Publications by authors named "Rozeta Sokou"

30 Publications

  • Page 1 of 1

"Aggressive" Feeding of Very Preterm Neonates and Body Mass Index at School Age.

Nutrients 2021 Jun 1;13(6). Epub 2021 Jun 1.

Neonatal Clinic-NICU, University General Hospital, 41222 Larissa, Greece.

Introduction: The effects of "aggressive" neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our "aggressive" nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years.

Materials And Methods: Eighty four VPN, who received "aggressive" nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180-210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts.

Results: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4.

Conclusions: "Aggressive" and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.
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http://dx.doi.org/10.3390/nu13061901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227043PMC
June 2021

The use of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) in neonates: a systematic review.

Eur J Pediatr 2021 Jun 16. Epub 2021 Jun 16.

Laboratory of Haematology and Blood Bank Unit, School of Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

"Developmental hemostasis" refers to the dynamic process of gradual hemostatic maturation. Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis, while viscoelastic tests, thromboelastography (TEG), and rotational thromboelastometry (ROTEM) appear very promising as they provide insight more rapidly and accurately into the hemostatic potential. We systematically reviewed the literature in PubMed to examine the use of TEG and ROTEM in neonates. Our search yielded 34 studies, of which 18 concerned healthy neonates and 16 sick neonates. These viscoelastic tests have shown accelerated initiation of coagulation, increased clot strength, and increased fibrinolysis in healthy neonates compared to children and adults. Cord blood leads to a hypercoagulable state as compared to whole blood when testing is performed with TEG. Pre-term neonates have a more hypocoagulable profile, but balanced hemostasis, related to term neonates, that evolves to a more procoagulant phenotype over the first month of life. Critically ill neonates exhibit a more hypocoagulable profile as compared to healthy neonates. TEG and ROTEM have shown predictive value for bleeding events in critically ill neonates and neonates undergoing cardiopulmonary bypass or therapeutic hypothermia.Conclusion: TEG and ROTEM need to become part of the standard coagulation assessment in clinical settings in which hemostatic abnormalities are involved, as they seem to provide more rapid and accurate information regarding the hemostatic profile of the neonates. Their predictive value for bleeding events in critically ill neonates could lead to a more targeted therapy optimizing utilization of blood products. What is Known: • Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis. • TEG and ROTEM delineate more rapidly and accurately the hemostatic potential. What is New: • TEG and ROTEM have shown predictive value for bleeding events. • TEG and ROTEM may lead to a more targeted transfusion therapy optimizing utilization of blood products.
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http://dx.doi.org/10.1007/s00431-021-04154-4DOI Listing
June 2021

Rotational Thromboelastometry in Neonates Admitted to a Neonatal Intensive Care Unit: A Large Cross-sectional Study.

Semin Thromb Hemost 2021 Jun 15. Epub 2021 Jun 15.

Laboratory of Haematology and Blood Bank Unit, "Attikon" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

The aim of the present study was to assess the coagulation profile in neonatal critical illness using rotational thromboelastometry (ROTEM), and to investigate its association with disease severity and its potential prognostic role in this clinical setting. Over a period of 67 months (July 2014-February 2020) 423 critically ill neonates with confirmed or suspected sepsis, perinatal hypoxia, or respiratory distress syndrome, hospitalized in our neonatal intensive care unit were included in the study. Demographic, clinical, and laboratory data were recorded on admission day and arterial blood was analyzed on ROTEM analyzer using the standard extrinsically activated rotational thromboelastometry assay (EXTEM). Neonatal illness severity scores (Modified NEOMOD [Neonatal Multiple Organ Dysfunction] and SNAPPE [Score for Neonatal Acute Physiology with Perinatal Extension]) were calculated at the same time as ROTEM analysis. Mortality during in-hospital stay was the main outcome measure. Multivariable analyses showed that a 10 mm decrease in EXTEM clot amplitude recorded at 10 minutes (A10) is significantly associated with a higher mortality (odds ratio [OR] = 1.69, 95% confidence interval [CI]: 1.33-2.08). Higher modified NEOMOD (OR = 1.36, 95% CI: 1.26-1.47) and higher SNAPPE scores (OR = 1.06, 95% CI: 1.04-1.08) were also associated with increased mortality. The CT and A10 variables demonstrated the best prognostic performance among the EXTEM parameters for mortality (area under the curve [AUC] = 0.78; 95% CI: 0.69-0.86 and AUC = 0.76; 95% CI: 0.66-0.85, respectively), showing an optimal cut-off CT ≥63 seconds and A10 ≤37 mm. Using optimal cut-off values of the EXTEM parameters for prediction of mortality, neonates with CT ≥63 seconds were 7.4 times more likely to die (OR = 7.40, 95% CI: 3.50-15.65), while neonates with A10 ≤37 mm were 5.8 times more likely to die (OR = 5.88, 95% CI: 2.94-12.50). An EXTEM hypocoagulable profile on disease onset was shown to be an independent risk factor for in-hospital mortality in neonatal critical illness.
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http://dx.doi.org/10.1055/s-0041-1729964DOI Listing
June 2021

Theoretical knowledge and skill retention 3 and 6 months after a European Newborn Life Support provider course.

Am J Emerg Med 2021 May 20;49:83-88. Epub 2021 May 20.

Neonatal Department, Aretaieio Hospital, National and Kapodistrian University of Athens, Greece.

Introduction: The European Resuscitation Council Newborn Life Support Course (ERC- NLS) aims at training healthcare professionals, involved in perinatal care, in order to intervene efficiently and promptly to assist transition or resuscitate neonates who require help at birth. However, limited data exists for the retention of the theoretical knowledge and practical skills provided by the course. This study aims to evaluate the degree of knowledge and skill retention 3 and 6 months after the ERC-NLS provider course.

Methods: This is a prospective study. Theoretical knowledge was evaluated using the ERC-approved NLS written test (50 True/False questions). Evaluation of technical skills included performance, on an Advanced Life Support neonatal maniquin (LAERDAL), of airway management, ventilation and support of circulation (21 detailed skills). The effect of certain factors on theoretical skill retention was also evaluated.

Results: One hundred and sixteen (n = 116) participants were initially recruited in the study (12 males and 104 females). Theoretical knowledge was evaluated in 113 participants (3 participants missed follow-up appointments) and technical skills in 80 participants. The mean score for theoretical knowledge was 86.24% ± 5.3, 80.88% ± 7.43 and 80.04% ± 7.04 at baseline, at 3 and 6 months, respectively. This difference was significant among the three time points (baseline vs 3 months: p < 0.001; baseline vs 6 months: p < 0.001; 3 month's vs 6 months: p = 0.034). Although gender did not have an effect, doctors and participants of higher education yielded higher score of success. Regarding technical skills, 9 skills showed a continuous decline of performance from baseline to 6 months, while no difference existed for 12 skills.

Conclusions: Healthcare professionals after the NLS provider course retain satisfactory levels of theoretical knowledge and technical skills even at 6 months post-training, although, there is a decline compared to baseline. Further research is needed in order to establish the proper time and type of refreshment course in order to improve outcomes.
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http://dx.doi.org/10.1016/j.ajem.2021.05.048DOI Listing
May 2021

Gastric Volume Changes in Preterm Neonates during Intermittent and Continuous Feeding-GRV and Feeding Mode in Preterm Neonates.

Children (Basel) 2021 Apr 15;8(4). Epub 2021 Apr 15.

Neonatal Clinic-NICU, University General Hospital of Larissa, 41222 Larissa, Greece.

We aimed to evaluate gastric volume changes during intermittent milk feeds (IMF) and continuous milk feeds (CMF) in very premature neonates (VPN), with gastric residual volume (GRV) based on antral cross-sectional area (ACSA) measurements and to examine if there were differences in GRV between the two feeding methods. A randomized prospective clinical trial with crossover design was conducted in 31 preterm neonates (gestational age < 30 weeks). Gastric volume was assessed twice in each neonate (during IMF and CMF feeding), at 7 specific time points during a 2-h observation period by measuring ACSA changes via the ultrasound (U/S) method. There was a significantly different pattern of gastric volume changes between the two feeding methods. GRV, expressed as the median percentage of ACSA measurement at 120 min relative to the higher ACSA measurement during IMF, was found to be 3% (range 0-25%) for IMF and 50% (range 15-80%) for CMF. Neonates fed with IMF had a shorter mean gastric emptying time compared to those fed with CMF ( = 0.0032). No signs of feeding intolerance were recorded in either group during the period of observation. Our results showed that gastric volume changes and gastric emptying time in VPN, based on ACSA measurement changes, depend on the milk feeding method. No gastrointestinal complications/adverse events were noted with GRV up to 80% with CMF.
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http://dx.doi.org/10.3390/children8040300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071189PMC
April 2021

Insights into intrauterine growth restriction based on maternal and umbilical cord blood metabolomics.

Sci Rep 2021 Apr 9;11(1):7824. Epub 2021 Apr 9.

Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece.

Intrauterine growth restriction (IUGR) is a fetal adverse condition, ascribed by limited oxygen and nutrient supply from the mother to the fetus. Management of IUGR is an ongoing challenge because of its connection with increased fetal mortality, preterm delivery and postnatal pathologies. Untargeted nuclear magnetic resonance (H NMR) metabolomics was applied in 84 umbilical cord blood and maternal blood samples obtained from 48 IUGR and 36 appropriate for gestational age (AGA) deliveries. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) followed by pathway and enrichment analysis generated classification models and revealed significant metabolites that were associated with altered pathways. A clear association between maternal and cord blood altered metabolomic profile was evidenced in IUGR pregnancies. Increased levels of the amino acids alanine, leucine, valine, isoleucine and phenylalanine were prominent in IUGR pregnancies indicating a connection with impaired amino acid metabolism and transplacental flux. Tryptophan was individually connected with cord blood discrimination while 3-hydroxybutyrate assisted only maternal blood discrimination. Lower glycerol levels in IUGR samples ascribed to imbalance between gluconeogenesis and glycolysis pathways, suggesting poor glycolysis. The elevated levels of branched chain amino acids (leucine, isoleucine and valine) in intrauterine growth restricted pregnancies were linked with increased insulin resistance.
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http://dx.doi.org/10.1038/s41598-021-87323-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035183PMC
April 2021

Prospective Temporal Validation of the Neonatal Bleeding Risk (NeoBRis) Index.

Thromb Haemost 2020 Dec 24. Epub 2020 Dec 24.

Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

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http://dx.doi.org/10.1055/a-1343-3342DOI Listing
December 2020

Reply to Ghirardello et al Letter to the Editor.

Thromb Haemost 2020 Dec 9. Epub 2020 Dec 9.

Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

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http://dx.doi.org/10.1055/a-1333-7387DOI Listing
December 2020

Reference Values of Thrombolastometry Parameters in Healthy Term Neonates.

Children (Basel) 2020 Nov 26;7(12). Epub 2020 Nov 26.

Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, 157 72 Athens, Greece.

Background: Thromboelastometry (ROTEM), as a point of care test, is an attractive tool for rapid evaluation of hemostasis. Currently, no reference ranges exist for all ROTEM assays in neonates, limiting its use in this vulnerable population. The aim of the present study was: (1) to establish reference ranges for standard extrinsically activated (EXTEM), intrinsically activated (INTEM), and fibrinogen polymerization (FIBTEM) ROTEM assays in whole blood samples of healthy term neonates; (2) to determine the impact of gender, delivery mode, and hematocrit on ROTEM parameters.

Methods: EXTEM, INTEM, and FIBTEM ROTEM assays were performed simultaneously with complete blood count in 215 healthy term neonates.

Results: Reference ranges (2.5th and 97.5th percentiles) were obtained for clotting time (CT), clot formation time (CFT), α-angle, clot firmness at 10 min (A10), maximum clot firmness (MCF), and lysis index at 60 min (LI60, %). Reference ranges for EXTEM were CT 38-78 s, CFT 49-148 s, A10 40-65 mm, and MCF 47-69 mm, LI60 83-98%. For INTEM, CT 134-270 s, CFT 50-142 s, A10 41-63 mm, and MCF 48-67 mm, LI60 85-97%, and finally, for FIBTEM: CT 36-85 s, A10 9-25 mm and MCF 10-26 mm, LI60 92-100%. Hematocrit values were positively correlated with CT, CFT and negatively with A10, MCF values.

Conclusion: This study provides, for the first time, reference ranges for ROTEM EXTEM/INTEM/FIBTEM values simultaneously in healthy term neonates. The combined evaluation of ROTEM tests increases its diagnostic accuracy, contributing to the expansion of ROTEM use in the neonatal population.
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http://dx.doi.org/10.3390/children7120259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759895PMC
November 2020

Physicians' attitudes in relation to end-of-life decisions in Neonatal Intensive Care Units: a national multicenter survey.

BMC Med Ethics 2020 11 23;21(1):121. Epub 2020 Nov 23.

Neonatal Department, School of Medicine, Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background: End-of-life decisions for neonates with adverse prognosis are controversial and raise ethical and legal issues. In Greece, data on physicians' profiles, motivation, values and attitudes underlying such decisions and the correlation with their background are scarce. The aim was to investigate neonatologists' attitudes in Neonatal Intensive Care Units and correlate them with self-reported practices of end-of-life decisions and with their background data.

Methods: A structured questionnaire was distributed to all 28 Neonatal Intensive Care Units in Greece. One hundred and sixty two out of 260 eligible physicians answered anonymously the questionnaire (response rate 66%). Demographic and professional characteristics, self-reported practices and opinions were included in the questionnaire, along with a questionnaire of 12 items measuring physicians' attitude and views ranging from value of life to quality of life approach (scale 1-5).

Results: Continuation of treatment in neonates with adverse prognosis without adding further therapeutic interventions was the most commonly reported EoL practice, when compared to withdrawal of mechanical ventilation. Physicians with a high attitude score (indicative of value of quality-of-life) were more likely to limit, while those with a low score (indicative of value of sanctity-of-life) were more likely for continuation of intensive care. Physicians' educational level (p:0.097), involvement in research (p:0.093), religion (p:0.024) and position on the existing legal framework (p < 0.001) were factors that affected the attitude score.

Conclusions: Physicians presented with varying end-of-life practices. Limiting interventions in neonates with poor prognosis was strongly related to their attitudes. The most important predictors for physicians' attitudes were religiousness and belief for Greek legal system reform.
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http://dx.doi.org/10.1186/s12910-020-00555-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681959PMC
November 2020

Serum and Urinary N-Terminal Pro-brain Natriuretic Peptides as Biomarkers for Bronchopulmonary Dysplasia of Preterm Neonates.

Front Pediatr 2020 28;8:588738. Epub 2020 Oct 28.

Neonatal Department, Aretaieio Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece.

Bronchopulmonary dysplasia (BPD) is a common cause of respiratory illness in preterm newborns with high morbidity and mortality rates. At present, there are no early prognostic biomarkers that can be used in clinical practice to predict the development of BPD. In this review, we critically appraise evidence regarding the use of serum N-terminal pro-brain natriuretic peptide (NTproBNP) levels as a biomarker for BPD in neonates. Furthermore, we summarize studies assessing the feasibility of urinary NTproBNP levels as a non-invasive method to predict BPD in preterm infants. Multiple studies reported a strong association between NTproBNP serum levels and the onset of BPD. For urinary NTproBNP there is scarce evidence showing an association with BPD. Given the promising data obtained by preliminary studies, further assessment of this biomarker in both serum and urine is needed. Standardized reference values should be defined before conducting any further clinical studies.
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http://dx.doi.org/10.3389/fped.2020.588738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655774PMC
October 2020

Nucleated Red Blood Cells: Could They Be Indicator Markers of Illness Severity for Neonatal Intensive Care Unit Patients?

Children (Basel) 2020 Oct 27;7(11). Epub 2020 Oct 27.

Neonatal Intensive Care Unit, Nikaia General Hospital "Aghios Panteleimon", 184 54 Piraeus, Greece.

Background: We aimed to assess whether nucleated red blood cells (NRBCs) count could serve as a diagnostic and prognostic biomarker for morbidity and mortality in critically ill neonates.

Methods: The association between NRBCs count and neonatal morbidity and mortality was evaluated in an observational cohort of critically ill neonates hospitalized in our neonatal intensive care unit over a period of 69 months. The discriminative ability of NRBCs count as diagnostic and prognostic biomarkers was evaluated by performing the Receiver Operating Characteristics (ROC) curve analysis.

Results: Among 467 critically ill neonates included in the study, 45 (9.6%) of them experienced in-hospital mortality. No statistically significant difference was found with regards to NRBCs count between survivors and non-survivors, although the median value for NRBCs was sometimes higher for non-survivors. ROC curve analysis showed that NRBCs is a good discriminator marker for the diagnosis of perinatal hypoxia in neonates with area under the curve (AUC) [AUC 0.710; 95% confidence interval (CI), 0.660-0.759] and predominantly in preterm neonates (AUC 0.921 (95% CI, 0.0849-0.0993)) by using a cut-off value of ≥11.2%, with 80% sensitivity and 88.7% specificity. NRBCs also revealed significant prognostic power for mortality in septic neonates (AUC 0.760 (95% CI, 0.631-0.888)) and especially in preterms with sepsis (AUC 0.816 (95% CI, 0.681-0.951)), with cut-off value ≥ 1%, resulting in 81.6% sensitivity and 78.1% specificity.

Conclusion: NRBCs count may be included among the early diagnostic and prognostic markers for sick neonates.
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http://dx.doi.org/10.3390/children7110197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693309PMC
October 2020

The role of ROTEM variables based on clot elasticity and platelet component in predicting bleeding risk in thrombocytopenic critically ill neonates.

Eur J Haematol 2021 Feb 27;106(2):175-183. Epub 2020 Oct 27.

Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background: Our aim was to investigate the role of thromboelastometry (ROTEM) parameters, including maximum clot elasticity (MCE) and platelet component (PLTEM MCE and PLTEM MCF), in early prediction of bleeding events in thrombocytopenic critically ill neonates.

Material And Methods: This single-center, prospective cohort study included 110 consecutive thrombocytopenic neonates with sepsis, suspected sepsis, or hypoxia. On the first day of disease onset, ROTEM EXTEM and FIBTEM assays were performed and the neonatal bleeding assessment tool was used for the evaluation of bleeding events.

Results: Most EXTEM and FIBTEM ROTEM parameters significantly differed between neonates with (n = 77) and without bleeding events (n = 33). Neonates with bleeding events had significantly lower PLTEM MCE and PLTEM MCF values compared to those without bleeding events (P < .001). Platelet count was found to be strongly positively correlated with EXTEM A5 (Spearman's rho = 0.61, P < .001) and A10 (rho = 0.64, P < .001). EXTEM A10 demonstrated the best prognostic performance (AUC = 0.853) with an optimal cutoff value (≤37 mm) (sensitivity = 91%, specificity = 76%) for prediction of bleeding events in thrombocytopenic neonates.

Conclusions: EXTEM A5 and EXTEM A10 were found to be strong predictors of hemorrhage, compared to most ROTEM variables quantifying clot elasticity and platelet component in thrombocytopenic critically ill neonates.
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http://dx.doi.org/10.1111/ejh.13534DOI Listing
February 2021

A Risk Score for Predicting the Incidence of Hemorrhage in Critically Ill Neonates: Development and Validation Study.

Thromb Haemost 2021 Feb 24;121(2):131-139. Epub 2020 Aug 24.

Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

The aim of the study was to develop and validate a prediction model for hemorrhage in critically ill neonates which combines rotational thromboelastometry (ROTEM) parameters and clinical variables. This cohort study included 332 consecutive full-term and preterm critically ill neonates. We performed ROTEM and used the neonatal bleeding assessment tool (NeoBAT) to record bleeding events. We fitted double selection least absolute shrinkage and selection operator logit regression to build our prediction model. Bleeding within 24 hours of the ROTEM testing was the outcome variable, while patient characteristics, biochemical, hematological, and thromboelastometry parameters were the candidate predictors of bleeding. We used both cross-validation and bootstrap as internal validation techniques. Then, we built a prognostic index of bleeding by converting the coefficients from the final multivariable model of relevant prognostic variables into a risk score. A receiver operating characteristic analysis was used to calculate the area under curve (AUC) of our prediction index. EXTEM A10 and LI60, platelet counts, and creatinine levels were identified as the most robust predictors of bleeding and included them into a Neonatal Bleeding Risk (NeoBRis) index. The NeoBRis index demonstrated excellent model performance with an AUC of 0.908 (95% confidence interval [CI]: 0.870-0.946). Calibration plot displayed optimal calibration and discrimination of the index, while bootstrap resampling ensured internal validity by showing an AUC of 0.907 (95% CI: 0.868-0.947). We developed and internally validated an easy-to-apply prediction model of hemorrhage in critically ill neonates. After external validation, this model will enable clinicians to quantify the 24-hour bleeding risk.
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http://dx.doi.org/10.1055/s-0040-1715832DOI Listing
February 2021

Caffeine and Gastric Emptying Time in Very Preterm Neonates.

J Clin Med 2020 Jun 1;9(6). Epub 2020 Jun 1.

Neonatal Clinic-NICU, General Hospital "Agios Panteleimon", 18454 Piraeus, Greece.

Background: Caffeine has been commonly used for prevention and treatment of apnea-related symptoms in premature infants. However, its side effects have not been thoroughly studied. We investigated whether caffeine affects gastric motility in very-preterm (VP) neonates.

Methods: The study is a randomized crossover clinical trial. Twenty-two neonates with mean birth weight (BW) (standard deviation-SD) 1077 (229) g and mean gestational age (GA) (SD) 28.6 (2.1) weeks were recruited. Each neonate had its gastric emptying time checked twice with ultrasound assessment of changes in antral cross sectional area (ACSA). All neonates were sequentially allocated to the caffeine group (A) and the control group (B). Complications from the gastrointestinal tract were documented throughout the study.

Results: Statistically significant difference was found with regards to the gastric emptying time [median, (range)] between caffeine and control group (p = 0.040). Additionally, in the neonates with BW 1000-1500 g and GA ≥ 28 weeks, the gastric emptying time (minutes) was significantly longer during caffeine treatment [44.5 (36-68.2)] and [40 (34.5-66.5)] respectively, as compared to the gastric emptying time during no caffeine treatment [27 (24.2-30)] ( = 0.002) and [27 (24.5-30)] ( = 0.001). The incidence of gastrointestinal (GI) complications was significantly greater in neonates receiving caffeine [6 (27.%)] as compared with those without caffeine treatment [1 (4.6%)] ( = 0.039).

Conclusions: During caffeine treatment, a significantly delayed gastric emptying time was noted in all study neonates, especially in these with BW 1000-1500 g and those with GA ≥ 28 weeks. Further larger studies are necessary in order to confirm this interesting finding.
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http://dx.doi.org/10.3390/jcm9061676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356267PMC
June 2020

Erratum: Thromboelastometry Variables in Neonates with Perinatal Hypoxia.

Semin Thromb Hemost 2020 Jun 3;46(4):e1. Epub 2020 Jun 3.

Neonatal Department, National and Kapodistrian University of Athens School of Medicine, Aretaieion Hospital, Athens, Greece.

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http://dx.doi.org/10.1055/s-0040-1713395DOI Listing
June 2020

ROTEM diagnostic capacity for measuring fibrinolysis in neonatal sepsis.

Thromb Res 2020 08 20;192:103-108. Epub 2020 May 20.

Laboratory of Haematology and Blood Bank Unit, "Attiko" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Background: Hypofibrinolysis has been demonstrated in several studies in adult sepsis. Although fibrinolysis is an important and integral part of the hemostatic system, few data are available regarding its role in neonatal sepsis. Our purpose was to define fibrinolytic profiles across neonatal sepsis spectrum using rotational thromboelastometry (ROTEM).

Material And Methods: This study was performed in a Greek tertiary General Hospital during an 18 month-period and included 44 neonates with confirmed sepsis and 22 with suspected sepsis; 110 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM and APTEM assays were performed, clinical findings and laboratory data were recorded.

Results: Although most EXTEM parameters were significantly different among the 3 groups, Maximal Lysis (ML) and Lysis Index at 60 min (LI60) levels were similar (p = 0.11 and p = 0.20, respectively). Hyperfibrinolysis, as defined by ROTEM parameters, did not significantly differ among the study populations (p = 0.41). On the contrary, fibrinolysis shutdown, defined as an EXTEM LI60 ≥98%, was more common in septic neonates than in healthy (p < 0.001) and neonates with suspected sepsis (p = 0.042). A weak to moderate correlation of LI60 and ML with mortality (Spearman rho = 0.43 and - 0.40, p = 0.005 and 0.007, respectively) and SNAPE score (Spearman rho = 0.35 and - 0.33, p = 0.02 and 0.03, respectively) was noticed in sepsis group.

Conclusions: ROTEM, based on fibrinolytic parameters, showed a more frequent fibrinolysis shutdown in neonatal sepsis, but it could neither effectively discriminate septic neonates, nor predict their clinical outcome. The considerable overlap among numerical ROTEM values probably compromises their diagnostic clinical utility in neonatal sepsis.
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http://dx.doi.org/10.1016/j.thromres.2020.05.028DOI Listing
August 2020

Thromboelastometry Variables in Neonates with Perinatal Hypoxia.

Semin Thromb Hemost 2020 Jun 21;46(4):428-434. Epub 2020 May 21.

Neonatal Department, National and Kapodistrian University of Athens School of Medicine, Aretaieion Hospital, Athens, Greece.

Perinatal hypoxia is associated with an increased risk of coagulation disorders by enhancing the consumption of platelets and some clotting factors due to the associated severe hypoxemia, acidemia, and compromised oxygen and blood supply to the neonatal liver and bone marrow. Thromboelastometry (TEM), which estimates the dynamics of blood coagulation, may represent an attractive tool for studying the coagulation status of these neonates. We aimed at assessing the hemostatic profile of neonates with perinatal hypoxia using the standard extrinsically activated TEM (ex-TEM) assay. In total, 164 hospitalized neonates with perinatal asphyxia and/or fetal distress comprised the study subjects, and 273 healthy neonates served as controls. Ex-TEM assay was performed, SNAPPE (Score for Neonatal Acute Physiology Perinatal Extension) was calculated, and clinical findings and laboratory results were recorded in all study subjects. Hypoxic neonates expressed a prolonged clotting time (CT) and clot formation time (CFT) and reduced amplitude at 10 minutes (A10), α-angle, and maximum clot firmness compared with healthy neonates. Furthermore, asphyxiated neonates had a significantly prolonged CT and CFT and reduced A10 and α-angle compared with neonates with fetal distress. Hypoxic neonates demonstrate a hypocoagulable ex-TEM profile relative to healthy neonates, indicating a potential role of TEM in the early detection of coagulation derangement in perinatal hypoxia.
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http://dx.doi.org/10.1055/s-0040-1709473DOI Listing
June 2020

It is Time for a Universal Nutrition Policy in Very Preterm Neonates during the Neonatal Period? Comment on: "Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants" 2019, , 2772.

Nutrients 2020 04 2;12(4). Epub 2020 Apr 2.

Neonatal Clinic-NICU, University Hospital of Larissa, 413 34 Larissa, Greece.

We have read the article entitled "Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm infants" by Montserrat Izquierdo Renau et al [...].
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http://dx.doi.org/10.3390/nu12040980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230475PMC
April 2020

Comment on Toftlund et al.

Pediatr Allergy Immunol 2020 08 20;31(6):715-716. Epub 2020 Feb 20.

Neonatal Clinic-NICU, University Hospital of Larissa, Larissa, Greece.

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http://dx.doi.org/10.1111/pai.13221DOI Listing
August 2020

High-Risk Pregnancies and Their Impact on Neonatal Primary Hemostasis.

Semin Thromb Hemost 2020 Jun 13;46(4):435-445. Epub 2019 Dec 13.

Neonatal Department, Aretaieio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Primary hemostasis, similar to other systems in the adjusting and transitioning neonate, undergoes developmental adaptations in the first days of life. Although platelets of neonates do not differ quantitatively compared with those of adults, they functionally present with major differences, thus supporting the theory of a "hypofunctional" phenotype that is counterbalanced by high hematocrit and more potent von Willebrand factor multimers. No clinical effect of bleeding tendency has hence been established so far for healthy term neonates. However, discrepancies in functionality have been noted, associated with gestational age, with more pronounced platelet hyporesponsiveness in preterm neonates. Multiple methods of in vitro platelet function evaluation such as PFA-100/200, platelet aggregometry, flow cytometry, and cone and platelet analyzer have been used for assessment of neonatal primary hemostasis. Several pregnancies are characterized as "high-risk" when risk factors preexist in maternal history or evolve during pregnancy. These pregnancies require specialized observation as they may have unpredictable outcome. High-risk pregnancies include clinical entities such as preeclampsia, pregnancy-induced smoking during pregnancy, gestational diabetes mellitus (GDM), autoimmune diseases, and other maternal hematological conditions. In some cases, like systemic lupus erythematosus, antiphospholipid antibody syndrome, and maternal immunologically based thrombocytopenia, neonatal thrombocytopenia is regarded as a prominent hemostasis defect, while in others, like pregnancy-induced hypertension and preeclampsia, both quantitative and qualitative disorders of neonatal platelets have been reported. In other pathologies, like GDM, neonatal primary hemostasis remains vastly unexplored, which raises the need for further investigation. The extent to which primary hemostasis is affected in neonates of high-risk pregnancies is the main objective of this narrative review.
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http://dx.doi.org/10.1055/s-0039-3400258DOI Listing
June 2020

Evaluation of PFA-100 closure times in cord blood samples of healthy term and preterm neonates.

Clin Chem Lab Med 2020 03;58(4):e113-e116

Hematology- Immunohematology, Head of Haematology Laboratory-Blood Bank, Aretaieio Hospital, National and Kapodistrian University of Athens, 76 Vas. Sofias Street, 11526 Athens, Greece.

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http://dx.doi.org/10.1515/cclm-2019-0948DOI Listing
March 2020

Four Cases of Perineal Groove-Experience of a Greek Maternity Hospital.

Medicina (Kaunas) 2019 Aug 15;55(8). Epub 2019 Aug 15.

Neonatal Department, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece.

Perineal groove is a well-defined clinical entity that belongs to a broader group of anorectal malformations. It is characterized by a non-epithelialized mucous membrane that appears as an erythematous sulcus in the perineal midline, extending from the posterior vaginal fourchette to the anterior anal orifice. The defect is gradually cicatrized, unless there are complications like infection, defecation disorders, trauma, and bleeding. The differential diagnosis includes several other conditions like trauma, infection, irritant dermatitis, lichen sclerosis, and ulcerated hemangioma. Since it is a rare malformation, it is often misdiagnosed and its presence often elicits unnecessary diagnostic workup and intervention. In this respect, neonatologists, dermatologists, or pediatric surgeons may under- or overestimate it. We report four cases of perineal groove out of 2250 live births at a Greek Maternity Hospital between September 2016 and April 2019. The "high" incidence of perineal groove cases in our Department allowed us to familiarize with this rare defect and minimize our clinical interventions.
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http://dx.doi.org/10.3390/medicina55080488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724277PMC
August 2019

Umbilical Venous Catheters and Peripherally Inserted Central Catheters: Are They Equally Safe in VLBW Infants? A Non-Randomized Single Center Study.

Medicina (Kaunas) 2019 Aug 6;55(8). Epub 2019 Aug 6.

NICU, University General Hospital, 41222 Larissa, Greece.

Peripherally inserted central catheters (PICC) and umbilical venous catheters (UVC) are frequently used for vascular access in neonatal intensive care units (NICUs). While there is a significant need for these devices for critically ill neonates, there are many complications associated with their use. We aimed at investigating the incidence of UVC and PICC complications in very low birth weight (VLBW) infants. This is an observational study performed with neonates of the tertiary General Hospital of Piraeus, Greece, during an 18 month-period. Seventy-one neonates were recruited and divided into two groups: 34 neonates with PICC and 37 neonates with UVC. We recorded: Catheter dwell time, the causes of catheter removal, other complications, infections, and catheter tip colonization rates. : No significant statistical differences were noticed between the 2 study groups with regards to demographic characteristics, causes for catheter removal, catheter indwelling time or the incidence of nosocomial infection. Eleven UVC tips and no PICC tips were proved colonized ( = 0.001) following catheter removal. The incidence of complications associated with the use of UVCs and PICCs in VLBW infants did not significantly differ in our study. Their use seems to be equally safe. Further studies, with larger samples, are necessary to confirm our results.
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http://dx.doi.org/10.3390/medicina55080442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723053PMC
August 2019

Very preterm neonates receiving "aggressive" nutrition and early nCPAP had similar long-term respiratory outcomes as term neonates.

Pediatr Res 2019 12 7;86(6):742-748. Epub 2019 Aug 7.

NICU, University Hospital of Larissa, Larissa, Greece.

Backround: The impact of the consistent implementation of "aggressive" nutrition by means of intensive early neonatal nutritional support up to 40-44 weeks postmenstrual age and the use of nasal continuous positive airway pressure (nCPAP) within the first hour of life on the respiratory function of very premature neonates (VPN) at school age is unclear.

Method: Respiratory function was evaluated in 108 VPN and 70 term controls. Growth, frequency of lower respiratory tract infections, re-hospitalization, and spirometry were recorded up to 8-10 years of age. Comparison was carried out between the two study groups.

Results: There was no significant difference in forced expiratory volume in 1 s and forced vital capacity at 8 years of age, and also in lower respiratory tract infections and re-hospitalization due to them, up to 8 years of age between preterm and term neonates. No significant difference was found in spirometry measurements neither between premature neonates with and without BPD nor between the two subgroups of preterms and term neonates.

Conclusion: "Aggressive" nutrition, persistent nCPAP use, and their impact on early postnatal growth probably positively affect the respiratory function of our study population. These very encouraging results need to be confirmed by larger studies.
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http://dx.doi.org/10.1038/s41390-019-0514-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887846PMC
December 2019

Clinical Application of Thromboelastography/Thromboelastometry (TEG/TEM) in the Neonatal Population: A Narrative Review.

Semin Thromb Hemost 2019 Jul 13;45(5):449-457. Epub 2019 Jun 13.

Neonatal Department, National and Kapodistrian University of Athens, Aretaeio Hospital, Athens, Greece.

Hemostasis is a dynamic age-related process, which gradually evolves from fetal life throughout childhood until adulthood. Although at birth there is a hemostatic deficit of most coagulation factors, studies have shown that this "hemostatic immaturity" is functionally counterbalanced in healthy term or preterm newborns. This delicate hemostatic balance is, however, deranged in sick neonates, resulting in an enhanced risk of hemorrhage and/or thrombosis. In critically ill neonates, conventional coagulation tests do not seem to provide reliable information or indications regarding the functional status of platelets or fibrinolysis. In contrast, viscoelastic tests, namely thromboelastography/thromboelastometry (TEG/TEM) hold promise for rapid assessment of the whole hemostatic potential, allowing immediate intervention should this be required. However, neonatal data are limited due to lack of reference values, especially in premature neonates. In this narrative review, we provide some insights around current knowledge regarding TEG/TEM applications in healthy and sick newborns. Overall, the use of viscoelastic tests in diagnosis and management of coagulation disorders in neonates is definitely worth further exploration. Consideration should be made to include these tests in the routine laboratory investigation of neonates and specific transfusion algorithms should also be developed in order to avoid treatment pitfalls.
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http://dx.doi.org/10.1055/s-0039-1692210DOI Listing
July 2019

Thromboelastometry: studying hemostatic profile in small for gestational age neonates-a pilot observational study.

Eur J Pediatr 2019 Apr 1;178(4):551-557. Epub 2019 Feb 1.

Laboratory of Haematology and Blood Bank Unit, "Attiko" Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Scarce data exists about the hemostatic status of small for gestational age (SGA) neonates. We aimed at evaluating the hemostatic profile of SGA neonates, using thromboelastometry (TEM). This is an observational study performed in a Greek tertiary General Hospital during an 18-month period. Ninety-three neonates were included in the study: 48 appropriate for gestational age weight (AGA) neonates and 45 SGA neonates Extrinsically activated TEM (ex-TEM) parameters, such as clotting time, clot formation time, amplitude recorded at 5 and 10 min, a angle, maximum clot firmness, lysis index at 60 min, and also platelet count, were used for the evaluation of the hemostatic profile in all neonates. No statistically significant differences were noticed regarding all ex-TEM parameters between AGA and SGA neonates, while no event of hemorrhage or thrombosis was noticed in the study population.Conclusions: The coagulation system of SGA neonates seems to be fully functional, with no evident tendency toward coagulopathy or thrombosis, when compared with AGA neonates. TEM seems to provide a promising and valid assessment of coagulation and fibrinolysis systems and may be used as a valuable biomarker, in the future. Further studies, with large samples, are necessary to confirm our results. What is Known: • SGA neonates may present coagulation disorders mainly due to hepatic dysfunction, polycythemia, and thrombocytopenia owing to long-term intrauterine hypoxia. • In the literature, despite the statistically significant differences in laboratory results between SGA and AGA neonates, no clinical manifestations of significantly altered hemostasis were recorded. Data of TEM interpretation of hemostasis in SGA neonates are not available. What is New: • TEM seems to interpret coagulation mechanism of preterm and full-term SGA neonates and confirm previous relevant literature findings regarding hemostasis in these neonates.
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http://dx.doi.org/10.1007/s00431-019-03331-wDOI Listing
April 2019

Thromboelastometry for diagnosis of neonatal sepsis-associated coagulopathy: an observational study.

Eur J Pediatr 2018 Mar 18;177(3):355-362. Epub 2017 Dec 18.

Laboratory of Haematology and Blood Bank Unit, School of Medicine, "Attiko" University Hospital, National and Kapodistrian University of Athens, 1 Rimini Str, 12462, Athens, Greece.

Our aim was to evaluate the potential role of standard extrinsically activated thromboelastometry (EXTEM) assay in the early detection of neonatal sepsis. We studied 91 hospitalized neonates categorized in two groups: group A included 35 neonates with confirmed sepsis, while group B included 56 neonates with suspected sepsis; 274 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM assay was performed, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE) and Tοllner score were calculated, and clinical findings and laboratory results were recorded. Septic neonates had significantly prolonged clotting time (CT) and clot formation time (CFT), and reduced maximum clot firmness (MCF), compared to neonates with suspected sepsis (p values 0.001, 0.001, and 0.009, respectively) or healthy neonates (p values 0.001, 0.001, and 0.021, respectively). EXTEM parameters (CT, CFT, MCF) demonstrated a more intense hypocoagulable profile in septic neonates with hemorrhagic diathesis than those without (p values 0.021, 0.007, and 0.033, respectively). In septic neonates, CFT was correlated with platelet count, SNAPPE, Tollner score, and day of full enteral feeding (p values 0.01, 0.02, 0.05, and 0.03, respectively).

Conclusions: A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity. What is Known: • The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated. • Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis. What is New: • ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis. • ROTEM could be a useful tool in the early detection of sepsis in neonates.
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http://dx.doi.org/10.1007/s00431-017-3072-zDOI Listing
March 2018

Reference ranges of thromboelastometry in healthy full-term and pre-term neonates.

Clin Chem Lab Med 2017 Aug;55(10):1592-1597

.

Background: Rotational thromboelastometry (ROTEM) is an attractive method for rapid evaluation of hemostasis in neonates. Currently, no reference values exist for ROTEM assays in full-term and pre-term neonates. Our aim was to establish reference ranges for standard extrinsically activated ROTEM assay (EXTEM) in arterial blood samples of healthy full-term and pre-term neonates.

Methods: In the present study, EXTEM assay was performed in 198 full-term (≥37 weeks' gestation) and 84 pre-term infants (<37 weeks' gestation) using peripheral arterial whole blood samples.

Results: Median values and reference ranges (2.5th and 97.5th percentiles) for the following main parameters of EXTEM assay were determined in full-term infants: clotting time (seconds), 41 (range, 25.9-78); clot formation time (seconds), 70 (range, 40-165.2); maximum clot firmness (mm), 66 (range, 41-84.1); lysis index at 60 min (LI60, %), 97 (range, 85-100). The only parameter with a statistically significant difference between full-term and pre-term neonates was LI60 (p=0.006). Furthermore, it was inversely correlated with gestational age (p=0.002) and birth weight (p=0.016) in pre-term neonates.

Conclusions: In conclusion, an enhanced fibrinolytic activity in pre-term neonates was noted. For most EXTEM assay parameters, reference ranges obtained from arterial newborn blood samples were comparable with the respective values from studies using cord blood. Modified reagents, small size samples, timing of sampling, and different kind of samples might account for any discrepancies among similar studies. Reference values hereby provided can be used in future studies.
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http://dx.doi.org/10.1515/cclm-2016-0931DOI Listing
August 2017

MBL2 genotypes and their associations with MBL levels and NICU morbidity in a cohort of Greek neonates.

J Immunol Res 2015 24;2015:478412. Epub 2015 Mar 24.

Department of Immunology & Histocompatibility, School of Health Sciences, Faculty of Medicine, University Hospital of Larissa, University of Thessaly, Biopolis 3, 41500 Larissa, Greece.

The objective of this study was to assess the frequency of MBL2 genotypes and their associations with MBL levels and various morbidities of a neonatal intensive care unit (NICU). One hundred and thirty-four (134) NICU (83 term and 51 preterm) and 150 healthy neonates were enrolled in the study. MBL2 genotype and MBL serum levels at birth were determined prospectively by PCR-RFLP-sequencing and enzyme-linked immunosorbent assay, respectively. NICU neonates displayed significantly lower MBL serum levels compared to healthy ones. MBL deficiency, defined as the low MBL2 expression group (XA/O and O/O), was significantly associated with an increased risk of respiratory morbidity, especially transient tachypnea of the newborn and respiratory distress syndrome (RDS). Moreover, an increase of 100 ng/mL of serum MBL levels decreases by 5% the risk of total respiratory morbidity and by 7% the risk of RDS, after correction for prematurity and sex and regardless of the presence of infections. Our study further supports the notion that neonates with MBL deficiency and low MBL serum levels at birth may be at higher risk of developing severe respiratory complications.
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http://dx.doi.org/10.1155/2015/478412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387979PMC
January 2016
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