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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

World Journal of Gastroenterology 2024年第7期30卷 759-769页

作者： Maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa anna mrzljak Quirino Lai Department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Surgery Sapienza University of RomeRome 00185Italy Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineZagreb 10000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor ***,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is *** this perspective,metformin is emerging as a molecule of *** studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR *** systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with *** To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of *** A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free *** A total of 13 studies(5674 patients)were included in this *** of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of *** T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS

关键词： Pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

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Are treatment options used for adult-onset type 2 diabetes mellitus(equally)available and effective for children and adolescents?

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World Journal of Diabetes 2024年第4期15卷 623-628页

作者： Nevena Krnic Vibor Sesa anna mrzljak Maja Cigrovski Berkovic Clinics for Pediatrics University Hospital Center ZagrebZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia University of Zagreb School of Medicine Zagreb 10000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

Youth-onset type 2 diabetes mellitus(T2DM),influenced by an increase in obesity,is a rising problem *** mechanisms of this early-onset T2DM include both peripheral and hepatic insulin resistance,along with increa-sed hepatic fasting glucose production accompanied by inadequate first and second-phase insulin ***,the incretin effect is *** initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes ***,immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type,while further therapy adjustments are prone to patients’*** agents with proven glycemic and beyond glycemia benefits,such as Glucagon-like polypeptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors,used in the adult population of T2DM patients,might become increasingly important in the treatment ***,metabolic surgery is an option for markedly obese(body mass index>35 kg/m^(2))children and adolescents suffering from T2DM who have uncontrolled glycemia and/or serious comorbidities when lifestyle and pharmacologic interventions *** this mini-review,we will discuss the potential of treatment options considering new data available from randomized control trials,including individuals with adult-onset type diabetes mellitus.

关键词： Youth-onset type 2 diabetes mellitus Treatment Complications Glucose lowering agents Extra-glycemic benefit

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Immunology demystified: A guide for transplant hepatologists

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World Journal of Transplantation 2024年第1期14卷 48-61页

作者： Iva Kosuta Tomislav Kelava Ana Ostojic Vibor Sesa anna mrzljak Hrvoje Lalic Department of Intensive Care Medicine University Hospital Centre ZagrebZagreb 10000Croatia Department of Physiology School of MedicineUniveristy of ZagrebZagreb 10000Croatia Laboratory for Molecular Immunology Croatian Institute for Brain ResearchZagreb 10000Croatia Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Physiology University of Zagreb School of MedicineZagreb 10000Croatia Laboratory for Cell Biology Croatian Institute for Brain ResearchUniversity of Zagreb School of MedicineZagreb 10000Croatia Department of Laboratory Immunology Clinical Department of Laboratory DiagnosticsUniversity Hospital Center ZagrebZagreb 10000Croatia

Liver transplantation has become standard practice for treating end-stage liver *** success of the procedure relies on effective immunosuppressive medications to control the host's immune *** the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune *** ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic ***,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased *** that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive *** knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

关键词： Liver transplantation Allograft rejection Operational immune tolerance Immune reaction Immunosuppression

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Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

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World Journal of Clinical Cases 2024年第6期12卷 1104-1110页

作者： Nikolina Basic-Jukic Ivana Juric Lea Katalinic Vesna Furic-Cunko Vibor Sesa anna mrzljak Department of Nephrology Arterial HypertensionDialysis and TransplantationUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia

BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains *** To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute *** A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute *** were obtained from hospital electronic medical *** acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal *** Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 *** analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the *** hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical *** included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive *** the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic *** survived without complications with a stable kidney allograft *** Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant *** mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

关键词： Acute pancreatitis COVID-19 Kidney transplant Angiotensin-converting enzyme-2 receptor Immunosuppressive agents

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Key challenges of post-liver transplant weight management

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World Journal of Transplantation 2024年第4期14卷 29-37页

作者： Maja Cigrovski Berkovic ViborŠeša Ivan Balen Quirino Lai Hrvoje Silovski anna mrzljak Department for Sport and Exercise Medicine University of ZagrebFaculty of KinesiologyZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia Department of Gastroenterology and Endocrinology General Hospital“Dr.Josip Bencevic”Slavonski Brod 35000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy Department of Hepatobiliary Surgery and Transplantation University Hospital Center ZagrebZagreb 10000Croatia Department of Medicine University of ZagrebSchool of MedicineZagreb 10000Croatia

Liver transplantation serves as a life-saving intervention for patients with endstage liver disease,yet long-term survival remains a ***-liver transplant obesity seems to have a significant contribution to this challenge and it emerges as a significant risk factor for graft steatosis,metabolic syndrome and denovo malignancy *** review synthesizes current literature on prevalence,risk factors and management strategies for post-liver transplant obesity,emphasizing its impact on graft and patient *** review consultation was conducted in Medline/PubMed,SciELO and EMBASE,with the combination of the following keywords:Weight management,liver transplantation,immunosuppressive therapy,lifestyle interventions,bariatric *** therapy has a significant influence on long-term survival of liver transplant patients,yet it seems to have lesser effect on post-transplant obesity development than previously ***,it significantly contributes to the development of other components of metabolic *** predisposing factors for post-transplant obesity development encompass elevated recipient and donor body mass index,a history of alcoholic liver disease,hepatocellular carcinoma,male gender,the absence of cellular rejection and the marital status of the *** immunosuppressive regimens,pharmacotherapy,lifestyle interventions and bariatric surgery represent key components in mitigating post-transplant obesity and improving long-term survival and quality of life in this group of *** identification and intervention thus hold paramount *** research is warranted to refine optimal management strategies and enhance outcomes in this patient population.

关键词： Weight management Liver transplantation Immunosuppressive therapy Lifestyle interventions Bariatric surgery

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Genitourinary tumors and liver transplantation: A comprehensive review

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World Journal of Transplantation 2024年第3期14卷 52-58页

作者： Vibor Sesa Hrvoje Silovski Nikolina Basic-Jukic Iva Kosuta Maja Sremac anna mrzljak Department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia Department of Hepatobiliary Surgery and Transplantation University Hospital Center ZagrebZagreb 10000Croatia Department of Medicine School of MedicineZagreb 10000Croatia Department of Nephrology Arterial hypertensionDialysis and TransplantationUniversity Hospital Center ZagrebZagreb 10000Croatia Department of Intensive Care Medicine University Hospital Center ZagrebZagreb 10000Croatia

Liver transplantation is as a crucial therapeutic option for patients with end-stage liver disease,but the persistent organ shortage emphasizes a need to explore unconventional donor sources,including individuals with a history of *** review investigates the viability of liver donation from individuals with current or past genitourinary malignancies,focusing on renal,prostate and urinary bladder *** rising incidence of urogenital malignancies among potential donors is thought to result from increasing donor *** of transmission risks reveals low rates of donor-derived cancer transmission,partic-ularly for early-stage renal and prostate *** with a history of genitourinary malignancy pose complex challenges regarding post-transplant immunosuppression and cancer ***,the evidence suggests acceptable outcomes can be achieved with careful patient selection and tailored management *** for pre-transplant evaluation and post-transplant surveillance are discussed,highlighting the need for individualized approaches in this patient *** prospective studies are warranted to refine guidelines and optimize outcomes in liver transplantation for patients with genitourinary malignancies.

关键词： Liver transplantation Genitourinary malignancies Donor-transmitted cancer Malignancy recurrence Immunosuppression

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Diagnosis of West Nile virus infections:Evaluation of different laboratory methods

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World Journal of Virology 2024年第4期13卷 51-61页

作者： Tatjana Vilibic-Cavlek Maja Bogdanic Vladimir Savic Zeljka Hruskar Ljubo Barbic Vladimir Stevanovic Ljiljana Antolasic Ljiljana Milasincic Dario Sabadi Gorana Miletic Ivona Coric anna mrzljak Eddy Listes Giovanni Savini Department of Virology Croatian Institute of Public HealthZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Poultry Center Croatian Veterinary InstituteZagreb 10000Croatia Department of Microbiology and Infectious Diseases with Clinic Faculty of Veterinary Medicine University of ZagrebZagreb 10000Croatia Department of Infectious Diseases Clinical Hospital Center OsijekOsijek 31000Croatia Medical Faculty Josip Juraj Strossmayer University of OsijekOsijek 31000Croatia Department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia Croatian Veterinary Institute Veterinary Institute SplitSplit 21000Croatia OIE Reference Center for West Nile Disease Istituto Zooprofilattico SperimentaleG.CaporaleTeramo 64100Italy

BACKGROUND The diagnosis of West Nile virus(WNV)is challenging due to short-term and low-level viremia,flavivirus cross-reactivity,and long immunoglobulin M(IgM)*** To evaluate different methods for WNV detection[reverse transcription-polymerase chain reaction(RT-PCR),IgM/IgG antibodies,IgG avidity]in serum,cerebrospinal fluid(CSF),and urine samples of patients with confirmed WNV *** The study included patients with confirmed WNV neuroinvasive infection(n=62),asymptomatic WNV seropositive individuals(n=22),and individuals with false-positive WNV IgM antibodies(n=30).WNV RNA was detected using RT-PCR.A commercial ELISA was used to detect WNV IgM/IgG antibodies with confirmation of cross-reactive samples using a virus neutralization test(VNT).IgG-positive samples were tested for IgG *** The WNV-RNA detection rates were significantly higher in the urine(54.5%)/serum(46.4%)than in CSF(32.2%).According to the sampling time,the WNV-RNA detection rates in urine collected within 7 days/8-14/≥15 days were 29.4/66.6/62.5%(P=0.042).However,these differences were not observed in the *** median RT-PCR cycle threshold values were significantly lower in urine(32.5,IQR=28-34)than in CSF(34.5,IQR=33-36).The frequency of positive WNV IgM and IgG significantly differed according to the sampling time in serum but not in *** IgM/IgG antibodies were detected in 84.3/9.3%of serum samples collected within 7 days,100/71.1%of samples collected 8-14,and 100%samples collected after≥15 *** WNV infection was confirmed by low/borderline avidity index(AI)in 13.6%of asymptomatic individuals.A correlation between ELISA and AI was strong negative for IgM and strong positive for *** significant correlation between ELISA IgG and VNT was *** The frequency of WNV RNA and antibody detection depends on the sampling time and type of clinical *** avidity could differentiate recent WNV infections from long-persisting IgM antibo

关键词： West Nile virus Reverse transcription-polymerase chain reaction Serology IgG avidity Cross-reactivity

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Borderline resectable pancreatic cancer and vascular resections in the era of neoadjuvant therapy

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World Journal of Clinical Cases 2021年第20期9卷 5398-5407页

作者： Danko Mikulic anna mrzljak Department of Surgery University Hospital MerkurZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia

While pancreatic cancer is still characterized by early systemic spread and poor outcomes,the treatment of this disease has changed significantly in recent years due to major advancements in systemic therapy and advanced surgical *** use of effective neoadjuvant approaches combined with aggressive surgical operations within a multidisciplinary setting has improved *** resectable pancreatic cancer is characterized by tumor vascular invasion,and is a setting where the combination of potent neoadjuvant chemotherapy and aggressive surgical methods,including vascular resections and reconstructions,shows its full ***,this will lead to improved local control and curative treatment in a number of patients with this aggressive malignancy.

关键词： Pancreatic adenocarcinoma Borderline resectable Neoadjuvant therapy Venous resection Arterial resection Vascular reconstruction

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Hepatotropic viruses:Is Roma population at risk?

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World Journal of Gastroenterology 2021年第2期27卷 143-151页

作者： anna mrzljak Lucija Bajkovec Tatjana Vilibic-Cavlek Department of Gastroenterology University Hospital MerkurZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Department of Medicine County Hospital CakovecCakovec 40000Croatia Department of Virology Croatian Institute of Public HealthZagreb 10000Croatia

Roma people make up a significant ethnic minority in many European countries,with the vast majority living in Central and Eastern *** are a vulnerable population group in social,economic,and political *** migrations,life in segregated communities,substandard housing,poverty,and limited access to quality health care,including low immunization coverage,affect their health status and predispose them to various diseases,including viral *** A,B,and E are highly prevalent among Roma and mainly associated with low socioeconomic *** contrast,hepatitis C does not seem to be more frequent in the Roma *** efforts should be directed towards the implementation of screening programs,preventive measures,and treatment of viral hepatitis in Roma communities throughout Europe.

关键词： Roma population Hepatitis A virus Hepatitis B virus Hepatitis C virus Hepatitis E virus Europe

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Lymphocytic choriomeningitis virus:An under-recognized congenital teratogen

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World Journal of Clinical Cases 2022年第25期10卷 8922-8931页

作者： Thomas Ferenc Mateja Vujica anna mrzljak Tatjana Vilibic-Cavlek Department of Radiology Merkur University HospitalZagreb 10000Croatia Department of Emergency Medicine Institute of Emergency Medicine of Krapina-Zagorje CountyKrapina 49000Croatia Department of Gastroenterology and Hepatology University Hospital Center ZagrebZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Department of Virology Croatian National Institute of Public HealthZagreb 10000Croatia

BACKGROUND Lymphocytic choriomeningitis virus(LCMV)is a neglected rodent-borne arenavirus associated with transplacental transmission and fetal *** To summarize the epidemiological,clinical,and diagnostic features of reported patients with congenital LCMV *** A literature search was conducted in PubMed,Medline,Google Scholar,and *** keywords used were‘congenital lymphocytic choriomeningitis virus,’and 48 studies were *** addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://*** ***).RESULTS The results have shown 27 reports of congenital LCMV infection in 86 patients,with 52.73%of them being *** presented with chorioretinitis(83.53%),hydrocephalus(54.12%),and psychomotor retardation or developmental delay(54.12%).Computed tomography and/or magnetic resonance imaging most often demonstrated ventriculomegaly(74.07%),periventricular calcifications(66.67%),and microcephaly(40%).Most mothers of congenitally infected infants were exposed to rodents during pregnancy,predominantly mice,with flu-like symptoms mainly occurring during the first two trimesters of *** in congenitally infected children was 16.47%.The diagnosis of congenital LCMV infection was confirmed serologically in most patients(86.67%).CONCLUSION LCMV is still an insufficiently recognized fetal teratogen that often leads to long-term neurologic *** need to be familiar with LCMV and its potential teratogenic effect and as well as to effectively differentiate LCMV from other TORCH(T:Toxoplasma gondii,O:Other pathogens,R:Rubella virus,C:Cytomegalovirus,H:Herpes simplex virus)pathogens.

关键词： Lymphocytic choriomeningitis virus Congenital infection Epidemiology Pregnancy TORCH

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