Publications by authors named "Vasiliki Daraki"

13 Publications

  • Page 1 of 1

Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis.

Eur Thyroid J 2021 Apr 11;10(2):125-139. Epub 2020 Sep 11.

Endocrine Unit, Department of Medical Therapeutics, School of Medicine, Kapodistrian University of Athens, Athens, Greece.

Introduction: Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC.

Methods: We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported.

Results: Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates.

Conclusion: Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077374PMC
April 2021

Association of the Interleukin-6 rs1800795 Polymorphism with Type 2 Diabetes Mellitus in the Population of the Island of Crete, Greece.

Genet Test Mol Biomarkers 2018 Jul 29;22(7):448-452. Epub 2018 Jun 29.

1 Department of Internal Medicine, University Hospital of Heraklion and Laboratory of Internal Medicine-Host Defense Unit , School of Medicine, University of Crete, Heraklion, Crete, Greece .

Background: Interleukin 6 (IL-6), a proinflammatory cytokine, is elevated in patients with type 2 diabetes (T2D), and is considered an independent predictor of T2D. IL-6 single-nucleotide polymorphisms (SNPs) have been associated with higher levels of IL-6. This study investigated the role of an IL-6 gene polymorphism and its possible association to T2D in the genetically homogeneous Greek population of the island of Crete.

Materials And Methods: A total of 144 patients with T2D and 180 controls, all Cretans, selected from the Diabetes Clinic and the Department of Internal Medicine at the University Hospital of Heraklion, Crete, Greece, were genotyped for the IL-6 -174G>C (rs1800795) SNP by the restriction fragment length polymorphism method.

Results: The G/C genotype and the minor allele C of the IL-6 rs1800795 SNP were more common in individuals with T2D than controls (p = 0.004, odds ratio [OR] = 1.98, 95% confidence interval [CI]: 1.24-3.18 and p = 0.011, OR = 1.59, 95% CI: 1.11-2.26, respectively).

Conclusion: An association of the rs1800795 SNP of the IL-6 gene with T2D has been detected for the first time in Cretans. The present results, in combination with those presented previously from different ethnic/racial populations, highlight the necessity of comparative studies among different ethnic/racial populations to detect genetic characteristics and associations with T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2017.0220DOI Listing
July 2018

Postoperative day 1 levels of parathyroid as predictor of occurrence and severity of hypocalcaemia after total thyroidectomy.

Head Neck 2018 05 1;40(5):1040-1045. Epub 2018 Feb 1.

Department of Otorhinolaryngology, University of Crete Medical School, Heraklion, Crete, Greece.

Background: Hypocalcaemia is a common and serious complication after thyroidectomy. The purpose of this study is to assess the effectiveness of first postoperative day parathyroid hormone (PTH) measurement in order to predict the presence and severity of postthyroidectomy hypocalcaemia.

Methods: One hundred consecutive cases undergoing total thyroidectomy in a tertiary referral center were prospectively assessed. Preoperative measurements of PTH were compared with postoperative levels in the first morning after surgery. All cases of hypocalcaemia were recorded and evaluated with regard to preoperative and postoperative levels of PTH.

Results: A decrease of 56% of PTH levels on the first postoperative day could accurately predict postoperative hypocalcaemia with a sensitivity and specificity of 80%.

Conclusion: Serum PTH levels on the first postoperative day may be used as a reliable predictive marker for calcium supplementation need and even prolonged hospitalization in cases undergoing total thyroidectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.25081DOI Listing
May 2018

High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age: the Rhea mother-child cohort, Crete, Greece.

Eur Child Adolesc Psychiatry 2018 Jan 6;27(1):79-88. Epub 2017 Jul 6.

Department of Social Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003, Heraklion, Crete, Greece.

Animal studies suggest that prenatal vitamin D status may affect fetal brain growth. However, human studies are scarce with conflicting results. We aimed to investigate the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental outcomes at 4 years of age. We included 487 mother-child pairs from the prospective pregnancy cohort, "Rhea" in Crete, Greece. Maternal serum 25(OH) D concentrations were measured at the first prenatal visit (13 ± 2.4 weeks). Cognitive functions at 4 years were assessed by means of the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by means of Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Children of women in the high 25(OH) D tertile (>50.7 nmol/l) had 37% decreased number of hyperactivity-impulsivity symptoms (IRR 0.63, 95% CI 0.39, 0.99, p  = 0.05) and 40% decreased number of total ADHD-like symptoms (IRR 0.60, 95% CI 0.37, 0.95, p  = 0.03) at 4 years of age, compared to children of women in the low 25(OH) D tertile (<38.4 nmol/l), after adjustment for several confounders. Similar associations were found with the hyperactivity/inattention score of the SDQ questionnaire. Children of mothers with high 25(OH) D levels had also fewer total behavioral difficulties (beta-coeff: -1.25, 95% CI -2.32, -0.19) and externalizing symptoms (beta-coeff: -0.87, 95% CI -1.58, -0.15) at preschool age. The observed associations were stronger in girls than in boys (p  < 0.1). No association was observed between maternal 25(OH) D concentrations and cognitive function in preschoolers. Our results suggest that high maternal vitamin D levels in early pregnancy may protect against behavioral difficulties, especially ADHD-like symptoms at preschool age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-017-1023-xDOI Listing
January 2018

Effect of parental obesity and gestational diabetes on child neuropsychological and behavioral development at 4 years of age: the Rhea mother-child cohort, Crete, Greece.

Eur Child Adolesc Psychiatry 2017 Jun 3;26(6):703-714. Epub 2017 Jan 3.

Department of Social Medicine, Faculty of Medicine, University of Crete, PO Box 2208, 71003, Heraklion, Crete, Greece.

Studies have suggested an association between maternal obesity pre-pregnancy and gestational diabetes (GDM) with impaired offspring neurodevelopment, but it is not clear if these associations are explained by shared familiar characteristics. We aimed to assess the associations of maternal and paternal obesity, maternal glucose intolerance in early pregnancy and GDM, with offspring neurodevelopment at 4 years of age. We included 772 mother-child pairs from the "Rhea" Mother-Child cohort in Crete, Greece. Data on maternal/paternal body mass index (BMI) and maternal fasting serum samples for glucose and insulin measurements were collected at 12 weeks of gestation. GDM screening was performed at 24-28 weeks. Neurodevelopment at 4 years was assessed using the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Multivariate linear regression analyses showed that maternal obesity was associated with a significant score reduction in general cognitive ability (β-coeff -4.03, 95% CI: -7.08, -0.97), perceptual performance (β-coeff -4.60, 95% CI: -7.74, -1.47), quantitative ability (β-coeff -4.43, 95% CI: -7.68, -1.18), and executive functions (β-coeff -4.92, 95% CI: -8.06, -1.78) at 4 years of age, after adjustment for several confounders and paternal BMI. Maternal obesity was also associated with increased behavioral difficulties (β-coeff 1.22, 95% CI: 0.09, 2.34) and ADHD symptoms (β-coeff 4.28, 95% CI: 1.20, 7.36) at preschool age. Paternal obesity maternal glucose intolerance in early pregnancy and GDM was not associated with child neurodevelopment. These findings suggest that maternal obesity may impair optimal child neurodevelopment at preschool age independently of family shared characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-016-0934-2DOI Listing
June 2017

Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete).

Eur J Nutr 2018 Feb 21;57(1):209-218. Epub 2016 Sep 21.

Faculty of Medicine, University of Crete, Heraklion, Greece.

Purpose: The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults.

Methods: A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO).

Results: In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge.

Conclusions: Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00394-016-1310-1DOI Listing
February 2018

Vitamin D insufficient levels during pregnancy and micronuclei frequency in peripheral blood T lymphocytes mothers and newborns (Rhea cohort, Crete).

Clin Nutr 2017 08 27;36(4):1029-1035. Epub 2016 Jun 27.

Faculty of Medicine, University of Crete, Voutes Campus, Heraklion, Crete GR-71003, Greece.

Background & Aims: Vitamin D deficiency is common among pregnant women and may be associated with several adverse health outcomes including cancer. Micronuclei frequency is a biomarker of early genetic effects and has been used to examine the association between genotoxic exposures and cancer. We examined maternal vitamin D levels during pregnancy in associations with micronuclei frequency in maternal blood and in cord blood.

Methods: 173 mothers and 171 newborns born between 2007 and 2008 in Heraklion (Crete, Greece) were included in the study. Between 14th and 18th weeks of gestation we collected information on maternal diet using food frequency questionnaires (FFQs). We measured maternal serum concentrations of 25-hydroxyvitamin D [25(OH)D] between the first and second trimester of pregnancy. We estimated dietary vitamin D intake using information from FFQ. After delivery we collected cord blood and maternal peripheral blood. We used the cytokinesis-block micronucleus (CBMN) assay to assess the frequencies of micronucleated cells in binucleated T lymphocytes (MNBN).

Results: Maternal insufficient serum levels of 25(OH)D (<50 nmol/L) during pregnancy were associated with increased MNBN frequency in cord blood [IRR = 1.32 (95%CI: 1.00, 1.72)]. This increase was higher for newborns with birth weight above the third quartile [≥3.500 kg; IRR = 2.21 (1.26, 3.89)]. Similarly, low levels of dietary vitamin D were associated with increased MNBN frequency in cord blood [middle tertile IRR = 1.08 (0.78, 1.47), lower tertile IRR = 1.51 (1.06, 2.14)]. Insufficient levels of vitamin D were not associated with MNBN in mothers.

Conclusion: Our results suggest that vitamin D deficiency during pregnancy increases genotoxic risks in newborns. The prevalence of vitamin D deficiency globally is high and it is important to further investigate whether vitamin D supplementation or similar interventions during pregnancy could prevent DNA damage at early stages of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2016.06.016DOI Listing
August 2017

Metabolic profile in early pregnancy is associated with offspring adiposity at 4 years of age: the Rhea pregnancy cohort Crete, Greece.

PLoS One 2015 13;10(5):e0126327. Epub 2015 May 13.

Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece.

Context: Maternal pre-pregnancy obesity may increase the risk of childhood obesity but it is unknown whether other metabolic factors in early pregnancy such as lipid profile and hypertension are associated with offspring cardiometabolic traits.

Objective: Our objective was to investigate whether fasting lipid, glucose, and insulin levels during early pregnancy and maternal pre-pregnancy weight status, are associated with offspring adiposity measures, lipid levels and blood pressure at preschool age.

Design And Methods: The study included 618 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. Pregnant women were recruited at the first prenatal visit (mean: 12 weeks, SD: 0.7). A subset of 348 women provided fasting serum samples for glucose and lipid measurements. Outcomes measures were body mass index, abdominal circumference, sum of skinfold thickness, and blood pressure measurements at 4 years of age. A subsample of 525 children provided non-fasting blood samples for lipid measurements.

Results: Pre-pregnancy overweight/obesity was associated with greater risk of offspring overweight/obesity (RR: 1.83, 95%CI: 1.19, 2.81), central adiposity (RR: 1.97, 95%CI: 1.11, 3.49), and greater fat mass by 5.10 mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40 mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30 mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10 mmHg in diastolic blood pressure in early pregnancy was associated with increased risk of offspring overweight/obesity (RR: 1.22, 95%CI: 1.03, 1.45), and greater skinfold thickness by 1.71 mm (95% CI: 0.57, 2.86) at 4 years of age.

Conclusions: Metabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126327PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430416PMC
February 2016

Association of trimester-specific gestational weight gain with fetal growth, offspring obesity, and cardiometabolic traits in early childhood.

Am J Obstet Gynecol 2015 Apr 31;212(4):502.e1-14. Epub 2014 Dec 31.

Department of Social Medicine, Faculty of Medicine, University of Crete, Crete, Greece.

Objective: The purpose of this study was to investigate the association of trimester-specific gestational weight gain with offspring fetal growth, obesity risk, and cardiometabolic health outcomes from birth to 4 years of age.

Study Design: We conducted the present study with 977 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. We measured birthweight, body mass index from 6 months to 4 years of age, waist circumference, skinfold thickness, blood pressure, and blood levels of lipids, C-reactive protein, and adipose tissue hormones at 4 years of age. We used multiple linear and log Poisson regression models to examine the association of exposure with continuous or binary outcomes, respectively.

Results: Greater rate of gestational weight gain in the first trimester of pregnancy (per 200 g/wk) was associated with increased risk of overweight/obesity from 2 years (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09-1.42) to 4 years of age (RR, 1.15; 95% CI, 1.05-1.25), but not with birth size. Each 200 g/wk of weight gain in the first trimester of pregnancy was also associated with greater risk of high waist circumference (RR, 1.13; 95% CI, 1.04-1.23), high sum of skinfold thickness (RR, 1.15; 95% CI, 1.02-1.29), and higher diastolic blood pressure at 4 years of age (β, 0.43 mm Hg; 95% CI, 0.00-0.86). Greater rate of gestational weight gain during the second and third trimesters of pregnancy (per 200 g/wk) was associated with greater risk of large-for-gestational-age neonates (RR, 1.22; 95% CI, 1.02, 1.45) and higher levels of cord blood leptin (ratio of geometric means, 1.08; 95% CI, 1.00-1.17), but not with child anthropometry at later ages.

Conclusion: Timing of gestational weight gain may influence childhood cardiometabolic outcomes differentially.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081180PMC
http://dx.doi.org/10.1016/j.ajog.2014.12.038DOI Listing
April 2015

Rare presentation of occult medullary carcinoma of the thyroid as a mediastinal mass.

Hormones (Athens) 2012 Apr-Jun;11(2):210-4

Department of Endocrinology, Diabetes Mellitus and Metabolic Disorders, University of Crete, School of Medicine, Heraklion, Crete, Greece.

Objective: To describe a rare case of occult (<1 cm in diameter) medullary thyroid carcinoma (MTC) in a 45-year-old woman, presenting as an asymptomatic mediastinal mass.

Design: The diagnostic methodology included laboratory measurements of relevant biochemical and hormonal parameters including calcitonin (CT), carcinoembryonic antigen (CEA) and chromogranin A, and imaging techniques including ultrasound (U/S), computed tomography (C/T), magnetic resonance imaging (MRI) and radio labeled somatostatin analog ((111)In-DTPA-octreotide).

Results: Chest CT revealed a mediastinal mass measuring 5 cm in diameter abutting the right thyroid lobe. CEA was elevated and an association with thyroid malignancies was considered. CT was found to be markedly elevated, pointing to the diagnosis of MTC metastatic to the mediastinum. The patient underwent total thyroidectomy, lymph node dissection and removal of the mediastinal mass. Histological examination revealed MTC of the right thyroid lobe measuring 0.5 cm, metastatic to regional and superior mediastinal lymph nodes.

Conclusions: Occult MTC can infrequently present as an asymptomatic mediastinal mass. Elevated serum CT and CEA along with imaging techniques leads to the correct diagnosis and surgical management of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14310/horm.2002.1350DOI Listing
June 2013

First- and Second-Trimester Reference Intervals for Thyroid Hormones during Pregnancy in "Rhea" Mother-Child Cohort, Crete, Greece.

J Thyroid Res 2011 4;2011:490783. Epub 2011 Dec 4.

Department of Social Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003 Heraklion, Greece.

Estimation and interpretation of thyroid function tests in pregnant women is of utmost importance for maternal, fetal and neonatal health. Our objective was to calculate laboratory- and geography-specific reference intervals for thyroid hormones during pregnancy in an iodine-sufficient area of the Mediterranean, Crete, Greece. This project was performed in the context of "Rhea" mother-child cohort. Fulfillment of extensive questionnaires and estimation of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and antithyroid antibodies were performed. The reference population was defined using inclusion criteria regarding thyroidal, obstetric, and general medical status of women. Reference interval for TSH was 0.05-2.53 μIU/mL for the first and 0.18-2.73 μIU/mL for the second trimester. 6,8% and 5,9% of women in the first and second trimester, respectively, had TSH higher than the upper reference limit. These trimester-specific population-based reference ranges are essential in everyday clinical practice for the correct interpretation of thyroid hormone values and accurate classification of thyroid disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4061/2011/490783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235891PMC
August 2012

Metabolic syndrome in early pregnancy and risk of preterm birth.

Am J Epidemiol 2009 Oct 27;170(7):829-36. Epub 2009 Aug 27.

Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.

The authors determined the association between metabolic syndrome in early pregnancy (mean, 11.96 weeks) and the risk of preterm birth in the mother-child cohort study ("Rhea" Study) in Crete, Greece, 2007-2009. Maternal fasting serum samples were collected, and blood pressure was measured at the time of the first major ultrasound examination (n = 625). Multivariable log-binomial regression models were used. Women with metabolic syndrome were at high risk for preterm birth (relative risk (RR) = 2.93, 95% confidence interval (CI): 1.53, 5.58), with the highest risk observed for medically indicated preterm births (RR = 5.13, 95% CI: 1.97, 13.38). Among the components of metabolic syndrome, the most significant risk factor was hypertension (RR = 2.32, 95% CI: 1.28, 4.20). An elevation of 10 mm Hg in diastolic blood pressure increased the relative risk for preterm birth by 29% (RR = 1.29, 95% CI: 1.08, 1.53), while a per unit increase in the low density lipoprotein/high density lipoprotein cholesterol ratio increased this risk by 19% (RR = 1.19, 95% CI: 1.02, 1.39). Fetal weight growth restriction was associated with elevated levels of insulin (RR = 1.14, 95% CI: 1.08, 1.20) and diastolic blood pressure (RR = 1.27, 95% CI: 1.00, 1.61) in early pregnancy. These findings suggest that women with metabolic syndrome in early pregnancy had higher risk for preterm birth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwp211DOI Listing
October 2009