Current Status and Therapeutic Implications

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 339-355页

作者： Doris Ogresta Anna Mrzljak Maja Cigrovski Berkovic Ines Bilic-Curcic Sanja Stojsavljevic-Shapeski Lucija Virovic-Jukic department of Gastroenterology and Hepatology Sestre Milosrdnice University Hospital CenterZagrebCroatia Depart-ment of Gastroenterology and Hepatology University Hospital Center ZagrebZagrebCroatia department of Medicine University of ZagrebSchool of MedicineZagrebCroatia department for Endocrinology Diabetes and PharmacologyUniversity Hospital DubravaZagrebCroatia department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of Zagreb department of Pharmacology Faculty of MedicineUniversity of JJ StrossmayerOsijekCroatia department of Diabetes Endocrinology and Metabolism DisordersUniversity Hospital OsijekOsijekCroatia

Non-alcoholic fatty liver disease(NAFLD)is closely related to insulin resistance,type 2 diabetes mellitus,and *** is nowadays considered a multisystem disease with a strong association with cardiovascular disease and arterial hypertension,which interfere with changes in the coagulation *** disorders are common in patients with hepatic impairment and are dependent on the degree of liver *** with NAFLD may have preserved overall hemostatic profile,but many studies suggest a trend toward a procoagulant *** state in NAFLD patients may even induce progression of hepatic *** dysfunction is present in the systemic and portal vein circulation in NAFLD patients,and platelets are being recognized as modulators of liver diseases through various *** a literature review,we discuss possible disorders in the coagulation cascade and fibrinolysis,endothelial dysfunction,and platelet abnormalities in patients with *** the processes and mechanisms involved in the hemostatic abnormalities associated with NAFLD,directly related to liver disease or indirectly related through inflam-matory processes and metabolic disorders,several potential therapeutic targets have been identified and reviewed here.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Insulin resistance Coagulation Endothelial dysfunction Platelet dysfunction Thrombosis

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Malignant insulinoma:Can we predict the long-term outcomes?

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World Journal of Clinical Cases 2022年第16期10卷 5124-5132页

作者： Maja Cigrovski Berkovic Monika Ulamec Sonja Marinovic Ivan Balen Anna Mrzljak department of Endocrinology DiabetesMetabolism and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia department of Pathology and Cytology“Ljudevit Jurak” University Hospital Center“Sestre milosrdnice”Zagreb 10000Croatia Scientific Group for Research on Epigenetic Biomarkers and department of Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia Laboratory for Personalized Medicine Division of Molecular MedicineRudjer Boskovic InstituteZagreb 10000Croatia department of Gastroenterology and Endocrinology General Hospital“Dr.Josip Bencevic”Slavonski Brod 35000Croatia department of Gastroenterology and Hepatology UHC ZagrebZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia

Insulinomas are the most frequent type of functional pancreatic neuroendocrine tumors with a variety of neuroglycopenic and autonomic symptoms and welldefined diagnostic criteria;however,prediction of their clinical behavior and early differentiation between benign and malignant lesions remain a *** comparative studies between benign and malignant cases are limited,suggesting that short clinical history,early hypoglycemia during fasting,high proinsulin,insulin,and C-peptide concentrations raise suspicion of ***,malignant tumors are larger with higher mitotic count and Ki-67 proliferative activity,but there are no accurate histological criteria to distinguish benign from malignant *** signaling pathways have been suggested to affect the pathophysiology and behavior of insulinomas;however,our knowledge is limited,urging a further understanding of molecular ***,there is a need for the identification of reliable markers of metastatic disease that could also serve as therapeutic targets in patients with malignant *** opinion review reflects on current gaps in diagnostic and clinical aspects related to the malignant behavior of insulinoma.

关键词： Pancreatic neuroendocrine tumor Malignant insulinoma Resection Liver Transplantation

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Post-transplant diabetes mellitus and preexisting liver disease-a bidirectional relationship affecting treatment and management

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World Journal of Gastroenterology 2020年第21期26卷 2740-2757页

作者： Maja Cigrovski Berkovic Lucija Virovic-Jukic Ines Bilic-Curcic Anna Mrzljak department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Clinical Hospital Dubrava Zagreb 10000Croatia department of Pharmacology Faculty of MedicineUniversity of J.J.Strossmayer OsijekOsijek 31000Croatia School of Medicine University of ZagrebZagreb 10000Croatia department of Medicine Division of Gastroenterology and HepatologySisters of Charity University HospitalZagreb 10000Croatia

Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related *** 2 DM(T2DM)is a wellrecognized risk factor for chronic liver disease and vice-versa,DM may develop as a complication of cirrhosis,irrespective of its *** transplantation(LT)represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease(NAFLD),which represents a hepatic manifestation of metabolic syndrome and a common complication of *** metabolic risk factors including immunosuppressive drugs,can contribute to persistent or de novo development of DM and NAFLD after LT.T2DM,obesity,cardiovascular morbidities and renal impairment,frequently associated with metabolic syndrome and NAFLD,may have negative impact on short and long-term outcomes following *** treatment of DM in the context of chronic liver disease and post-transplant is challenging,but new emerging therapies such as glucagon-like peptide-1 receptor agonists(GLP-1RAs)and sodium–glucose cotransporter 2 inhibitors(SGLT2i)targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.

关键词： Diabetes mellitus Liver transplantation Non-alcoholic fatty liver disease Metabolic syndrome Insulin-resistance Glucagon-like peptide-1 receptor agonists Sodium–glucose cotransporter 2 inhibitors

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How far along are we in revealing the connection between metformin and colorectal cancer?

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World Journal of Gastroenterology 2021年第14期27卷 1362-1368页

作者： Maja Cigrovski Berkovic Danko Mikulic Ines Bilic-Curcic Anna Mrzljak department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Clinical Hospital Dubrava Zagreb 10000Croatia department of Surgery Merkur University HospitalZagreb 10000Croatia department of Pharmacology Faculty of MedicineUniversity of J.J.Strossmayer OsijekOsijek 31000Croatia Clinical Hospital Center Osijek Osijek 31000Croatia department of Medicine Merkur University HospitalSchool of MedicineZagreb 10000Croatia

Colorectal cancer(CRC)is among the most prevalent cancers worldwide,and its prevention and reduction of incidence is *** presence of diabetes has been associated with a 30%increased risk of CRC,likely through the mechanism of hyperinsulinemia,which promotes tumorigenesis via the insulin receptor in the epithelium or by insulin-like growth factor pathways,inflammation,or adipokines,inducing cancer cell proliferation and cancer ***,the first-line agent in treating type 2 diabetes,has a chemopreventive role in CRC ***,preclinical studies suggest synergistic effects of metformin with oxaliplatin in inhibiting in vitro models of colon *** preclinical studies on the post diagnostic use of metformin were promising and suggested its synergistic effects with chemotherapy,the data on the possible effects of metformin after surgery and other CRC treatment in the clinical setting are less conclusive,and randomized controlled trials are still lacking.

关键词： Metformin Type 2 diabetes mellitus Colorectal cancer Chemoprevention Recurrence-free survival Surgery

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Shifting perspectives-interplay between non-alcoholic fatty liver disease and insulin resistance in lean individuals

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World Journal of Hepatology 2021年第1期13卷 80-93页

作者： Ines Bilic-Curcic Maja Cigrovski Berkovic Lucija Virovic-Jukic Anna Mrzljak department of Pharmacology Faculty of MedicineUniversity of J.J.Strossmayer OsijekOsijek 31000Croatia Clinical Hospital Center Osijek Osijek 31000Croatia department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Clinical Hospital Dubrava Zagreb 10000Croatia department of Medicine Division of Gastroenterology and HepatologySisters of Charity University HospitalZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia department of Medicine Merkur University HospitalZagreb 10000Croatia

Non-alcoholic fatty liver disease(NAFLD)has become a significant public health burden affecting not only obese individuals but also people with normal *** opposed to previous beliefs,this particular subset of patients has an increased risk of all-cause mortality and worse outcomes than their obese *** development of NAFLD in lean subjects seems to be interconnected with metabolic phenotype,precisely visceral fat tissue,sarcopenia,and insulin ***,we summarize available data focusing on the co-dependent relationship between metabolic phenotype,insulin resistance,and development of NAFLD in lean individuals,suggesting more appropriate tools for measuring body fat distribution for the screening of patients at risk.

关键词： Non-alcoholic fatty liver disease Metabolic phenotype Lean individuals Insulin resistance Visceral fat tissue Sarcopenia

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Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor

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World Journal of Diabetes 2021年第7期12卷 932-938页

作者： Jelena Marinkovic-Radosevic Maja Cigrovski Berkovic Egon Kruezi Ines Bilic-Curcic Anna Mrzljak department of Endocrinology Diabetes and MetabolismSisters of Charity Clinical Hospital CentreZagreb 10000Croatia department of Endocrinology DiabetesMetabolism and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia department of Gynecology and Obstetrics Sisters of Charity Clinical Hospital CentreZagreb 10000Croatia department of Pharmacology Faculty of MedicineUniversity of J.J.Strossmayer OsijekOsijek 31000Croatia Clinical Hospital Center Osijek Osijek 31000Croatia School of Medicine University of ZagrebZagreb 10000Croatia department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia

Polycystic ovary syndrome(PCOS)is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences.A plethora of symptoms and their severity differentiate on an individual level,giving the syndrome numerous *** to menstrual cycle abnormalities,women suffer from irregular menstrual bleeding,difficulty in conception,and ***,the risk of pregnancy complications such as gestational diabetes mellitus,hypertensive disorders of pregnancy,and preterm birth are higher in women with PCOS than in the general ***,women with PCOS have comorbidities such as dyslipidemia,obesity,glucose intolerance or diabetes type 2,non-alcoholic fatty liver disease,and metabolic syndrome,which all influence the treatment *** insulinsensitizing agents,although good for some of the metabolic derangements,do not offer long-term cardiovascular benefits;therefore,new treatment options are of paramount ***-glucose co-transporter-2(SGLT-2)inhibitors,a new class of antidiabetic agents with beneficial cardiovascular,bodyweight,and antihyperglycemic effects,although not approved for the treatment of PCOS,might be an attractive therapeutic addition in the PCOS ***,recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with *** is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic,reproductive,and psychological consequences.

关键词： Polycystic ovary syndrome Sodium-glucose co-transporter-2 inhibitors Metabolic risk Cardiovascular risk Metabolic syndrome Insulin resistance Obesity Type 2 diabetes mellitus Dyslipidemia

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Application of computed tomography in paleoanthropological research

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Progress in Natural Science:Materials International 2009年第8期19卷 913-921页

作者： Lynne A. Schepartz department of anthropology Florida State University Tallahassee FL 32306-7772 USA

Hominin fossils are the most important materials for exploring questions about human origins and evolution. Because human fossils are very rare, it is impossible to use highly destructive techniques in order to study their morphology. Traditional analyses can only rely on the information gained from the study of the external morphology of specimens, and these approaches limited the study of human evolution. The application of computed tomography (CT) has facilitated major developments in paleoanthropology. To date, few studies on Chinese hominin fossils have used CT scanning methodology, but this is rapidly changing. In order to better understand the application of CT methodology in paleoanthropology, we review the applications of CT scanning on hominin fossils throughout the world. Studies examined include virtual fossil reconstruction, the use of endocasts to elucidate brain morphology, biomechanical analyses of bone distribution, imaging of mummies and research on early human health, and skeletal and dental microanatomical research.

关键词： Paleoanthropology Hominin fossil CT 3D reconstruction Virtual anatomy

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Effect of COVID-19 on management of type 1 diabetes:Pushing the boundaries of telemedical healthcare

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World Journal of Diabetes 2021年第6期12卷 780-785页

作者： Ines Bilic Curcic Maja Cigrovski Berkovic Tomislav Kizivat Silvija Canecki Varzic Robert Smolic Martina Smolic department of Endocrinology University Hospital OsijekOsijek 31000Croatia department of Pharmacology Faculty of Medicine OsijekOsijek 31000Croatia department of Endocrinology DiabetesMetabolism and Clinical PharmacologyUniversity Hospital DubravaZagreb 10000Croatia department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia Clinical Institute of Nuclear Medicine and Radiation Protection University Hospital OsijekOsijek 31000Croatia department of Nuclear Medicine and Oncology Faculty of Medicine OsijekOsijek 31000Croatia department of Internal Medicine Family Medicineand HistoryFaculty of Medicine OsijekOsijek 31000Croatia department of Pathophysiology Faculty of Medicine OsijekOsijek 31000Croatia department of Pathophysiology Physiology and ImmunologyFaculty of Dental Medicine and HealthOsijek 31000Croatia department of Pharmacology and Biochemistry Faculty of Dental Medicine and HealthOsijek 31000Croatia

The new coronavirus disease 2019(COVID-19)pandemic posed a great burden on health care systems worldwide and is an enormous and real obstacle in providing needed health care to patients with chronic diseases such as *** to COVID-19,there have been great advances in technology used for management of type 1 diabetes,primarily insulin pumps,sensors,integrated and closed loop systems,ambulatory glucose profile software,and smart phone apps providing necessary essentials for telemedicine implementation right at the beginning of the COVID-19 *** results of these remote interventions are reassuring in terms of glycemic management and hemoglobin A1c ***,data on long-term outcomes and cost reductions are missing as well as proper technical infrastructure and government health policy support.

关键词： Diabetes management Telemedicine COVID-19 Diabetes type 1

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Glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors combination—are we exploiting their full potential in a real life setting?

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World Journal of Diabetes 2020年第11期11卷 540-552页

作者： Maja Cigrovski Berkovic Ines Bilic-Curcic Tomislav Bozek Davorka Herman Mahecic Sanja KlobucarMajanovic Silvija Canecki-Varzic Jelena Andric Srecko Marusic Anna Mrzljak Faculty of Medicine J.J.Strossmayer University OsijekOsijek 31000Croatia department for Endocrinology Diabetes and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia department of kinesiological anthropology and methodology Faculty of KinesiologyUniversity of ZagrebZagreb 10000Croatia department of Endocrinology and Metabolism Disorders Clinical Hospital CenterOsijek 31000Croatia University Clinic for Diabetes“Vuk Vrhovac” Merkur University HospitalZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia department for Endocrinology Diabetes and MetabolismUniversity Hospital Centre“Sestre milosrdnice”Zagreb 10000Croatia department for Endocrinology Diabetes and MetabolismUniversity Hospital Centre RijekaSchool of MedicineUniversity of Rijeka51000 RijekaCroatia department of Medicine Merkur University HospitalSchool of MedicineUniversity of ZagrebZagreb 10000Croatia

BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)and cardiovascular event *** patients with type 2 diabetes,the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems *** To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and *** We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with(1)GLP-1RA on top of SGLT-2i,(2)SGLT-2i on top of GLP-1RA compared to(3)simultaneous addition of both *** primary study endpoint was the proportion of participants with HbA1c<7.0%and/or 5%bodyweight *** outcomes included changes in fasting plasma glucose(FPG),prandial plasma glucose,lowdensity lipoprotein cholesterol,estimated glomerular filtration rate(eGFR),and cardiovascular(CV)incidents assessment over a follow-up period of 12 *** The majority of patients were over 65-years-old,had diabetes duration for more than 10 *** initial body mass index was 39.41±5.49 kg/m2 and HbA1c 8.32±1.26%.Around half of the patients in all three groups achieved target HbA1c below 7%.A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination *** number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group(P=0.021),and 5%weight loss was dominantly achieved in the simultaneous therapy group(P=0.044).A composite outcome(reduction of HbA1c below 7%(53 mmol/mol)with 5%weight loss)was achieved in 32.3%of total patients included in the *** 18.2%of patients attained composite outc

关键词： Sodium/glucose cotransporter-2 inhibitors Glucagon-like-1 receptor agonists Type 2 diabetes mellitus Body weight Glycemic control Cardiovascular complications

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