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Managing end-stage carcinoid heart disease:A case report and literature review

World Journal of Gastrointestinal Oncology 2024年第3期16卷 1076-1083页

作者： Nikola Bulj Vedran Tomasic maja Cigrovski Berkovic Department of Cardiology University Hospital Centre“Sestre Milosrdnice“Zagreb 10000Croatia Division of Gastroenterology Department of Internal MedicineUniversity Hospital Centre“Sestre Milosrdnice”Zagreb 10000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of life.Cardiovascular complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic disease.CASE SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases.During the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to follow-up.After 10 years,he presented to the emergency room with signs and symptoms of right-sided heart failure.Panneuroendocrine markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic metastases.Computed tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis.Furthermore,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart disease.The patient was not a candidate for valve replacement.He started octreotide acetate treatment,and the dose escalated to 80 mg IM monthly.Although biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart failure.Carcinoid heart disease and tumor burden are major prognostic factors of poor survival.Therefore,they must be actively sought by avai

关键词： Gastroenteropancreatic neuroendocrine neoplasms Carcinoid syndrome Carcinoid heart disease Diagnosis Treatment Case report

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Challenges and pitfalls of youth-onset type 2 diabetes

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World Journal of Diabetes 2024年第5期15卷 876-885页

作者： Lavinia La Grasta Sabolic Sanda Marusic maja Cigrovski Berkovic Department of Pediatric Endocrinology and Diabetology University Hospital Centre Sestre MilosrdniceZagreb 10000Croatia School of Medicine Catholic University of CroatiaZagreb 10000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

关键词： Youth-onset type 2 diabetes mellitus Insulin resistance Beta cell failure Risk factors Therapy Complications

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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 worldwide.Pathophysiological 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 secretion.Moreover,the incretin effect is reduced.The initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes mellitus.Therefore,immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type,while further therapy adjustments are prone to patients’pheno-type.New 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 armamentarium.Moreover,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 fail.In 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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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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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 progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective 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 phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM 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 pNET.METHODS 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 survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis 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 pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies wi

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

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Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

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World Journal of Clinical Cases 2024年第7期12卷 1200-1204页

作者： Ana Majic Tengg maja Cigrovski Berkovic Ivan Zajc Ivan Salaric Danko Müller Iva Markota Department of Endocrinology DiabetesMetabolic Diseases and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia Department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Oral Surgery Clinical Hospital DubravaZagreb 10000Croatia University of Zagreb School of Dental Medicine Zagreb 10000Croatia Clinical Department of Pathology and Cytology Clinical Hospital DubravaZagreb 10000Croatia

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium homeostasis.Most commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and hypercalcemia.Brown tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical practice.The tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic mass.Furthermore,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone lesion.The diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and PTH.Although when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic tumors.Treatment of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical intervention.However,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

关键词： Brown tumor Hyperparathyroidism Lytic bone lesions Giant cell tumor

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Splenic hamartomas in children

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World Journal of Clinical Cases 2024年第11期12卷 1909-1917页

作者： maja Milickovic Petar Rasic Sofija Cvejic Dejana Bozic Djordje Savic Tanja Mijovic Sava Cvetinovic Slavisa M Djuricic Department of Abdominal Surgery Mother and Child Health Care Institute of Serbia"Dr.Vukan Cupic"Belgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia Department of Radiology The Children’s University HospitalBelgrade 11000Serbia Department of Clinical Pathology Mother and Child Health Care Institute of Serbia"Dr.Vukan Cupic"Belgrade 11000Serbia Faculty of Medicine University of Banja LukaBanja Luka 78000Bosnia and Herzegovina

Splenic hamartomas(SHs)are uncommon,benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images,at surgery,or at autopsy.Since the first case description,in 1861,less than 50 pediatric SH cases have been reported in the literature.In this article,we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH.These lesions in children were shown to cause symptoms more often than in the adult population.The observed SH sizes in children ranged from a few millimeters to 18 cm,and the symptomatic lesions were mostly larger or multiple.The most common clinical finding was splenomegaly.Signs of hypersplenism were present in children with a single SH larger than 4.5 cm(diameter range:4.5-18.0 cm)and in those with multiple hamartomas,ranging from a few millimeters to 5 cm.Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia,thrombocytopenia,or pancytopenia.Other symptoms and signs included abdominal pain,recurrent infections,fever,night sweats,lethargy,growth retardation,and weight loss.The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach.However,the final diagnosis of SH relies on histopathological evaluation.Surgery,including total or partial splenectomy(PS),is the mainstay of SH management.Milickovic M et al.Splenomas in children WJCC https://*** 1910 April 16,2024 Volume 12 Issue 11 Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH.In the majority of pediatric patients with symptomatic SH,resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.

关键词： Splenic hamartoma Pediatric Splenoma Clinical features Radiological features Histopathology Treatment

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Review of EU projects with a focus on environmental quality: Innovation, eco-innovation, and circular-economy elements

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International Journal of Innovation Studies 2024年第1期8卷 1-12页

作者： Jana Hojnik Mitja Ruzzier maja Konecnik Ruzzier Boris Sucic Brandon Soltwisch Matej Rus University of Primorska Faculty of ManagementIzolska Vrata 26000KoperSlovenia University of Ljubljana School of Economics and BusinessKardeljeva Ploscad 171000LjubljanaSlovenia Jozef Stefan Institute Energy Efficiency CentreJamova 391000LjubljanaSlovenia Tulane University Freeman School of Business6823 St Charles AveNew OrleansLA 70118USA University of Maribor Faculty of Economics and BusinessRazlagova 142000MariborSlovenia

The primary objective of this study is to delve into transnational projects conducted between 2014 and 2020,with a strong emphasis on environmental quality.Our focus is directed toward projects that encompass either eco-innovation or feature elements intrinsic to a circular economy.To achieve this goal,we introduce a pioneering analytical framework tailored to dissect transnational projects,which intricately interweaves the diverse dimensions of environmental quality and innovation,facilitating a comparative assessment across various program classifications.Our approach aligns with the overarching mission of the four flagship initiatives,in which we evaluate the combined impacts on sustainability and innovation.This evaluation considers three fundamental factors:(1)resource allocation,(2)innovation type,and(3)infusion of eco-innovation or circular economy elements.Our methodology unfolds through a systematic,step-by-step progression.First,we meticulously handpick programs,specifically Interreg,Horizon,and Life projects,within the scope of TSG3(Environmental Quality).Each of these programs corresponds to one of the following four flagship initiatives:(1)overseeing and managing marine species,(2)fostering sustainable development in coastal and maritime zones,(3)safeguarding and elevating natural habitats and terrestrial ecosystems,and(4)formulating transnational contingency strategies for maritime accidents.Through an exhaustive review,we identify projects that either directly or indirectly champion eco-innovation or other facets of the circular economy.Concurrently,we uncover broader manifestations of innovation,eco-innovation,and circular economy principles.Employing the Oslo Manual as a guide,we methodically categorize these innovations into the product,process,organizational,and marketing domains.In the timeframe under scrutiny,a relatively modest subset of projects embraced eco-innovations and practices aligned with the circular economy.Our findings culminate in the formulation of practical implications to inv

关键词： Environment Sustainability Eco-innovation Innovation EU projects Entrepreneurship

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Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

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Oncology Research 2024年第5期32卷 807-815页

作者： MARKO SKELIN BRUNA PERKOV-STIPIČIN SANJA VUŠKOVIĆ MARINAŠANDRK PLEHAČEK ANE BAŠIĆ DAVIDŠARČEVIĆ maja ILIĆ IVAN KREČAK Pharmacy Department General Hospital ofŠibenik-Knin CountyŠibenikCroatia2 Faculty of MedicineUniversity of RijekaRijekaCroatia3 Undergraduate Study in NursingUniversity of Applied SciencesŠibenikCroatia4 Department of OncologyUniversity Hospital Center ZagrebZagrebCroatia5 Pharmacies JoukhadarSveta NedeljaCroatia6 Pharmacies Prima PharmeZagrebCroatia7 Pharmacy DepartmentGeneral Hospital ZadarZadarCroatia8 Pharmacy DepartmentGeneral Hospital PulaPulaCroatia9 Department of Internal MedicineGeneral Hospital ofŠibenik-Knin CountyŠibenikCroatia

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)globally.However,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated.This study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer settings.Methods:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each CPG.We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types.Results:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR A.Overall,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous versions.The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current version.In the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)recommendations.Significant variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer types.Conclusion:One-third of the current ESMO CPG recommendations are supported by the highest level of evidence.More well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

关键词： ESMO guidelines Clinical practice guidelines Level of evidence Grade of recommendation

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机器人辅助心电信号监测及康复训练系统

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高技术通讯 2024年第5期34卷 535-544页

作者：卢振利朱健美单长考刘燕赵宇 Pencic Marko Cavic'maja Ilieva Roumiana Mernik Marjan 常熟理工学院商学院盐城224051 盐城工学院机械工程学院常熟215500 常熟理工学院电气与自动化工程学院常熟215500 诺维萨德大学技术科学学院塞尔维亚诺维萨德21000 索菲亚工业大学管理学院保加利亚索菲亚1000 马里博尔大学电气工程和计算机科学学院斯洛文尼亚马里博尔462000

在心电信号的基础上设计心脏康复训练系统,本文总结了机器人辅助心脏康复研究国内外现状,从心电监测、机器人辅助康复系统设计上进行阐述。在心电监测装置上实现上下位机通信,在机器人辅助系统设计中,通过使用Visual Studio、Coppeliasi... 详细信息

在心电信号的基础上设计心脏康复训练系统,本文总结了机器人辅助心脏康复研究国内外现状,从心电监测、机器人辅助康复系统设计上进行阐述。在心电监测装置上实现上下位机通信,在机器人辅助系统设计中,通过使用Visual Studio、Coppeliasim及Kinect设备三者进行通信,控制仿真机器人完成康复动作并严格识别、判定患者康复动作合格程度,以此来帮助心脏病患者进行康复动作训练。

关键词：心电监测人机交互心脏康复

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Semaglutide-eye-catching results

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World Journal of Diabetes 2023年第4期14卷 424-434页

作者： maja Cigrovski Berkovic Felice Strollo Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Endocrinology and Metabolism IRCCS San Raffaele PisanaRome 00163Italy

Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and,more recently,at higher doses,for the treatment of obesity.Both diseases are reaching epidemic proportions and often coexist,posing patients with a high risk for cardiovascular disease and death.Therefore,an agent such as semaglutide,which offers clinically significant weight loss and cardiovascular benefits,is essential and will be increasingly used in high-risk patients.However,during the SUSTAIN clinical trial program(Semaglutide Unabated Sustainability in treatment of type 2 diabetes),a safety issue concerning the progression and worsening of diabetic retinopathy emerged.The existing explanation so far mainly supports the role of the magnitude and speed of HbA1c reduction,a phenomenon also associated with insulin treatment and bariatric surgery.Whether and to which extent the effect is direct is still a matter of debate and an intriguing topic to investigate for suitable preventative and rehabilitative purposes.In this minireview,we will summarize the available data and suggest guidelines for a comprehensive semaglutide clinical utilization until new evidence becomes available.

关键词： Glucagon-like peptide-1 receptor agonists Semaglutide Diabetic retinopathy Microvascular complications Cardiovascular benefit Rehabilitation

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