Медицински факултет [Научни радови] / Faculty of Medicine [Scientific papers]

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    Adrenal Abscesses: A Systematic Review of the Literature
    (MDPI, 2023) Gligorijevic, Nikola; Kaljevic, Marija; Radovanovic, Natasa; Jovanovic, Filip; Joksimovic, Bojan; Singh, Sandra; Dumic, Igor
    Objective: To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Design: Systematic literature review. Methods: We performed a search in the PubMed database using search terms: ‘abscess and adrenal glands’, ‘adrenalitis’, ‘infection and adrenal gland’, ‘adrenal abscess’, ‘adrenal infection’ and ‘infectious adrenalitis’. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Results: Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with Histoplasma capsulatum (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia (p = 0.048). Conclusion: Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, Histoplasma capsulatum is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.
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    Antiphospholipid Antibodies and Vascular Thrombosis in Patients with Severe Forms of COVID-19
    (MDPI, 2023) Zlatković-Švenda, Mirjana; Ovuka, Milica; Ogrič, Manca; Čučnik, Saša; Žigon, Polona; Radivčev, Aleksandar; Zdravković, Marija; Radunović, Goran
    Antiphospholipid antibodies (aPLA) are a laboratory criterion for the classification of antiphospholipid syndrome (APS) and are known to cause clinical symptoms such as vascular thrombosis or obstetric complications. It is suggested that aPLA may be associated with thromboembolism in severe COVID-19 cases. Therefore, we aimed to combine clinical data with laboratory findings of aPLA at four time points (admission, worsening, discharge, and 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. In 111 patients with COVID-19 pneumonia, current and past history of thrombosis and pregnancy complications were recorded. Nine types of aPLA were determined at four time points: anticardiolipin (aCL), anti- 2-glycoprotein I (anti- 2GPI), and antiphosphatidylserine/ prothrombin (aPS/PT) of the IgM, IgG, or IgA isotypes. During hospitalization, seven patients died, three of them due to pulmonary artery thromboembolism (none were aPLA positive). Only one of the five who developed pulmonary artery thrombosis was aPLA positive. Out of 9/101 patients with a history of thrombosis, five had arterial thrombosis and none were aPLA positive at admission and follow-up; four had venous thrombosis, and one was aPLA positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPLA positive at discharge only, compared to 26.1% without a history of thrombosis (p = 0.041). Patients with severe forms of COVID-19 and positive aPLA should receive the same dose and anticoagulant medication regimen as those with negative aPLA because those antibodies are mostly transiently positive and not linked to thrombosis and fatal outcomes.
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    Breaking the Gingival Barrier in Periodontitis
    (MDPI, 2023) Vitkov, Ljubomir; Singh, Jeeshan; Schauer, Christine; Minnich, Bernd; Krunić, Jelena; Oberthaler, Hannah; Gamsjaeger, Sonja; Herrmann, Martin; Knopf, Jasmin; Hannig, Matthias
    The break of the epithelial barrier of gingiva has been a subject of minor interest, albeit playing a key role in periodontal pathology, transitory bacteraemia, and subsequent systemic lowgrade inflammation (LGI). The significance of mechanically induced bacterial translocation in gingiva (e.g., via mastication and teeth brushing) has been disregarded despite the accumulated knowledge of mechanical force effects on tight junctions (TJs) and subsequent pathology in other epithelial tissues. Transitory bacteraemia is observed as a rule in gingival inflammation, but is rarely observed in clinically healthy gingiva. This implies that TJs of inflamed gingiva deteriorate, e.g., via a surplus of lipopolysaccharide (LPS), bacterial proteases, toxins, Oncostatin M (OSM), and neutrophil proteases. The inflammation-deteriorated gingival TJs rupture when exposed to physiological mechanical forces. This rupture is characterised by bacteraemia during and briefly after mastication and teeth brushing, i.e., it appears to be a dynamic process of short duration, endowed with quick repair mechanisms. In this review, we consider the bacterial, immune, and mechanical factors responsible for the increased permeability and break of the epithelial barrier of inflamed gingiva and the subsequent translocation of both viable bacteria and bacterial LPS during physiological mechanical forces, such as mastication and teeth brushing.
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    Dysfunctions of Neutrophils in the Peripheral Blood of Children with Cystic Fibrosis
    (MDPI, 2023) Bakalović, Ganimeta; Bokonjić, Dejan; Mihajlović, Dušan; Čolić, Miodrag; Mališ, Vanja; Drakul, Marija; Tomić, Sergej; Jojić, Ivan; Rakočević, Sara; Popović, Darinka; Kozić, Ljiljana; Vasiljević, Miloš; Bekić, Marina; Mašić, Srđan; Ljuboja, Olivera
    Dysfunction of neutrophils in patients with cystic fibrosis (CF) is best characterized in bronchoalveolar lavage (BAL), whereas peripheral blood neutrophils are less examined, and the results are contradictory, especially in younger populations. Therefore, this work aimed to study functional and phenotypic changes in circulating neutrophils in children with CF. The study included 19 CF children (5–17 years) and 14 corresponding age-matched healthy children. Isolated neutrophils were cultured either alone or with different stimuli. Several functions were studied: apoptosis, NET-osis, phagocytosis, and production of reactive oxygen species (ROS), neutrophil elastase (NE), and 11 cytokines. In addition, the expression of 20 molecules involved in different functions of neutrophils was evaluated by using flow cytometry. CF neutrophils showed reduced apoptosis and lower production of NE and IL-18 compared to the healthy controls, whereas IL-8 was augmented. All of these functions were further potentiated after neutrophil stimulation, which included higher ROS production and the up-regulation of CD11b and IL-10 expression. NET-osis was higher only when neutrophils from moderate–severe CF were treated with Pseudomonas aeruginosa, and the process correlated with forced expiratory volume in the first second (FEV1). Phagocytosis was not significantly changed. In conclusion, circulating neutrophils from children with CF showed fewer impaired changes in phenotype than in function. Functional abnormalities, which were already present at the baseline levels in neutrophils, depended on the type of stimuli that mimicked different activation states of these cells at the site of infection.
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    Age-specific causes of upper gastrointestinal bleeding in children
    (Baishideng Publishing Group, 2023) Kocic, Marija; Rasic, Petar; Marusic, Vuk; Prokic, Dragan; Savic, Djordje; Milickovic, Maja; Kitic, Ivana; Mijovic, Tanja; Sarajlija, Adrijan
    The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While particular causes such as vitamin K deficiency and cow’s milk protein allergy are limited to specific age groups, occurring only in neonates and infants, others such as erosive esophagitis and gastritis may be identified at all ages. Furthermore, the incidence of UGIB is variable throughout the world and in different hospital settings. In North America and Europe, most UGIBs are nonvariceal, associated with erosive esophagitis, gastritis, and gastric and duodenal ulcers. In recent years, the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries. However, variceal bleeding still predominates in certain parts of the world, especially in South Asia. The most severe hemorrhage arises from variceal bleeding, peptic ulceration, and disseminated intravascular coagulation. Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients. Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings, the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIB includes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability, followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis in the pediatric population because some of them are unique to children. Endoscopic techniques are of significant diagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally, surgical treatment is reserved for the most severe bleeding.