Milin‐Lazović, Jelena

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.

Abstract 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 the present study was to examine how often frequently cited papers in biomedical scientific literature are cited inaccurately. The study included an active participation of the first authors of included papers; to first-hand verify the citations accuracy. Findings from feasibility study, where we reviewed 1540 articles containing 2526 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 4912 citations identified in 2995 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.

Reports highlighting the problems with the standard practice of using bar graphs to show continuous data have prompted many journals to adopt new visualization policies. These policies encourage authors to avoid bar graphs and use graphics that show the data distribution; however, they provide little guidance on how to effectively display data. We conducted a systematic review of studies published in top peripheral vascular disease journals to determine what types of figures are used, and to assess the prevalence of suboptimal data visualization practices. Among papers with data figures, 47.7% of papers used bar graphs to present continuous data. This primer provides a detailed overview of strategies for addressing this issue by (1) outlining strategies for selecting the correct type of figure depending on the study design, sample size, and the type of variable; (2) examining techniques for making effective dot plots, box plots, and violin plots; and (3) illustrating how to avoid sending mixed messages by aligning the figure structure with the study design and statistical analysis. We also present solutions to other common problems identified in the systematic review. Resources include a list of free tools and templates that authors can use to create more informative figures and an online simulator that illustrates why summary statistics are meaningful only when there are enough data to summarize. Last, we consider steps that investigators can take to improve figures in the scientific literature.

Objective To examine the effects of bowel management on urinary incontinence in patients with spina bifida associated with overactive bladder ( OAB ) and detrusor sphincter dyssynergia ( DSD ). Materials and Methods The research was carried out during the period 2014–2017. A total of 35 patients (group 1) were administered bowel management combined with anticholinergic medication therapy and clean intermittent catheterization ( CIC ) and 35 patients (group 2) were treated only with anticholinergic medication therapy and CIC . Bowel management included daily enema, laxative application and a special diet, with the aim of treating constipation, evaluated according to the Roma III criteria and echosonographically determined transversal rectal diameter. The effects of the administered bowel management on urinary incontinence were assessed according to the mean dry interval between two CIC s for all patients. All patients were followed up for 1 year, during which data were prospectively collected. Results There was no statistically significant difference with regard to age, gender and baseline clinical features between the two groups. In group 1, the mean ± sd dry interval between two CIC s was 150.0 ± 36.4 min, and group 2 it was 101.3 ± 51.6 min. There was a significant difference in urinary incontinence, i.e. in the mean dry interval, between the two groups ( P < 0.001). Conclusion Administering bowel management considerably increased the mean dry interval, thus greatly alleviating the symptoms of urinary incontinence. For this reason, bowel management should form an integral part of the treatment of patients with spina bifida and OAB and DSD .

ABSTRACTObjectivesPre‐eclampsia (PE) is a pregnancy‐specific hypertensive disorder that has been associated with cardiovascular risk factors and vascular changes, such as acute atherosis in placental blood vessels, similar to early‐stage atherosclerosis. The objective of this study was to determine whether women with PE have increased atherosclerotic burden, as determined by the carotid intima–media thickness (CIMT), compared with women without PE.MethodsWe conducted a systematic review and meta‐analysis of studies that reported CIMT, a non‐invasive, ultrasound‐based measure of subclinical atherosclerosis, in women who did vs those who did not have PE. Studies were eligible if they had been conducted during pregnancy or during the first decade postpartum, and if CIMT was measured in the common carotid artery. Studies published before 7 March 2016 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. Heterogeneity was assessed using the I2 statistic. Standardized mean difference (SMD) was used as a measure of effect size.ResultsFourteen studies were included in the meta‐analysis. Seven studies were carried out during pregnancy complicated by PE, 10 were carried out up to 10 years postpartum and three included measurements obtained at both time periods. Women who had PE had significantly higher CIMT than did those who did not have PE, both at the time of diagnosis (SMD, 1.10 (95% CI, 0.73–1.48); P < 0.001) and in the first decade postpartum (SMD, 0.58 (95% CI, 0.36–0.79); P < 0.001).ConclusionsAtherosclerotic load is present at the time of PE and may be a mechanism associated with the disease. Measurement of CIMT may offer an opportunity for the early identification of premenopausal women with atherosclerotic burden after a PE pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.RESUMENObjetivosLa preeclampsia (PE) es un trastorno hipertensivo específico del embarazo que ha sido asociada con factores de riesgo cardiovascular y cambios vasculares, tales como aterosis aguda en los vasos sanguíneos de la placenta, similares a las primeras etapas de la aterosclerosis. El objetivo de este estudio fue determinar si las mujeres con PE han aumentado la carga aterosclerótica, según lo determinado por el espesor del complejo íntima‐media de la arteria carótida (CIMT, por sus siglas en inglés), en comparación con las mujeres sin PE.MétodosSe realizó una revisión sistemática y un metaanálisis de estudios que reportaron el CIMT, una medida no invasiva de la aterosclerosis subclínica obtenida mediante ecografía, comparando mujeres con PE y mujeres sin ella. Solo se incluyeron estudios llevados a cabo durante el embarazo o durante la primera década después del parto, y en los que se midió el CIMT en la arteria carótida común. Se usaron las bases de datos de PubMed, EMBASE y Web of Science para identificar estudios publicados antes del 7 marzo de 2016. Dos revisores utilizaron formularios y protocolos preestablecidos para evaluar de forma independiente la elegibilidad de los estudios, a partir de los títulos y los resúmenes, y para realizar un cribado del texto completo, un resumen de los datos y una evaluación de calidad. La heterogeneidad se evaluó mediante el test estadístico I2. Se usó la diferencia de medias estandarizada (SMD, por sus siglas en inglés) como una medida de la magnitud del efecto.ResultadosEn el metaanálisis se incluyeron catorce estudios. Siete de los estudios se llevaron a cabo durante embarazos complicados por PE, 10 se realizaron hasta 10 años después del parto y tres incluyeron mediciones tomadas en ambos períodos. Las mujeres con PE tuvieron un CIMT significativamente mayor que aquellas que no la tenían, tanto en el momento del diagnóstico (SMD 1,10 (I 95%, 0,73‐1,48), P <0,001) como en la primera década después del parto (SMD 0,58 (IC 95%, 0,36‐0,79), P <0,001).ConclusionesLa carga aterosclerótica está presente en el momento de la PE y podría ser un mecanismo asociado con esta enfermedad. La medición del CIMT puede ofrecer una oportunidad para la identificación temprana de mujeres premenopáusicas con carga aterosclerótica después de un embarazo con PE.目的子痫前期(pre‐eclampsia,PE)是一种妊娠期特发的高血压疾病,与心血管危险因素和血管改变有关,如胎盘血管急性动脉粥样硬化,与早期动脉粥样硬化相似。本研究的目的是通过检测颈动脉内—中膜厚度(carotid intima–media thickness,CIMT),确定妊娠合并PE与无合并PE患者相比,动脉粥样硬化负担是否增加。方法我们对报道PE患者与无PE患者相比CIMT的研究进行系统综述和meta分析,CIMT为无创性、基于超声的亚临床动脉粥样硬化检测方法。纳入标准为:研究在妊娠期间或产后头10年进行并检测颈总动脉的CIMT。检索PubMed、EMBASE和Web of Science中发表的研究,时间截止至2016年3月7日。由两名人员根据预定的格式和方案,通过题目和摘要独立评估符合纳入标准的研究,并进行全文筛查、数据提取和质量评估。采用I2检验评估异质性。采用标准化均数差(SMD)检测效应量。结果meta分析中纳入14项研究。7项研究在妊娠合并PE时进行,10项研究在产后10年进行,3项研究在两个时间段均进行了检测。PE患者与无合并PE患者相比,确诊时[SMD,1.10(95% CI,0.73~1.48);P<0.001]以及产后头10年[SMD,0.58(95% CI,0.36~0.79);P<0.001] CIMT均明显较高。结论PE时存在动脉粥样硬化负担,它可能与疾病发病机制有关。通过检测CIMT,可以早期识别PE妊娠后存在动脉粥样硬化负担的绝经前女性。

Endothelial dysfunction is believed to play a critical role in preeclampsia; however, it is unclear whether this dysfunction precedes the pregnancy or is caused by pathophysiological events in early pregnancy. It is also unclear for how long vascular dysfunction may persist postpartum and whether it represents a mechanism linking preeclampsia with future cardiovascular disease. Our objective was to determine whether women with preeclampsia had worse vascular function compared with women who did not have preeclampsia by performing a systematic review and meta-analysis of studies that examined endothelial dysfunction using flow-mediated dilation. We included studies published before May 29, 2015, that examined flow-mediated dilation before, during, or after preeclampsia. Differences in flow-mediated dilation between study groups were evaluated by standardized mean differences. Out of 610 abstracts identified through PubMED, EMBASE, and Web of Science, 37 studies were eligible for the meta-analysis. When compared with women who did not have preeclampsia, women who had preeclampsia had lower flow-mediated dilation before the development of preeclampsia (≈20–29 weeks gestation), at the time of preeclampsia, and for 3 years postpartum, with the estimated magnitude of the effect ranging between 0.5 and 3 standard deviations. Similar effects were observed when the analysis was limited to studies that excluded women with chronic hypertension, smokers, or both. Vascular dysfunction predates preeclampsia and may contribute to its pathogenesis. Future studies should address whether vascular changes that persist after preeclamptic pregnancies may represent a mechanistic link with increased risk for future cardiovascular disease.