Milica Stojković Lalošević

University of Belgrade

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Tamara Alempijević

University of Belgrade

Sanja Dragašević

University of Belgrade

Igor Dumic

Mayo Clinic

A Marković

University of Belgrade

Mirjana Stojković

Univerzitetski Klinički Centar Srbije

Dušan Popović

University of Belgrade

MŠ

Miloš Štulić

University of Belgrade

Mihailo Stjepanović

University of Belgrade

Tomica Milosavljević

Euromedik

Marija Stojanović

University of Belgrade

Cooperative Institutions

University of Belgrade

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Centar za Promociju Nauke

Univerzitetski Klinički Centar Srbije

Center for Health, Exercise and Sport Sciences

Institut za Reumatologiju

University of Belgrade – Faculty of Medicine

University Hospital Center Dr Dragiša Mišović

Faculty (United Kingdom)

University of Kragujevac

University of Nis

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Doppler assessment of splanchnic arterial flow in patients with liver cirrhosis: Correlation with nitric oxide

Medicinska istrazivanja (2023)

Tijana Glišić Dušan Popović Milica Stojković Lalošević Jelena Martinov Marija Stojanović

Introduction/aim: Nitric oxide (NO) is a key mediator which, paradoxically, regulates sinusoidal (intrahepatic) and systemic/splanchnic circulation. The main goal of this study was to measure NO and compare serum values of NO with flow data in visceral blood vessels of the liver, spleen, kidney and intestine in patients with cirrhosis. Material and methods: This prospective study included 80 patients with cirrhosis of the liver. Doppler ultrasonography was used to assess flow velocity and resistive index (RI) in the hepatic (HA), right (RRA), and left renal (LRA), splenic (SA) and superior mesenteric artery (SMA). NO concentration was determined using the DetectX® Nitric Oxide colorimetric detection kit. Results: We found a statistically significant difference in the mean NO value in the group of patients without ascites compared to the ascites group, as well as in the group of patients with A stage in relation to C stage of cirrhosis (p <0.05). There is statistically significant negative correlation between NO and diameter, and maximal and minimal velocity in LRA. There is significant positive correlation between NO and minimal velocity in SMA. Conclusions: In this study, we found that patients with cirrhosis of the liver were exposed to significantly higher RI LRA, RRA, SA and HA. In patients with cirrhosis complicated by ascites and in those with end stage liver disease, the NO level was significantly higher. The concentration of NO had an effect on the diameter and flow rate in the LRA and flow rate in SMA.

Liver disease

10.5937/medi55-41696

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Gastrointestinal Tract Disorders in Older Age

Canadian Journal of Gastroenterology and Hepatology (2019)

Igor Dumic Terri Nordin Mladen Jecmenica Milica Stojković Lalošević Tomica Milosavljević

Considering an increase in the life expectancy leading to a rise in the elderly population, it is important to recognize the changes that occur along the process of aging. Gastrointestinal (GI) changes in the elderly are common, and despite some GI disorders being more prevalent in the elderly, there is no GI disease that is limited to this age group. While some changes associated with aging GI system are physiologic, others are pathological and particularly more prevalent among those above age 65 years. This article reviews the most important GI disorders in the elderly that clinicians encounter on a daily basis. We highlight age-related changes of the oral cavity, esophagus, stomach, small and large bowels, and the clinical implications of these changes. We review epidemiology and pathophysiology of common diseases, especially as they relate to clinical manifestation in elderly. Details regarding management of specific disease are discussed in detail if they significantly differ from the management for younger groups or if they are associated with significant challenges due to side effects or polypharmacy. Cancers of GI tract are not included in the scope of this article.

10.1155/2019/6757524

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EncephalApp Stroop Test as a Screening Tool for the Detection of Minimal Hepatic Encephalopathy in Patients with Cirrhosis—Single-Center Experience

Gastroenterology Insights (2024)

Marko Vojnović Ivana Pantić Goran Janković Miloš Štulić Milica Stojković Lalošević

Background: Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy. One of the neuropsychological tests that detects MHE is the Stroop test (via EncephalApp). The aim was to evaluate the Stroop test for the screening and diagnosis of MHE. Methods: This prospective case–control study was performed at the Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, and included patients with cirrhosis and MHE and healthy controls. In all patients, the presence of MHE was confirmed using the animal naming test. The Stroop test was performed on each participant, and the results were compared between the two groups. The test has two components, the “OFF” and “ON” states. Results: A total of 111 participants were included. The median OFF time did not differ between the two groups, 106.3 and 91.4, p > 0.05. However, in patients with MHE, the median values of ON time and total time were significantly higher, with 122.3 vs. 105.3 and 228.0 vs. 195.6, respectively, p < 0.05. Statistical significance between patients and controls in examined parameters was detected in younger participants and the group with higher educational levels. Conclusions: The Stroop test displayed limited sensitivity in Serbian patients. Age and education affect time measurements and test performance.

Hepatic Encephalopathy

Single Center

Stroop effect

Center (category theory)

10.3390/gastroent15010017

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The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis

Medicina (2018)

Miloš Štulić Djordje Culafic Radmila Obrenović Goran Janković Tamara Alempijević

Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis.

Resistive index

Clinical Significance

Liver disease

Hepatic fibrosis

10.3390/medicina54030037

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Evaluating ground glass opacities (GGO) in the COVID-19 era. Do autoantibodies help?

The Journal of Infection in Developing Countries (2022)

Nina Pejic Milica Stojković Lalošević Miloš Štulić Milica Ćulafić Djordje Culafic

Introduction: COVID-19 is an infectious disease, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and there have been outbreaks worldwide. The presentation may include unspecific and mild symptoms, myalgia, headaches, high fever, dry cough, severe dyspnea and acute respiratory distress syndrome (ARDS). Case study: We present a rare case of microscopic polyangiitis (MPA) with interstitial lung disease and without renal involvement misdiagnosed as COVID-19. Conclusions: Differential diagnosis of COVID-19 is extremely important, and must be correctly identified in order to proceed with correct treatment.

myalgia

10.3855/jidc.16401

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Evaluation of treatment outcome in patients with acute-on-chronic liver failure using clinical scores

Srpski arhiv za celokupno lekarstvo (2019)

Tamara Alempijević Milica Stojković Lalošević Sanja Dragašević Nevena Jocic Marko Baralić

Introduction/Objective. Due to a very high mortality risk, acute-on-chronic liver failure (ACLF) patients require early identification and intensive treatment. Precise prediction is crucial for determining the urgency degree and therapy appropriateness, considering high mortality and multitude of clinical resources. The aim of our study was to determine the exact cut-off values of various prognostic scores in the prediction of morality of ACLF. Methods. This prospective study includes chronic liver disease (CLD) patients, admitted due to decompensation, that were subsequently diagnosed with ACLF at the Emergency unit. All patients were evaluated based on various prognostic scores, including Child?Pugh, MELD Na, MELD, SOFA, APACHE II, and CLIF C, which were calculated on admission. Results. Alcoholic liver disease (ALD) was the most common underlying CLD cause (77.9%), followed by viral (8.6%), autoimmune (7.7%), and other causes (5.8%). A total of 37.5% of the patients died at the end of the first month of treatment. Average values of Child?Pugh, MELD Na, MELD, SOFA, APACHE II, and CLIF C scores were significantly higher in patients who died compared to survivors (p < 0.05). CLIF C score showed the best performance with a cut-off value of 50.5, with a sensitivity of 94.9% and specificity of 40%. Conclusion. ACLF remains a condition with a high short-term mortality. Of all of the scores examined in our study, CLIF C proved to be the best scoring system for predicting short term and end of treatment mortality in patients with ACLF.

Decompensation

Chronic liver disease

Liver disease

10.2298/sarh190511093m

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PB2037: NEW TERT VARIANT IN A FAMILY WITH APLASTIC ANEMIA

HemaSphere (2023)

Marijana Virijević Irena Marjanović Marina Andjelković Nada Suvajdžić Ljubomir Jaković

Topic: 11. Bone marrow failure syndromes incl. PNH - Biology & Translational Research Background:TERT gene, the most frequently mutated gene in patients with telomere biology disorders (telomeropathies), encode telomerase reverse transcriptase enzyme. Heterozygous variants in the TERT gene impair telomerase activity by haploinsufficiency and pathogenic variants are associated with bone marrow failure syndrome and acute myeloid leukemia predisposition. TERT variants show incomplete penetrance and can also be found in asymptomatic family members. Some patients with telomeropathies present with severe symptoms at early age, and in other diseases may appear later in life like aplastic anemia, pulmonary or hepatic fibrosis. Affected families may show anticipation that may result in more severe forms of the disease in succeeding generations. Due to the rarity of the disease and the small number of clinical trials, telomeropathies are often unrecognized and misdiagnosed. Aims: To report a novel variant in TERT gene in familial hematopoietic disorder. Methods: Next Generation Sequencing of DNA isolated from peripheral blood of a patient (older sister) with clinical diagnosis of aplastic anemia, using TruSight One MiSeq platform (Illumina®) and segregation sequencing analysis of patient’s mother and younger sister. Results: We analyzed all three family members presented with a similar clinical appearance and hematology findings (moderate megaloblastic pancytopenia). Mother was diagnosed at age 14, but reevaluated before delivery in 2001 as hypoplastic MDS and trisomy 8 in karyotype with marked thrombocytopenia, being stable for years. Two daughters, both diagnosed as familiar aplastic anemia with normal karyotype, without elements of Fanconi anemia, at age of 13 and 14 yrs, also with profound thrombocytopenia without severe bleeding episodes. Moreover, lung and liver fibrosis were excluded. We identified a novel missense heterozygous variant c.2605G>A p.(Asp869Asn) in TERT gene in all three family members. This variant results in replacement of aspartic amino acid on 869 position in TERT enzyme polypeptide chain by asparagine. According to ACMG classification, detected variant is characterized as likely pathogenic, class 2. This variant is very rare and was detected in gnomAD exomes and gnomAD genomes data bases. It is located in highly conserved protein region and is very likely to disrupt the function of the enzyme. Summary/Conclusion: As patients with telomeropathies often have a history of macrocytosis and mild to moderate thrombocytopenia, that can be wrongly diagnosed as immune-mediated thrombocytopenia, myelodysplastic syndrome or moderate aplastic anemia, our findings indicate that TERT rare variants pass under-recognized in these patients. Therefore, this report emphasizes the importance for routine deep genetics screening for TERT rare variants in patients with family history of cytopenia, different bone marrow failure syndromes and aplastic anemia, regardless the age or clinical presentation. This investigation is able to identify clinically inapparent telomere biology disorder and improve outcomes through forehand diagnosis setting, genetic counseling and the precise therapy considerations especially stem cell grafting. E-Mail Address: [email protected] Keywords: Aplastic anemia, Telomere, Familial

Aplastic anemia

Haploinsufficiency

Bone marrow failure

Dyskeratosis congenita

10.1097/01.hs9.0000974956.62401.c5

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Not so innocent bystander - gallbladder varices without portal vein thrombosis

Srpski arhiv za celokupno lekarstvo (2020)

Tamara Alempijević Igor Dumic Ivana Ilic Marko Baralić Sanja Dragašević

Introduction. Gallbladder varices (GBV) represent a rare form of ectopic varices that usually occur in patients with portal hypertension and portal vein thrombosis. Case outline. We present a case of a 38-year-old woman with decompensated autoimmune liver cirrhosis who was referred to our institution for evaluation for liver transplantation. She was incidentally discovered to have GBV during a routine B-mode abdominal ultrasonography as part of pre-transplant evaluation. GBV were confirmed by the Color Doppler Sonography, and multi detector computed tomography angiography. Interestingly, portal vein was patent and without thrombus. Conclusion. Despite being asymptomatic in most cases, the presence of GBV is valuable information for a surgeon because they might be a source of potentially catastrophic bleeding, which is particularly poorly tolerated by patients with decompensated liver cirrhosis. Ultrasound has the irreplaceable role not only in discovering GBV, but in prompt diagnosis of rare, but unpredictable and fatal complications as well.

Portal vein thrombosis

10.2298/sarh200428050m

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Assessment of Duodenal Adenomas and Strategies for Curative Therapy

Digestive Diseases (2019)

Aleksandra Pavlović-Marković Sanja Dragašević Miodrag Krstić Milica Stojković Lalošević Tomica Milosavljević

The increasing incidence of duodenal neoplasm has underlined different methods of resection depending on the clinical presentation, endoscopic features and histopathology. In this comprehensive review, we systematically describe the current knowledge concerning the diagnosis and management of duodenal adenomas (DAs) and discuss data considering all possible therapeutic approaches.Among a variety of duodenal lesions, including neuroendocrine tumors and gastrointestinal stromal tumors, DAs present precancerous lesions of the duodenal papilla or non-ampullary region necessitating removal. DAs can occur sporadically (SDA) as rare lesions or relatively common in polyposis syndromes. The endoscopic resections of DA are associated with an increased degree of complexity due to distinctive anatomical properties of the duodenal wall, luminal diameter and the presence of ampulla with pancreatic and biliary drainage. The endoscopic techniques including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), and argon plasma coagulation ablation are suggested to be less invasive than surgical treatment, associated with shorter hospital stay and lower cost. According to the current clinical practice, surgery has been accepted as standard therapeutic approach in familial adenomatous polyposis patients with severe polyposis or DA not amenable to endoscopic resection. Key Messages: The strategy for endoscopic resection of DAs depends on the lesion size, morphology, location, and histopathology findings. Small adenomas are most frequently diagnosed and removed by standard CSP techniques, while large laterally spreading lesions and ampullary adenoma are referred for EMR or endoscopic papillectomy respectively. Screening colonoscopy is indicated in patients with SDA. Additional studies for new endoscopic strategies and techniques for curative therapy of DAs are needed to refine future management decisions. Complete resection of DA is considered curative, but nevertheless, long-term endoscopic follow-up is still required to detect and treat any recurrent arising lesions.

Major duodenal papilla

Endoscopic mucosal resection

Ampulla of Vater

Polypectomy

Tubular adenoma

Duodenoscopy

Histopathology

10.1159/000496697

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Endoscopic retrograde cholangiopancreatography training conditions, results from a pan‐European survey: Between vision and reality

United European Gastroenterology Journal (2024)

Karim Hamesch Oscar Cahyadi Stavros Dimitriadis Marcus Hollenbach Pilar Acedo

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) still has a relatively high complication rate, underscoring the importance of high‐quality training. Despite existing guidelines, real‐world data on training conditions remain limited. This pan‐European survey aims to systematically explore the perceptions surrounding ERCP training. Methods A survey was distributed through the friends of United European Gastroenterology (UEG) Young Talent Group network to physicians working in a UEG member or associated states who regularly performed ERCPs. Results Of 1035 respondents from 35 countries, 649 were eligible for analysis: 228 trainees, 225 trainers, and 196 individuals who regularly performed ERCP but were neither trainees nor trainers. The mean age was 43 years, with 72.1% identifying as male, 27.6% as female, and 0.3% as non‐binary. The majority (80.1%) agreed that a structured training regimen is desirable. However, only 13.7% of trainees and 28.4% of trainers reported having such a structured program in their institutions. Most respondents (79.7%) supported the concept of concentrating training in centers meeting specific quality metrics, with 64.1% suggesting a threshold of 200 annual ERCPs as a prerequisite. This threshold revealed that 36.4% of trainees pursued training in lower‐volume centers performing <200 ERCPs annually. As many as 70.1% of trainees performed <50 annual ERCPs, whereas only 5.0% of trainers performed <50 ERCPs annually. A low individual trainee caseload (<50 ERCPs annually) was more common in lower‐volume centers than in higher‐volume centers (82.9% vs. 63.4%). Conclusions The first pan‐European survey investigating ERCP training conditions reveals strong support for structured training and the concentration of training efforts within centers meeting specific quality metrics. Furthermore, this survey exposes the low availability of structured training programs with many trainees practicing at lower‐volume centers and 71% of all trainees having little hands‐on exposure. These data should motivate to standardize ERCP training conditions further and ultimately improve patient care throughout Europe.

Private practice

10.1002/ueg2.12684

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