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| 1 | Sympathetic nervous system activation and heart failure:Current state of evidence and the pathophysiology in the light of novel biomarkers显示文摘Heart failure(HF)is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target organs and tissues.The sympathetic nervous system(SNS)is upregulated in HF as evident in dysfunctional baroreceptor and chemoreceptor reflexes,circulating and neuronal catecholamine spillover,attenuated parasympathetic response,and augmented sympathetic outflow to the heart,kidneys and skeletal muscles.When these sympathoexcitatory effects on the cardiovascular system are sustained chronically they initiate the vicious circle of HF progression and become associated with cardiomyocyte apoptosis,maladaptive ventricular and vascular remodeling,arrhythmogenesis,and poor prognosis in patients with HF.These detrimental effects of SNS activity on outcomes in HF warrant adequate diagnostic and treatment modalities.Therefore,this review summarizes basic physiological concepts about the interaction of SNS with the cardiovascular system and highlights key pathophysiological mechanisms of SNS derangement in HF.Finally,special emphasis in this review is placed on the integrative and up-to-date overview of diagnostic modalities such as SNS imaging methods and novel laboratory biomarkers that could aid in the assessment of the degree of SNS activation and provide reliable prognostic information among patients with HF. | Josip Anđelo Borovac Domenico D'Amario Josko Bozic Duska Glavas | 2020 | World Journal of Cardiology2020，12，8： | 14 |
| 2 | Inactive matrix Gla protein is elevated in patients with inflammatory bowel disease显示文摘BACKGROUND Matrix Gla protein(MGP)is a vitamin K dependent peptide which has an established role in suppression of vascular calcification.Recent studies have pointed to a possible link between immunomodulatory effect of MGP and inflammatory bowel disease(IBD).AIM To compare plasma levels of dephosphorylated and uncarboxylated MGP(dpucMGP)between IBD patients and controls.METHODS This cross-sectional study was conducted on 70 patients with IBD(30 patients with ulcerative colitis and 40 patients with Crohn’s disease)and 60 age and gender matching healthy controls.Plasma dp-ucMGP levels were analyzed from blood samples by CLIA method using IDS-iSYS InaKtif MGP(Immunodiagnostic Systems,Frankfurt,Germany)according to the manufacturer's instructions.fecal calprotectin(FC)levels were determined from stool samples by turbidimetric immunoassay method using Bühlmann fecal calprotectin turbo assay(Bühlmann Laboratories Aktiengesellschaft,Schonenbuch,Switzerland).Other parameters were analyzed according to the standard laboratory procedures.RESULTS Plasma levels of dp-ucMGP were significantly higher in patients with IBD compared to the healthy control group(629.83±124.20 pmol/mL vs 546.7±122.09 pmol/mL,P<0.001),and there was no significant difference between patients with Crohn’s disease and patients with ulcerative colitis(640.02±131.88 pmol/mL vs 616.23±113.92 pmol/mL,P=0.432).Furthermore,a significant positive correlation of plasma dp-ucMGP levels was found with both FC levels(r=0.396,P<0.001)and high sensitivity C-reactive protein(hsCRP)levels(r=0.477,P<0.001).Moreover,in the total study population a significant positive correlation was found between dp-ucMGP with age(r=0.210,P=0.016)and waist circumference(r=0.264,P=0.002).Multiple linear regression analysis showed that dp-ucMGP levels retained significant association with FC(β±SE,0.06±0.02,P=0.003).CONCLUSION Study results support experimental data of MGP immunomodulatory IBD effect and indicate potential involvement in the pathophysiology of the disease,and possibly extraintestinal manifestations. | Darko Brnic Dinko Martinovic Piero Marin Zivkovic Daria Tokic Marino Vilovic Doris Rusic Ivana Tadin Hadjina Christian Libers Sandro Glumac Daniela Supe-Domic Ante Tonkic Josko Bozic | 2020 | World Journal of Gastroenterology2020，26，32： | 5 |
| 3 | Role of endoscopic ultrasound in anticancer therapy:Current evidence and future perspectives显示文摘The digestive system is one of the most common sites of malignancies in humans.Since gastrointestinal tumors represent a massive global health burden both in terms of morbidity and health care expenditures,scientists continuously develop novel diagnostic and therapeutic methods to ameliorate the detrimental effects of this group of diseases.Apart from the well-established role of the endoscopic ultrasound(EUS)in the diagnostic course of gastrointestinal and hepatobiliary malignancies,we have recently become acquainted with a vast array of its therapeutic possibilities.A multitude of previously established,evidence-based methods that might now be guided by the EUS emerged:Radiofrequency ablation,brachytherapy,fine needle injection,celiac plexus neurolysis,and endoscopic submucosal dissection.In this review we endeavored to provide a comprehensive overview of the role of these methods in different malignancies of the digestive system,primarily in the treatment and symptom control in pancreatic cancer,and additionally in the management of hepatic,gastrointestinal tumors,and pancreatic cysts. | Andre Bratanic Dorotea Bozic Antonio Mestrovic Dinko Martinovic Marko Kumric Tina Ticinovic Kurir Josko Bozic | 2021 | World Journal of Gastrointestinal Oncology2021，13，12： | 2 |
| 4 | Role of novel biomarkers in diabetic cardiomyopathy显示文摘Diabetic cardiomyopathy(DCM)is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension.As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate,various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM,with little success so far.Hence,we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM.Among the array of biomarkers we thoroughly analyzed,long noncoding ribonucleic acids,soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection,as their plasma/serum levels accurately correlate with the early stages of DCM.The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients.The purpose of the screening test would be to direct affected patients to more specific confirmation tests.This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach. | Marko Kumric Tina Ticinovic Kurir Josip A Borovac Josko Bozic | 2021 | World Journal of Diabetes2021，12，6： | 1 |
| 5 | Discontinuation of therapy in inflammatory bowel disease: Current views显示文摘The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease(IBD).The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission.In patients with achieved long-term remission,the question of de-escalation or discontinuation of therapy arises,considering the possible side effects and economic burden of long-term therapy.For each of the drugs used in IBD(5-aminosalycaltes,immunomodulators,biological drugs,small molecules)there is a risk of relapse.Furthermore,studies show that more than 50%of patients who discontinue therapy will relapse.Based on the findings of large studies and meta-analysis,relapse of disease can be expected in about half of the patients after therapy withdrawal,in case of monotherapy with aminosalicylates,immunomodulators or biological therapy.However,longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor.It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking.Before making a decision on discontinuation of therapy,it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse.Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse.Several other predictive factors have also been identified,such as:High Crohn's disease activity index or Harvey Bradshaw index,younger age(<40 years),longer disease duration(>40 years),smoking,young age of disease onset,steroid use 6-12 months before cessation.An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs.The decision to discontinue therapy must be based on individual approach,taking into account the severity,extension,and duration of the disease,the possibility of side adverse effects,the risk of relapse,and patient’s preferences. | Antonio Meštrović Marko Kumric Josko Bozic | 2024 | World Journal of Clinical Cases2024，12，10： | 0 |
| 6 | Urotensin II levels in patients with inflammatory bowel disease显示文摘BACKGROUND Patients with inflammatory bowel disease(IBD)are associated with increased cardiovascular risk and have increased overall cardiovascular burden.On the other hand,urotensin II(UII)is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well.Furthermore,patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls.Since the features of IBD includes chronic inflammation and endothelial dysfunction as well,it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIM To determine serum UII levels in patients with IBD and to compare them to control subjects,as well as investigate possible associations with relevant clinical and biochemical parameters.METHODS This cross sectional study consecutively enrolled 50 adult IBD patients(26 with Crohn’s disease and 24 with ulcerative colitis)and 50 age and gender matched controls.Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines.Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation.Serum levels of UII were determined using the enzyme immunoassay kit for human UII,according to the manufacturer’s instructions.RESULTS IBD patients have significantly higher concentrations of UII when compared to control subjects(7.57±1.41 vs 1.98±0.69 ng/mL,P<0.001),while there were no significant differences between Crohn’s disease and ulcerative colitis patients(7.49±1.42 vs 7.65±1.41 ng/mL,P=0.689).There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels(r=0.491,P<0.001)and a significant negative correlation between serum UII levels and total proteins(r=-0.306,P=0.032).Additionally,there was a significant positive correlation between serum UII levels with both systolic(r=0.387,P=0.005)and diastolic(r=0.352,P=0.012)blood pressure.Moreover,serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity(r=0.425,P=0.048)and Simple Endoscopic Score for Crohn’s Disease(r=0.466,P=0.028)scores.Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide(β±standard error,0.262±0.076,P<0.001)and systolic blood pressure(0.040±0.017,P=0.030).CONCLUSION It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients,and its purpose should be investigated in further studies. | Damir Alicic Dinko Martinovic Doris Rusic Piero Marin Zivkovic Ivana Tadin Hadjina Marino Vilovic Marko Kumric Daria Tokic Daniela Supe-Domic Slaven Lupi-Ferandin Josko Bozic | 2021 | World Journal of Gastroenterology2021，27，36： | 0 |
| 7 | Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease显示文摘BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-15 serum levels were higher in patients with anemia(1256(502-2100)pg/mL vs 444(412-795)pg/mL,P<0.001).CONCLUSION For the first time,we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls,and the results imply that GDF-15 might be involved in IBD pathophysiology.Yet,it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients. | Ante Tonkic Marko Kumric Ivna Akrapovic Olic Doris Rusic Piero Marin Zivkovic Daniela Supe Domic Zeljko Sundov Ivan Males Josko Bozic | 2024 | World Journal of Gastroenterology2024，30，13： | 0 |
| 8 | Impact of the COVID-19 pandemic on inflammatory bowel disease patients:A review of the current evidence显示文摘Since the initial coronavirus disease 2019(COVID-19)outbreak in China in December 2019,the infection has now become the biggest medical issue of modern medicine.Two major contributors that amplified the impact of the disease and subsequently increased the burden on health care systems were high mortality among patients with multiple co-morbidities and overcapacity of intensive care units.Within the gastroenterology-related community,particular concern was raised with respect to patients with inflammatory bowel disease(IBD),as those patients are prone to opportunistic infections mainly owing to their immunosuppressive-based therapies.Hence,we sought to summarize current knowledge regarding COVID-19 infection in patients with IBD.Overall,it seems that IBD is not a comorbidity that poses an increased risk for COVID-19 acquisition,except in patients treated with 5-aminosalicylates.Furthermore,outcomes of the infected patients are largely dependent on therapeutic modality by which they are treated,as some worsen the clinical course of COVID-19 infection,whereas others seem to dampen the detrimental effects of COVID-19.Finally,we discussed the present and the future impact of COVID-19 pandemic and concomitantly increased health care burden on IBD-management. | Marko Kumric Tina Ticinovic Kurir Dinko Martinovic Piero Marin Zivkovic Josko Bozic | 2021 | World Journal of Gastroenterology2021，27，25： | 0 |
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