Deep venous thrombosis in patients with atresia of the inferior vena cava and right kidney hypoplasia (KILT syndrome): Systematic review of the literature.

Inferior vena cava (IVC) anomalies are uncommon congenital causes of deep vein thrombosis (DVT). KILT syndrome (kidney and IVC abnormalities with leg thrombosis) has only been described as case reports in the literature. Therefore, the characteristics, evaluation, and management of patients with KILT syndrome have not yet been standardized. This study aimed to systematically review and analyze the clinical and radiographic data and treatment of previously reported cases of KILT syndrome. In this systematic review, we performed a literature search of the PubMed, Scopus, and Web of Science databases in December 2023, with no restrictions on the publication date. After duplicate extractions, 4195 articles were screened. Case reports and case series reporting on KILT syndrome were included. In addition to previously published cases, we included a new case of a previously healthy 25-year-old man with KILT syndrome in the analysis. A total of 34 cases were therefore included in this study. The majority (76.5%) were male patients with a median age of 24 years. In most patients, unprovoked bilateral iliofemoral thrombosis was diagnosed, and 64.7% had left kidney abnormalities. Our study suggests that anomalies of the IVC should be suspected in all young patients, especially male patients, with proximal, recurrent, or idiopathic DVT. If an IVC anomaly is confirmed, the kidneys should be examined to monitor and preserve healthy kidneys in cases of KILT syndrome. The data collected from all patients emphasize the requirement of long-term anticoagulation and risk factor control. Surgical measures may be effective for treating symptomatic refractory cases.

Venous thromboembolism in patients with acute myeloid leukemia: development of a predictive model.

BACKGROUND: Patients with acute myeloid leukemia (AML) are at increased risk of venous thromboembolic events (VTE). However, thromboprophylaxis is largely underused. OBJECTIVES: This study aimed to determine possible VTE development risk factors and to develop a novel predictive model. METHODS: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. We used univariate and multivariable logistic regression to estimate binary outcomes and identify potential predictors. Based on our final model, a dynamic nomogram was constructed with the goal of facilitating VTE probability calculation. RESULTS: Out of 626 eligible patients with AML, 72 (11.5%) developed VTE during 6 months of follow-up. Six parameters were independent predictors: male sex (odds ratio [OR] 1.82, 95% confidence interval [CI]: 1.077-2.065), prior history of thrombotic events (OR 2.27, 95% CI: 1.4-4.96), international normalized ratio (OR 0.21, 95% CI: 0.05-0.95), Eastern Cooperative Oncology Group performance status (OR 0.71, 95% CI: 0.53-0.94), and intensive therapy (OR 2.05, 95% CI: 1.07-3.91). The C statistics for the model was 0.68. The model was adequately calibrated and internally validated. The decision-curve analysis suggested the use of thromboprophylaxis in patients with VTE risks between 8 and 20%. CONCLUSION: We developed a novel and convenient tool that may assist clinicians in identifying patients whose VTE risk is high enough to warrant thromboprophylaxis.

Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) represent a frequent cause of pediatric kidney failure. CNVs, as a major class of genomic variations, can also affect miRNA regions. Common CNV corresponding miRNAs (cCNV-miRNAs) are functional variants regulating crucial processes which could affect urinary system development. Thus, we hypothesize that cCNV-miRNAs are associated with CAKUT occurrence and its expressivity. METHODS: The extraction and filtering of common CNVs, identified in control samples deposited in publicly available databases gnomAD v2.1 and dbVar, were coupled with mapping of miRNA sequences using UCSC Genome Browser. After verification of the mapped miRNAs using referent miRBase V22.1, prioritization of cCNV-miRNA candidates has been performed using bioinformatic annotation and literature research. Genotyping of miRNA gene copy numbers for MIR9-3, MIR511, and MIR1299, was conducted on 221 CAKUT patients and 192 controls using TaqMan™ technology. RESULTS: We observed significantly different MIR9-3 and MIR1299 gene copy number distribution between CAKUT patients and controls (Chi-square, P = 0.006 and P = 0.0002, respectively), while difference of MIR511 copy number distribution showed nominal significance (Chi-square, P = 0.027). The counts of less and more than two of MIR1299 copy numbers were more frequent within CAKUT patients compared to controls (P = 0.01 and P = 0.008, respectively) and also in cohort of patients with anomalies of the urinary tract compared to controls (P = 0.016 and P = 0.003, respectively). CONCLUSIONS: Copy number variations of miRNA genes represent a novel avenue in clarification of the inheritance complexity in CAKUT and provide potential evidence about the association of common genetic variation with CAKUT phenotypes.

Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia.

Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30 × 109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p = 0.047) and high percentage of BM blasts (p = 0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population.

The Role of the Spleen and the Place of Splenectomy in Autoimmune Hemolytic Anemia-A Review of Current Knowledge.

Autoimmune hemolytic anemia (AIHA) is a rare, very heterogeneous, and sometimes life-threatening acquired hematologic disease characterized by increased red blood cell (RBC) destruction by autoantibodies (autoAbs), either with or without complement involvement. Recent studies have shown that the involvement of T- and B-cell dysregulation and an imbalance of T-helper 2 (Th2) and Th17 phenotypes play major roles in the pathogenesis of AIHA. AIHA can be primary (idiopathic) but is more often secondary, triggered by infections or drug use or as a part of other diseases. As the location of origin of autoAbs and the location of autoAb-mediated RBC clearance, as well as the location of extramedullary hematopoiesis, the spleen is crucially involved in all the steps of AIHA pathobiology. Splenectomy, which was the established second-line therapeutic option in corticosteroid-resistant AIHA patients for decades, has become less common due to increasing knowledge of immunopathogenesis and the introduction of targeted therapy. This article provides a comprehensive overview of current knowledge regarding the place of the spleen in the immunological background of AIHA and the rapidly growing spectrum of novel therapeutic approaches. Furthermore, this review emphasizes the still-existing expediency of laparoscopic splenectomy with appropriate perioperative thromboprophylaxis and the prevention of infection as a safe and reliable therapeutic option in the context of the limited availability of rituximab and other novel therapies.

Clinical Guidelines for Routine Neuromonitoring in Neonatal and Pediatric Patients Supported on Extracorporeal Membrane Oxygenation.

DISCLAIMER: These guidelines for routine neuromonitoring in neonatal and pediatric patients supported on extracorporeal membrane oxygenation (ECMO) are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing extracorporeal life support (ECLS)/ECMO and describe what are believed to be useful and safe practice for ECLS and ECMO but these are not necessarily consensus recommendations. The aim of clinical guidelines was to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge, and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or being deemed inclusive of all proper methods of care nor exclusive of other methods of care directed at obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient considering all the circumstances presented by the individual patient, and the known variability and biologic behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

Relapse of Evans syndrome following BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine: case report and literature review.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccines are considered to be safe. Only few cases of vaccine-induced immune thrombocytopenia or immune hemolysis have been reported so far. Evans syndrome (ES) is a very rare syndrome characterized mainly by warm autoimmune hemolytic anemia (wAIHA) and immune thrombocytopenia (ITP). CASE PRESENTATION: We present a case of a 47-year-old male with a history of wAIHA, diagnosed in 1995 and successfully treated with glucocorticoids, with sustained remission. ITP was diagnosed in May 2016. Due to refractoriness to glucocorticoids, intravenous immunoglobulins (IVIGs), azathioprine and vinblastine, he was splenectomised in April 2017, resulting in complete remission. In May 2021, eight days after the second dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine, he experienced mucocutaneous bleeding. Blood tests showed platelet count (PC) of 8×109/L, while his hemoglobin (Hb) was normal (153 g/L). He was treated with prednisone and azathioprine, without response. On day 28 after vaccine administration, weakness, jaundice and dark brown urine occurred. His laboratory tests: PC 27×109/L, Hb 45 g/L, reticulocytes 10.4%, total bilirubin 106.6 µmol/L, direct bilirubin 19.8 µmol/L, lactate dehydrogenase 633 U/L, haptoglobin ˂0.08 g/L, and positive Coombs test were consistent with ES relapse. After treatment with glucocorticoids, azathioprine and IVIGs, his blood count finally improved (PC 490×109/L, Hb 109 g/L) and remained stable on day 40 of hospitalization. CONCLUSIONS: Although it is unclear whether the relationship between COVID-19 vaccination and relapse of ES in our patient is coincidental or causal, it highlights the need for monitoring of serious outcomes following vaccination.

Arterial Thrombosis in Patients with Acute Myeloid Leukemia: Incidence and Risk Factors.

BACKGROUND: Patients with hematological malignancies have an increased risk of arterial thrombotic events (ATEs) after diagnosis, compared to matched controls without cancer. However, data about incidence and risk factors for ATE development in patients with acute myeloid leukemia (AML) are missing. AIM: The objectives of this study were to determine the incidence of ATE in non-promyelocytic-AML patients and to define the potential risk factors for ATE development. METHODS: We conducted a retrospective cohort study of adult patients with newly diagnosed AML. The primary outcome was the occurrence of confirmed ATE, defined as myocardial infarction, stroke or critical limb ischemia. RESULTS: Out of 626 eligible AML patients, 18 (2.9%) patients developed ATE in the median time of 3 (range: 0.23-6) months. Half of these patients died due to ATE complications. Five parameters were predictors of ATE: BMI > 30 (p = 0.000, odds ratio [OR] 20.488, 95% CI: 6.581-63.780), prior history of TE (p = 0.041, OR 4.233, 95% CI: 1.329-13.486), presence of comorbidities (p = 0.027, OR 5.318, 95% CI: 1.212-23.342), presence of cardiovascular comorbidities (p < 0.0001, OR 8.0168, 95% CI: 2.948-21.800) and cytogenetic risk score (p = 0.002, OR 2.113, 95% CI: 1.092-5.007). CONCLUSIONS: Our study showed that patients with AML are at increased risk of ATE. The risk was increased in patients with cardiovascular comorbidities, previous thrombosis, adverse cytogenetic risk as well as BMI > 30.

Downregulation of fibrosis related hsa-miR-29c-3p in human CAKUT.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent structural and functional urinary system malformations and take place as one of the most common congenital malformations with an incidence of 1:500. Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and chronic kidney diseases in the pediatric CAKUT. We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. We constructed interaction network of hsa-miR-101-3p, hsa-miR-101-5p and hsa-miR-29c-3p that showed significant association with fibrosis. The top enriched molecular pathway was extracellular matrix-receptor interaction (adjusted p = .0000263). We experimentally confirmed expression of three miRNAs (hsa-miR-29c-3p, hsa-miR-101-3p and hsa-miR-101-5p) in obstructed ureters (ureteropelvic junction obstruction and primary obstructive megaureter) and vesicoureteral reflux. The hsa-miR-29c-3p was shown to have lower expression in both patient groups compared to controls. Relative levels of hsa-miR-101-5p and hsa-miR-101-3p showed significant positive correlations in both groups of patients. Statistically significant correlation was observed between hsa-miR-101 (-3p and -5p) and hsa-miR-29c-3p only in the obstructed group. The significant downregulation of anti-fibrotic hsa-miR-29c-3p in obstructive CAKUT could explain activation of genes involved in fibrotic processes. As miRNAs are promising candidates in therapeutic approaches our results need further measurement of fibrotic markers or assessment of extent of fibrosis and functional evaluation of hsa-miR-29c.

Long-Term Quality of Life in Congenital Heart Disease Surgical Survivors: Multicenter Retrospective Study of Surgical and ICU Explanatory Factors.

OBJECTIVES: Greater congenital heart disease (CHD) complexity is associated with lower health-related quality of life (HRQOL). There are no data on the association between surgical and ICU factors and HRQOL in CHD survivors. This study assess the association between surgical and ICU factors and HRQOL in child and adolescent CHD survivors. DESIGN: This was a corollary study of the Pediatric Cardiac Quality of Life Inventory (PCQLI) Testing Study. SETTING: Eight pediatric hospitals participating in the PCQLI Study. PATIENTS: Patients in the study had the Fontan procedure, surgery for tetralogy of Fallot (TOF), and transposition of the great arteries (TGAs). MEASUREMENTS AND MAIN RESULTS: Surgical/ICU explanatory variables were collected by reviewing the medical records. Primary outcome variables (PCQLI Total patient and parent scores) and covariates were obtained from the Data Registry. General linear modeling was used to create the multivariable models. There were 572 patients included: mean ± sd of age 11.7 ± 2.9 years; CHD Fontan 45%, TOF/TGA 55%; number of cardiac surgeries 2 (1-9); and number of ICU admissions 3 (1-9). In multivariable models, lowest body temperature on cardiopulmonary bypass (CPB) was negatively associated with patient total score (p < 0.05). The total number of CPB runs was negatively associated with parent-reported PCQLI Total score (p < 0.02). Cumulative days on an inotropic/vasoactive drug in the ICU was negatively associated with all patient-/parent-reported PCQLI scores (p < 0.04). Neurological deficit at discharge was negatively associated with parent-reported PCQLI total score (p < 0.02). The variance explained by these factors ranged from 24% to 29%. CONCLUSIONS: Surgical/ICU factors, demographic, and medical care utilization variables explain a low-to-moderate amount of variation in HRQOL. Research is needed to determine whether modification of these surgical and ICU factors improves HRQOL, and to identify other factors that contribute to unexplained variability.

"Bridging the Gap" international ECLS training and simulation - evaluation of the 10th educational corner on EuroELSO congress 2022 in London, United Kingdom.

Introduction: Simulation training offers an authentic team-based learning opportunity without risk to real patients. The Educational Corner at the annual congress of the European Branch of Extracorporeal Life Support Organisation (EuroELSO) provided an opportunity for multiple simulation training sessions facilitated by experts from all over the world.Aim: We aimed to review the educational impact of EuroELSO Educational Corner and whether it provides a quality ECLS training to a wide spectrum of multidisciplinary international attendees utilising high and low fidelity simulation, workshops and hands on sessions.Methods: During the congress, 43 sessions were conducted dedicated to ECLS education with identified educational objectives. The sessions focused on management of adults and children on V-V or V-A ECMO. Adult sessions covered emergencies on mechanical circulatory support with management of LVAD and Impella, managing refractory hypoxemia on V-V ECMO, emergencies on ECMO, renal replacement therapy on ECMO, V-V ECMO, ECPR cannulation and performing perfect simulation. Paediatric sessions covered ECPR neck and central cannulation, renal replacement on ECMO, troubleshooting, cannulation workshop, V-V recirculation, ECMO for single ventricle, PIMS-TS and CDH, ECMO transport and neurological injury.Results: The Educational Corner was attended by more than 400 participants over the two congress days. Majority of responders (88%) reported that training sessions met the set educational goals and objectives and that this would change their current practice. Almost all (94%) reported that they received useful information and 95% would recommend the session to their colleagues.Conclusion: The Educational Corner, as an integral component of the annual EuroELSO congress, achieved the set educational goals and provided quality education based on the recipient survey. Structured multidisciplinary ECLS education with standardised curriculum and feedback is an important key step in delivering quality training to an international audience. Standardisation of European ECLS education remains an important focus of the EuroELSO.

Screening of Antifungal Activity of Essential Oils in Controlling Biocontamination of Historical Papers in Archives.

The main challenge in controlling the microbiological contamination of historical paper is finding an adequate method that includes the use of cost-effective, harmless, and non-toxic biocides whose effectiveness is maintained over time and without adverse effects on cultural heritage and human health. Therefore, this study demonstrated the possibility of using a non-invasive method of historical paper conservation based on plant essential oils (EOs) application. Evaluation of antimicrobial effects of different EOs (lemongrass, oregano, rosemary, peppermint, and eucalyptus) was conducted against Cladosporium cladosporoides, Aspergillus fumigatus, and Penicillium chrysogenum, which are commonly found on archive papers. Using a mixture of oregano, lemongrass and peppermint in ratio 1:1:1, the lower minimal inhibition concentration (0.78%) and better efficiency during a vapour test at the highest tested distance (5.5 cm) compared with individual EOs was proven. At the final step, this EOs mixture was used in the in situ conservation of historical paper samples obtained from the Archives of Vojvodina. According to the SEM imaging, the applied EOs mixture demonstrates complete efficiency in the inhibition of fungi colonization of archive papers, since fungal growth was not observed on samples, unlike the control samples.

International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe.

BACKGROUND: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. OBJECTIVE: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. METHODS: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. RESULTS: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS (n = 88, 66.2%), electroencephalography (n = 52, 39.1%), transcranial Doppler (n = 38, 28.5%) and brain injury biomarkers (n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority (n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. CONCLUSIONS: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.

Factors Predicting Malignant Occurrence and Polyp Recurrence after the Endoscopic Resection of Large Colorectal Polyps: A Single Center Experience.

Background: The aim of this study was to identify risk factors contributing to the malignancy of colorectal polyps, as well as risk factors for recurrence after the successful endoscopic mucosal resection of large colorectal polyps in a referral center. Materials and Methods: This retrospective cohort study was performed in patients diagnosed with large (≥20 mm diameter) colorectal polyps and treated in the period from January 2014 to December 2019 at the University Hospital Medical Center Bezanijska Kosa, Belgrade, Serbia. Based on the endoscopic evaluation and classification of polyps, the following procedures were performed: en bloc resection, piecemeal resection or surgical treatment. Results: A total of 472 patients with large colorectal polyps were included in the study. The majority of the study population were male (62.9%), with a mean age of 65.7 ± 10.8 years. The majority of patients had one polyp (73.7%) less than 40 mm in size (74.6%) sessile morphology (46.4%), type IIA polyps (88.2%) or polyps localized in the descending colon (52.5%). The accessibility of the polyp was complicated in 17.4% of patients. En bloc resection was successfully performed in 61.0% of the patients, while the rate of piecemeal resection was 26.1%. Due to incomplete endoscopic resection, surgery was performed in 5.1% of the patients, while 7.8% of the patients were referred to surgery directly. Hematochezia (p = 0.001), type IIB polyps (p < 0.001) and complicated polyp accessibility (p = 0.002) were significant independent predictors of carcinoma presence in a multivariate logistic regression analysis. Out of the 472 patients enrolled in the study, 364 were followed after endoscopic resection for colorectal polyp recurrence, which was observed in 30 patients (8.2%) during follow-up. Piecemeal resection (p = 0.048) and incomplete resection success (p = 0.013) were significant independent predictors of polyp recurrence in the multivariate logistic regression analysis. Conclusions: Whenever an endoscopist encounters a complex colorectal lesion (i.e., a polyp with complicated accessibility), polyp size > 40 mm, the Laterally Spreading Tumor nongranular (LST-NG) morphological type, type IIB polyps or the presence of hematochezia, malignancy risk should be considered before making the decision to either resect, refer to an advanced endoscopist or perform surgery.

Detection of impaired renal allograft function in paediatric and young adult patients using arterial spin labelling MRI (ASL-MRI).

The study aimed to discriminate renal allografts with impaired function by measuring cortical renal blood flow (cRBF) using magnetic resonance imaging arterial spin labelling (ASL-MRI) in paediatric and young adult patients. We included 18 subjects and performed ASL-MRI on 1.5 T MRI to calculate cRBF on parameter maps. cRBF was correlated to calculated glomerular filtration rate (GFR) and compared between patient groups with good (GFR ≥ 60 mL/min/1.73 m2) and impaired allograft function (GFR < 60 mL/min/1.73 m2). Mean cRBF in patients with good allograft function was significantly higher than in patients with impaired allograft function (219.89 ± 57.24 mL/min/100 g vs. 146.22 ± 41.84 mL/min/100 g, p < 0.008), showing a highly significant correlation with GFR in all subjects (r = 0.75, p < 0.0001). Also, the diffusion-weighted imaging (DWI-MRI) apparent diffusion coefficient (ADC) and Doppler measurements of peak-systolic and end-diastolic velocities and the resistive index (PS, ED, RI) were performed and both methods showed no significant difference between groups. ADC implied no correlation with GFR (r = 0.198, p = 0.464), while PS indicated moderate correlation to GFR (r = 0.48, p < 0.05), and PS and ED moderate correlation to cRBF (r = 0.58, p < 0.05, r = 0.56, p < 0.05, respectively). Cortical perfusion as non-invasively measured by ASL-MRI differs between patients with good and impaired allograft function and correlates significantly with its function.

Leaf-surface guaianolides from Amphoricarpos neumaeyri showing protective effect on human lymphocytes DNA.

Analysis of composition of CH2Cl2 surface extract of leaves of Amphoricarpos neumayeri Vis. revealed 16 sesquiterpene lactones with guaianolide skeleton, so called amphoricarpolides, typical for this genus. Four of them, 13-16, were new derivatives and their structures were elucidated by detailed analyses of IR, NMR and MS data. Amphoricarpolide (9), its 15-O-acetyl derivative (5), and two 9ß-hydroxyamphoricarpolides, 3,15-di-O-acetyl- and 3-O-acetyl-15-O-isovaleroyl derivatives (3 and 6, respectively) were tested for in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using cytochalasin-B blocked micronucleus (CBMN) assay. The tested compound exerted a beneficial effect by decreasing DNA damage of human lymphocytes.

Chemical Characterization and Antibacterial Activity of Essential Oil of Medicinal Plants from Eastern Serbia.

The objective of this study was to evaluate wild growing Satureja kitaibelii, Thymus serpyllum, Origanum vulgare, Achillea millefolium and Achillea clypeolata with respect to their essential oil (EO) content, composition and antimicrobial activity. The five species were collected at Mt. Rtanj and the village of Sesalac, Eastern Serbia. The main EO constituents of Lamiaceae plants were p-cymene (24.4%), geraniol (63.4%) and germacrene D (21.5%) in Satureja kitaibelii, Thymus serpyllum and Origanum vulgare ssp. vulgare, respectively. A. millefolium EO had multiple constituents with major ones being camphor (9.8%), caryophyllene oxide (6.5%), terpinen-4-ol (6.3%) and 1,8-cineole (5.6%), while the main EO constituents of A. clypeolata were 1,8-cineole (45.1%) and camphor (18.2%). Antimicrobial testing of the EO showed that Staphylococcus aureus (Gram-positive) was more sensitive to all of the tested EOs than Escherichia coli (Gram-negative). S. kitaibelii EO showed the highest antimicrobial activity against both tested bacterial strains. This is the first study to characterize the EO composition and antimicrobial activity of these five medicinal species from Eastern Serbia in comparison with comprehensive literature data. The results can be utilized by the perfumery, cosmetics, food and pharmaceutical industries, but also for healing purposes in self-medication.

Integration of dry-column flash chromatography with NMR and FTIR metabolomics to reveal cytotoxic metabolites from Amphoricarpos autariatus.

Metabolomics generate a profile of small molecules from plant extracts, which could be directly responsible for bioactivity effects. Using dry-column flash chromatography enabled a rapid and inexpensive method for the very efficient separation of plant extract with a high resolution. This separation method coupled to NMR and FTIR-based metabolomics is applied to identify bioactive natural products. OPLS multivariate analysis method, was used for correlation the chemical composition of the plant extracts, Amphoricarpos autariatus, with the results of cytotoxic activity against Human cervical adenocarcinoma cell line (HeLa) and epithelial lung cancer cell line (A549). In this way, the highest contribution to the cytotoxic activity was recorded for the guaianolide sesquiterpene lactones named amphoricarpolides. The compounds indicated as bioactive after metabolomics analysis were tested, and their cytotoxic activity were confirmed.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.