Background and objectives: The COVID-19 pandemic has had an unprecedented reliance on informal caregivers as one of the pillars of healthcare systems. The aim of this study was to assess the quality of life of informal caregivers during the COVID-19 epidemic in Serbia. Materials and Methods: A cross-sectional study was conducted among informal caregivers during the COVID-19 epidemic in Serbia. Physical and mental quality of life was measured by the 36-Item Short-Form Health Survey. Additional data included sociodemographic characteristics, caregiver and care recipient characteristics, and COVID-19 related concerns. The qualitative component was performed using focus groups and individual in-depth interviews. Results: Out of 112 informal caregivers enrolled, most were female (80%), and the average age was 51.1 ± 12.3 years. The majority was delivering care to one person, who was a family member, on a daily basis (86.4%, 92%, and 91.1%, respectively). In multiple regression models, significant predictors of caregivers’ physical health were delivering care to a family member and a higher level of care complexity, while significant predictors of caregivers’ mental health were a higher level of care complexity and increased concerns about self-health and the health of the person being cared for due to the COVID-19 epidemic. Conclusions: Informal caregivers are experiencing negative physical and mental health outcomes during the COVID-19 epidemic in Serbia.

Introduction. Mortality among critically ill COVID-19 patients remains relatively high despite different potential therapeutic modalities being introduced recently. The treatment of critically ill patients is a challenging task, without identified credible predictors of mortality. Methods. We performed an analysis of 160 consecutive patients with confirmed COVID-19 infection admitted to the Respiratory Intensive Care Unit between June 23, 2020, and October 2, 2020, in University Hospital Center Bezanijska kosa, Belgrade, Serbia. Patients on invasive, noninvasive ventilation and high flow oxygen therapy with moderate to severe ARDS, according to the Berlin definition of ARDS, were selected for the study. Demographic data, past medical history, laboratory values, and CT severity score were analyzed to identify predictors of mortality. Univariate and multivariate logistic regression models were used to assess potential predictors of mortality in critically ill COVID-19 patients. Results. The mean patient age was 65.6 years (range, 29–92 years), predominantly men, 68.8%. 107 (66.9%) patients were on invasive mechanical ventilation, 31 (19.3%) on noninvasive, and 22 (13.8%) on high flow oxygen therapy machine. The median total number of ICU days was 10 (25th to 75th percentile: 6–18), while the median total number of hospital stay was 18 (25th to 75th percentile: 12–28). The mortality rate was 60% (96/160). Univariate logistic regression analysis confirmed the significance of age, CRP, and lymphocytes at admission to hospital, serum albumin, D-dimer, and IL-6 at admission to ICU, and CT score. Serum albumin, D-dimer, and IL-6 at admission to ICU were independently associated with mortality in the final multivariate analysis. Conclusion. In the present study of 160 consecutive critically ill COVID-19 patients with moderate to severe ARDS, IL-6, serum albumin, and D-dimer at admission to ICU, accompanied by chest CT severity score, were marked as independent predictors of mortality.

Citations are an important, but often overlooked, part of every scientific paper. They allow the reader to trace the flow of evidence, serving as a gateway to relevant literature. Most scientists are aware of citations errors, but few appreciate the prevalence of these problems. The purpose of this study was to examine how often frequently cited papers in biomedical scientific literature are cited inaccurately. The study included an active participation of first authors of included papers; to first-hand verify the citations accuracy. Findings from feasibility study, where we reviewed 1,540 articles containing 2,526 citations of 14 most cited articles in which the authors were affiliated with the Faculty of Medicine University of Belgrade, were further evaluated for external confirmation in an independent verification set of articles. Verification set included 4,912 citations identified in 2,995 articles that cited 13 most cited articles published by authors affiliated with the Mayo Clinic Division of Nephrology and Hypertension. A citation was defined as being accurate if the cited article supported or was in accordance with the statement by citing authors. At least one inaccurate citation was found in 11% and 15% of articles in the feasibility study and verification set, respectively, suggesting that inaccurate citations are common in biomedical literature. The most common problem was the citation of nonexistent findings (38.4%), followed by an incorrect interpretation of findings (15.4%). One fifth of inaccurate citations were due to chains of inaccurate citations. Based on these findings, several actions to reduce citation inaccuracies have been proposed.

Background Studies have recently examined the role of epigenetic mechanisms in preeclampsia pathophysiology. One commonly examined epigenetic process is DNA methylation. This heritable epigenetic marker is involved in many important cellular functions. The aim of this study was to establish the association between DNA methylation and preeclampsia and to critically appraise the roles of major study characteristics that can significantly impact the association between DNA methylation and preeclampsia. Main body A systematic review was performed by searching PubMed, Web of Science, and EMBASE for original research articles published over time, until May 31, 2019 in English. Eligible studies compared DNA methylation levels in pregnant women with vs. without preeclampsia. Ninety articles were included. Epigenome-wide studies identified hundreds of differentially methylated places/regions in preeclamptic patients. Hypomethylation was the predominant finding in studies analyzing placental tissue (14/19), while hypermethylation was detected in three studies that analyzed maternal white blood cells (3/3). In candidate gene studies, methylation alterations for a number of genes were found to be associated with preeclampsia. A greater number of differentially methylated genes was found when analyzing more severe preeclampsia (70/82), compared to studies analyzing less severe preeclampsia vs. controls (13/27). A high degree of heterogeneity existed among the studies in terms of methodological study characteristics including design (study design, definition of preeclampsia, control group, sample size, confounders), implementation (biological sample, DNA methylation method, purification of DNA extraction, and validation of methylation), analysis (analytical method, batch effect, genotyping, and gene expression), and data presentation (methylation quantification measure, measure of variability, reporting). Based on the results of this review, we provide recommendations for study design and analytical approach for further studies. Conclusions The findings from this review support the role of DNA methylation in the pathophysiology of preeclampsia. Establishing field-wide methodological and analytical standards may increase value and reduce waste, allowing researchers to gain additional insights into the role of DNA methylation in the pathophysiology of preeclampsia.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE.Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size.Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55–2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33–1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25–2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36–2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83–5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69–2.58), and significantly lower for miRNA-376c (SMD = –4.86, 95%CI = –9.51 to –0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35–3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = –0.47, 95%CI = –0.91 to –0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis.Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE.

Background: The objective of this study was to assess the complex relationship between the multiple determinants of the caregiving process, the caregiver burden, and depression during the COVID-19 pandemic in Serbia. Methods: A cross-sectional study was conducted on a nationally representative sample (n = 798) during the COVID-19 pandemic in Serbia from March to September 2020. A nine-section questionnaire designed for this study included the characteristics of caregivers, characteristics of care and care recipients, COVID-19 related questions, and the following standardized instruments: 12-Item Short-Form Health Survey, Fatigue Severity Scale, Activities of Daily Living Scale and Instrumental Activities of Daily Living Scale, Zarit Caregiver Burden Scale, and Beck Depression Inventory. Path analysis was used for the simultaneous assessment of the direct and indirect relationships of all determinants. Results: More than two thirds (71.9%) of informal caregivers experienced a burden, and more than one quarter (27.1%) had depression symptomatology. Self-rated physical health, need for psychosocial support, and caregiver burden were the main direct predictors of depression. Multiple determinants of the caregiving process had indirect effects on depressive symptomatology via the caregiver burden as a mediating factor. Conclusions: The subjective burden presented a significant risk factor for depressive symptoms in caregivers during the COVID-19 pandemic. The provision of psychosocial support was identified as an important opportunity to reduce depressive risk in informal caregivers.

Introduction: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. Material and Methods: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients’ survival. The studies published before 22 October 2020 were identified through the PubMED, EMBASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. Results: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI: 1.95–2.99 and HR = 2.46, 95% CI: 2.01–3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90–3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02–27.63). Conclusion: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients.

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