Publications by authors named "Vassiliki Papaevangelou"

90 Publications

Repeated Leftover Serosurvey of SARS-CoV-2 IgG Antibodies in Greece, May to August 2020.

Vaccines (Basel) 2021 May 13;9(5). Epub 2021 May 13.

Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larissa, Greece.

A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between May and August 2020. It was designed as a cross-sectional survey and was repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Of 20,110 serum samples collected, 89 (0.44%) were found to be positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (0.35%) observed in May 2020. The highest seroprevalence was primarily observed in the "30-49" year age group. Females presented higher seroprevalence compared to males in May 2020 (females: 0.58% VS males: 0.10%). This difference reversed during the study period and males presented a higher proportion in August 2020 (females: 0.12% VS males: 0.58%). Differences in the rate of seropositivity between urban areas and the rest of the country were also observed during the study period. The four-month infection fatality rate (IFR) was estimated to be 0.47%, while the respective case fatality rate (CFR) was at 1.89%. Our findings confirm low seroprevalence of COVID-19 in Greece during the study period. The young adults are presented as the most affected age group. The loss of the cumulative effect of seropositivity in a proportion of previous SARS-CoV-2 infections was indicated.
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http://dx.doi.org/10.3390/vaccines9050504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152765PMC
May 2021

Early human milk lactoferrin during SARS-CoV-2 infection.

J Matern Fetal Neonatal Med 2021 May 9:1-4. Epub 2021 May 9.

Third Department of Pediatrics, National and Kapodistrian University of Athens, University General Hospital "ATTIKON", Athens, Greece.

Background/aim: Early human milk provides protection against viral infections due to its high nutritional value, abundance of maternal antibodies and the specific role of lactoferrin (Lf). Lf blocks the early interaction between SARS-CoV-2 and host cells by binding to specific cell receptors and has been proposed as a preventative and adjunct treatment for COVID-19. This preliminary report aimed to investigate concentrations of Lf in early milk of SARS-CoV-2 positive mothers versus non-infected controls.

Material And Methods: In a cohort of 13 SARS-CoV-2 positive mothers and 15 controls, breast milk concentrations of Lf were determined by ELISA on day 3 postpartum. Additionally, colostrum samples of infected mothers were analyzed for SARS-CoV-2 RNA detection and anti-SARS-CoV-2 IgA and IgG determination using RT-qPCR and ELISA, respectively.

Results: No differences were found in breast milk Lf concentrations between SARS-CoV-2 positive mothers and controls. In a subgroup analysis, however, symptomatic mothers ( = 7) presented with lower breast milk Lf concentrations, as compared to asymptomatic mothers ( = .041) and healthy controls ( = .029). All milk samples tested negative for SARS-CoV-2 RNA. Early human milk of infected mothers displayed IgA and IgG SARS-CoV-2 specific reactivity.

Conclusions: Our data showed a different early breast milk Lf "profile" between COVID-19 symptomatic and asymptomatic mothers with the latter being at non-COVID levels (control group). SARS-CoV-2 RNA was not detected in any breast milk sample. Early human milk Lf levels are potentially influenced by the severity of maternal COVID-19 infection during pregnancy.
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http://dx.doi.org/10.1080/14767058.2021.1920010DOI Listing
May 2021

Study of Xbal and Pvull polymorphisms of estrogen receptor alpha (ERα) gene in girls with precocious/early puberty.

Endocrine 2021 May 4. Epub 2021 May 4.

Pediatric Endocrinology Unit, Third Department of Pediatrics, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Purpose: Studies examining association of estrogen receptor alpha (ERα) polymorphisms with early puberty are scarce and results are controversial; data in Caucasian girls are lacking. Main objective was to determine association of Xbal and Pvull polymorphisms of ERα gene in Greek girls with precocious/early puberty METHODS: We studied 107 girls with idiopathic precocious/early puberty and 81 young women with pubertal maturation within normal age (controls). Pubertal stage, height SDS (HSDS), and BMI z-score were determined in patients. In controls, height was measured and menarcheal age was self-reported. All participants in the study were genotyped for XbaI and PvuII polymorphisms of the ERα gene.

Results: There was no significant difference in XbaI and PvuII polymorphisms between patients and controls. Homozygous, xx and pp, girls had an earlier onset of puberty, although non-significant, than heterozygous or with no polymorphisms p = 0.9; in girls with pubertal onset <7 years, the association tended to become significant, p = 0.09. Girls with xxpp genotype were significantly taller, HSDS 1.63, p = 0.014. In controls, homozygosity for Xbal (xx) and PvuII (pp) was associated with significantly earlier menarche than in women with no polymorphism, p = 0.013 and p = 0.026, respectively, and xxpp genotype was associated with taller adult height, p = 0.017.

Conclusion: XbaI and PvuII polymorphisms are not related to idiopathic precocious/early puberty. Early pubertal girls homozygous for both polymorphisms presented earlier onset of puberty, although statistically non-significant, and taller height than girls heterozygous or without these polymorphisms. Homozygosity for both polymorphisms is associated with earlier menarche and taller adult height.
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http://dx.doi.org/10.1007/s12020-021-02695-0DOI Listing
May 2021

Congenital cytomegalovirus infection: do pregnant women and healthcare providers know enough? A systematic review.

J Matern Fetal Neonatal Med 2021 May 4:1-10. Epub 2021 May 4.

Department of Paediatrics, Patras Medical School, Rion, Greece.

Background: Cytomegalovirus (CMV) is the most frequent cause of congenital infection worldwide causing serious morbidity in newborns, infants, and children. Despite the clinical importance of congenital CMV (cCMV), studies conducted so far conclude that there is limited awareness in both the medical community and public of cCMV infection. The aim of this systematic review was to assess the knowledge and awareness of cCMV among pregnant women and healthcare providers during the last decade.

Methods: A literature search was performed in PubMed and Scopus, including studies published between 2011 and 2020. Eligibility criteria included articles focusing on either pregnant women or healthcare providers and reporting data about cCMV awareness. We included cross-sectional and interventional studies. Study quality was assessed using the Study Quality Assessment Tools by National Institute of Health.

Results: Overall, 23 studies fulfilled the inclusion criteria, 13 studies referred to pregnant women and 10 to healthcare providers. A total of 6521 pregnant women and 3609 healthcare providers were included. The level of awareness of pregnant women about cCMV was low to moderate. However, pregnant women showed willingness to adopt hygiene strategies following interventional-educational practices. Concurrently, awareness among healthcare providers varied depending on the specialty. Nonetheless, a great proportion admitted feeling inadequate in advising pregnant women for cCMV screening and prevention.

Conclusion: The role of healthcare providers in growing awareness among pregnant women is of paramount importance. Due to the lack of an effective vaccine as yet, education of women regarding hygiene measures is currently the best strategy to prevent cCMV disease.
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http://dx.doi.org/10.1080/14767058.2021.1918088DOI Listing
May 2021

Reducing Duration of Antibiotic Use for Presumed Neonatal Early-Onset Sepsis in Greek NICUs. A "Low-Hanging Fruit" Approach.

Antibiotics (Basel) 2021 Mar 9;10(3). Epub 2021 Mar 9.

Infectious Diseases Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens (NKUA), 11527 Athens, Greece.

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and -resource intervention to reduce antibiotic use in Greek NICUs implementing a "low-hanging fruit" approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016-06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase ( = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend ( = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days ( = 0.001, 95%CI [-45.33, -12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a "low-hanging fruit" approach. In resource-limited settings, similar targeted stewardship interventions can be applied.
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http://dx.doi.org/10.3390/antibiotics10030275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000600PMC
March 2021

Mycobacterium marseillense lymphadenitis: A newly identified strain in the pediatric population.

Infect Dis Now 2021 Mar 30. Epub 2021 Mar 30.

Third department of pediatrics, Attikon University General Hospital, National and Kapodistrian University of Athens, Rimini 1, Chaidari, 12642 Athens, Greece.

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http://dx.doi.org/10.1016/j.idnow.2021.03.008DOI Listing
March 2021

Is Hepatobiliary Scintigraphy Sufficient to Diagnose Rotor Syndrome in a 3-Year-Old Boy?

J Nucl Med Technol 2021 Jun 15;49(2):193-194. Epub 2021 Mar 15.

Third Department of Pediatrics, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Rotor syndrome (RS) is a benign, inherited, commonly misdiagnosed cause of conjugated hyperbilirubinemia whose identification prevents unnecessary invasive investigations. We present the case of a 3-y-old boy with phenotypic and laboratory findings of RS but negative genetic test results, whose diagnosis was confirmed by hepatobiliary scintigraphy.
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http://dx.doi.org/10.2967/jnmt.120.257618DOI Listing
June 2021

First case of peritonitis and acute pancreatitis related to Toxocara infection in a previously healthy 5-year-old boy.

J Paediatr Child Health 2021 Mar 8. Epub 2021 Mar 8.

Third Department of Pediatrics, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

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http://dx.doi.org/10.1111/jpc.15438DOI Listing
March 2021

Seroprevalence of Hepatitis C in Children Without Identifiable Risk-Factors: A Systematic Review and Meta-Analysis.

J Pediatr Gastroenterol Nutr 2021 Jun;72(6):e140-e148

Third Department of Pediatrics, National and Kapodistrian University of Athens, School of Medicine, University General Hospital ATTIKON, Athens, Greece.

Objectives: Hepatitis C virus (HCV) remains a major public health burden for >30 years since its discovery. It is estimated that >80 million people have been already infected. Direct-acting antiviral (DAA) treatment is now approved for young children over the age of 3 years. Treating children before the development of high-risk behaviors is optimal. Thus, assessing the current epidemiology of HCV in children becomes important and may promote awareness.

Methods: Articles describing the prevalence of hepatitis C in children, were systematically reviewed. To assess HCV infection prevalence in the general population, studies discussing high-risk groups alone were excluded.

Results: Data from 58 studies were analyzed. National data was scarce. An overall prevalence of HCV in children of 0.87% was found, ranging from 0.34% in Europe to 3.02% in Africa. Prevalence of viremic infection is important and data synthesis from available data indicated that HCV viremia was detected in 56.8% of children. The prevalence of HCV according to sex was described in 25 studies but no difference between sexes was detected. HCV prevalence was significantly higher in children older than 10 years (0.97%) when compared to those ages under 10 years old (0.75%, P < 0.001).

Conclusions: Considering probable underdiagnosis of HCV infection in children, this information reveals that prevalence is substantial. One may argue that future strategies aiming towards HCV elimination, may need to include antiviral treatment of pre-adolescent children as well.
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http://dx.doi.org/10.1097/MPG.0000000000003099DOI Listing
June 2021

SARS-CoV-2 molecular testing in Greek hospital paediatric departments: a nationwide study.

Epidemiol Infect 2021 02 24;149:e70. Epub 2021 Feb 24.

3rd Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

As most children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present with mild symptoms or they are asymptomatic, the optimal strategy for molecular testing it is not well defined. The aim of the study was to determine the extent and aetiology of molecular testing for SARS-CoV-2 in Greek paediatric departments during the first phase of the pandemic and identify possible differences in incidence, depending on the age group and geographical area. We conducted a nationwide study of molecular testing for SARS-CoV-2 of children in paediatric departments between March and June 2020. A total of 65 paediatric departments participated in the study, representing 4901 children who were tested for SARS-CoV-2 and 90 (1.8%) were positive. Most paediatric cases were associated with topical outbreaks. Adolescents 11-16 years had the highest positivity rate (3.6%) followed by children 6-10 years (1.9%). However, since the testing rate significantly differed between age groups, the modified incidence of SARS-CoV-2 infection per age group was highest in infants <1 year (19.25/105 population). Most children tested presented with fever (70.9%), respiratory (50.1%) or gastrointestinal symptoms (28.1%). Significant differences were detected between public and private hospitals regarding the positivity rate (2.34% vs. 0.39%, P-value <0.001). Significant variation in SARS-CoV-2 molecular testing positivity rate and incidence between age groups indicate discrepancies in risk factors among different age groups that shall be considered when ordering molecular testing.
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http://dx.doi.org/10.1017/S0950268821000455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985887PMC
February 2021

Colchicine-Induced Macrophage Activation Syndrome in an Adolescent Female Patient With PSTPIP1-Associated Myeloid-Related Proteinemia Inflammatory Syndrome.

J Clin Rheumatol 2020 Jun 9. Epub 2020 Jun 9.

Department of Pediatrics Attikon General Hospital National and Kapodistrian University of Athens Athens, Greece

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http://dx.doi.org/10.1097/RHU.0000000000001407DOI Listing
June 2020

Effects of measles-containing vaccination in children with severe underlying neurologic disease.

Vaccine 2021 03 3;39(10):1481-1484. Epub 2020 Dec 3.

Third Department of Pediatrics, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Background: Measles outbreaks pose significant risk for those unvaccinated.

Patients And Methods: Measles-containing vaccine was offered to unvaccinated children with severe neurologic diseases during a measles outbreak. Vaccination adverse events were reported by parents 30 days following vaccination. Long term effects were evaluated 12 months post vaccination.

Results: Twenty-seven children were vaccinated (36 doses given). Half of parents (51.8%) reported no adverse events following immunization. Adverse events included afebrile seizures (6/36), fever alone (5/36) and febrile seizures (5/36). Two children required hospitalization. Quadrivalent measles-containing vaccine combined with varicella was associated with febrile seizures (p = 0.04). No child needed adjustment of the anti-epileptic treatment or exhibited developmental regression.

Conclusion: Ina series of children with prior severe neurologic disease, the safety-tolerability profile ofvaccines containing a measles vaccine component suggests that vaccination is justified. Main side effect was seizure aggravation in children with known epileptic disease.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.061DOI Listing
March 2021

Perianal Abscess With Stellate Lacerations in a 3.5-year-old Previously Healthy Boy.

Indian Pediatr 2020 11;57(11):1078-1079

Third Department of Pediatrics, Attikon University Hospital, Athens, Greece.

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November 2020

Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM).

J Pediatr Endocrinol Metab 2020 Dec 12;33(12):1525-1531. Epub 2020 Nov 12.

Unit of Pediatric Endocrinology and Diabetes, 3rd University Pediatric Clinic, Attikon University Hospital, Athens, Greece.

Objectives: Treatment of children with Hashimoto thyroiditis (HT) and particularly of those with coexistent diabetes mellitus type 1 (TIDM) and normal/mildly elevated serum TSH is controversial. The aim of the study was to evaluate the natural course of HT in children with TIDM compared with children with no other coexistent autoimmunity and investigate for possible predictive factors of thyroid function deterioration.

Methods: Data from 96 children with HT, 32 with T1DM (23 girls, nine boys) mean (sd) age: 10.6 (2.3) years, and 64 age and sex-matched without T1DΜ (46 girls, 18 boys), mean (sd) age: 10.2 (2.9) years were evaluated retrospectively. They all had fT4 and TSH values within normal ranges and available data for at least three years' follow-up.

Results: During the follow-up period, 11 children (34.4%) with TIDM exhibited subclinical hypothyroidism and two children (6.2%) progressed to overt hypothyroidism compared to 12 (18.8%) and two (3.1%) among children without TIDM, respectively. Among children with HT, a higher percentage (40.6%) of children with T1DM progressed to subclinical or overt hypothyroidism, compared with children (21.9%) with similar characteristics but without TIDM or other coexistent autoimmunity.

Conclusions: The annual conversion rate from euthyroidism to hypothyroidism in children with T1DM was significantly higher compared to sex and age-matched children without TIDM. Prospective randomized trials are needed to support the view of an earlier intervention therapy even in milder degrees of thyroid failure in these children.
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http://dx.doi.org/10.1515/jpem-2020-0222DOI Listing
December 2020

Breastfeeding during the novel coronavirus (COVID-19) pandemic: guidelines and challenges.

J Matern Fetal Neonatal Med 2020 Nov 8:1-7. Epub 2020 Nov 8.

Pediatric Infectious Diseases Department, Third Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece.

COVID-19 pandemic has raised questions on pregnant women and newborns' management. Guidelines, issued by most international agencies and national bodies, recommend rooming-in and direct breastfeeding. In the early days of this pandemic, breastfeeding practices have been challenged by fear among both parents and healthcare workers occasionally resulting in mother-newborn separation. We herein review current breastfeeding guidelines and discuss remaining questions and challenges. As we are facing the second wave of this pandemic, more information is gathered, especially regarding possible virus transmissibility through breastfeeding, enabling more definite instructions about breastfeeding practices.
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http://dx.doi.org/10.1080/14767058.2020.1838481DOI Listing
November 2020

Use of point-of-care molecular tests reduces hospitalization and oseltamivir administration in children presenting with influenza-like illness.

J Med Virol 2021 06 8;93(6):3944-3948. Epub 2020 Oct 8.

Third Department of Pediatrics, ATTIKON University General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Influenza is associated with increased morbidity, healthcare costs, hospitalization rates, and mortality in children. Rapid immunochromatography assay (ICA), a test with low sensitivity, is often used as point-of-care (POC) test. Recently, the rapid syndromic molecular test FilmArray has become available. This observational study aims to evaluate whether the use of FilmArray would decrease the use of antivirals and hospitalization rates among children presenting to the emergency room (ER) with influenza-like illness (ILI) symptoms. Nasopharyngeal swabs were prospectively collected from children, aged 0-16 years, presenting with ILI at the ER of a tertiary hospital during the peak endemic period. Patients were allocated to be tested by either FilmArray or ICA. The use of antivirals and hospitalization rates were noted. Logistic regression models were used to investigate the impact of testing methods on decision-making. Overall, 80 children were included (mean age: 5 years). Admissions were more likely to occur if an ICA test was performed (OR, 3.16; 95% CI, 1.01-9.82; p = .046). Oseltamivir administration was more likely among children who had undergone the ICA test (OR, 4.67; 95% CI, 1.06-20.43; p = .041). The implementation of rapid molecular test had no impact on complementary diagnostic testing or antibacterial prescription. The use of FilmArray significantly reduced both hospitalization and oseltamivir administration in children. Further knowledge on the use of POC tests is required to improve current management of children presenting with ILI and decrease associated healthcare costs.
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http://dx.doi.org/10.1002/jmv.26538DOI Listing
June 2021

Preliminary Data of a Quantitative Point of Care Test for SARS-CoV-2 Antibodies From Greece.

In Vivo 2020 Sep-Oct;34(5):3039-3045

Second Department of Radiology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece

Background: Antibody testing is necessary to identify immune individuals in the post-initial wave of the COVID-19 pandemic.

Patients And Methods: We prospectively evaluated the performance of a quantitative point-of-care test (POCT) for SARS-CoV-2 antibodies. The patient group (PG) comprised of hospitalized confirmed COVID-19 cases. Asymptomatic healthcare volunteers with negative rRT-PCR were included in the control group (CG). Measurement of IgM and IgG was obtained by dry fluorescence immunoassay.

Results: Twenty-six PG (65.9±15.4 years old, male 57.7%) and 18 CG (45.6±10.1 years old, male 33.3%) were included. By manufacturer's cut-off (≥0.04 mIU/ml), sensitivity and specificity were 73.08% and 88.89% for IgM and 88.46% and 33.33% for IgG, respectively. Estimated areas under the ROC curve were 0.907 and 0.848 for IgM and IgG, respectively. Results were improved using a cut-off of IgM ≥0.05 mIU/ml and IgG ≥0.10 mIU/ml.

Conclusion: Using stringent cut-off values, SARS-CoV-2 antibody POCT detects immune people and can be used during socioeconomic normalization of communities.
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http://dx.doi.org/10.21873/invivo.12138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652506PMC
September 2020

Repeated leftover serosurvey of SARS-CoV-2 IgG antibodies, Greece, March and April 2020.

Euro Surveill 2020 08;25(31)

Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, Larissa, Greece.

A serosurvey of IgG antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) was performed during March and April 2020. Among 6,586 leftover sera, 24 (0.36%) were positive, with higher prevalence in females, older individuals and residents of large urban areas. Seroprevalence was estimated at 0.02% and 0.25%, respectively, in March and April, infection fatality rate at 2.66% and 0.54%. Our findings confirm low COVID-19 incidence in Greece and possibly the effectiveness of early measures.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.31.2001369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459271PMC
August 2020

Maternal type of CMV infection and sequelae in infants with congenital CMV: Systematic review and meta-analysis.

J Clin Virol 2020 08 27;129:104518. Epub 2020 Jun 27.

Third Department of Pediatrics, National and Kapodistrian University of Athens, School of Health Sciences, University General Hospital ATTIKON, Rimini 1, Chaidari 12462, Athens, Greece. Electronic address:

Cytomegalovirus (CMV) is the most common congenital infection. Intrauterine transmission may occur following primary (PI) or non-primary (NPI) maternal infection and result in both neonatal symptomaticdisease and long-term complications.The aim of the present systematic review and meta-analysis was the qualitative and quantitative comparison of neonatal symptomatic disease and long-term sequelae of congenitally CMV infected children born following maternal PI or NPI. Articles from MEDLINE and SCOPUS databases were systematically reviewed. Articles describing neonatal symptoms and/or long-term sequelae in infants and children with cCMV born to mothers following PI and NPI were eligible.From eligible articles, data on the prevalence of neonatal symptoms, sensorineural hearing loss (SNHL) or neurologic sequelae in children born following PI and NPI were extracted and statistically analyzed. Maternal infection status did not influence neonatal symptomatic disease (pooled Odds Ratio (OR) 0.83, 95 % CI [0.55; 1.27], p=0.397). Additionally, the two groups of cCMV infected children had similar risk of developing SNHL, bilateral SNHL or other neurologic outcomes. Importantly, these findings remained as such, when newborns identified through universal screening were separately analyzed. Finally, when data on symptomatic and/or asymptomatic newborns were evaluated alone, maternal type was not associated with outcomes examined. Considering available data, the universal screening of all newborns for CMV infection may be discussed as a perspective. The systematic review and meta-analysis were registered in PROSPERO (Prospero registration number: CRD42019125179).
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http://dx.doi.org/10.1016/j.jcv.2020.104518DOI Listing
August 2020

Facial necrotic ulcerative lesions in an adolescent female with granulomatosis with polyangiitis (GPA).

Clin Rheumatol 2020 Nov 1;39(11):3519-3520. Epub 2020 Jul 1.

Department of Pediatrics, Attikon General Hospital, National and Kapodistrian University of Athens, 1 Rimini Str., 124 62, Athens, Greece.

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http://dx.doi.org/10.1007/s10067-020-05264-4DOI Listing
November 2020

Low birth weight and head circumference as potential biomarkers of sensorineural hearing loss in asymptomatic congenitally CMV-infected infants.

J Clin Virol 2020 08 29;129:104471. Epub 2020 May 29.

Third Department of Pediatrics, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Background: Congenital cytomegalovirus infection (cCMV) represents the most common viral congenital infection and non-genetic cause of childhood sensorineural hearing loss (SNHL). Newborns with symptomatic cCMV disease are at high risk for long term neurologic sequalae. However, most newborns with cCMV are asymptomatic and have a significantly better prognosis. About 10 % may develop sequalae, mainly SNHL.

Objectives: This study aimed to evaluate risk factors associated with the development of sensorineural hearing loss, in children with asymptomatic congenital CMV infection.

Study Design: A total of 70 patients with asymptomatic cCMV were retrospectively evaluated. Maternal age, type and trimester of maternal infection, maternal or newborn treatment as well as gestational age and anthropometric measures of newborns were examined as predictors of SNHL.

Results: The incidence of SNHL in children with asymptomatic cCMV correlated with low birthweight as well as with both birth weight and head circumference low z-scores adjusted for gestational age. Logistic regression analysis confirmed these results. There was no association between type or trimester of maternal infection and the development of SNHL.

Discussion: Study results underscore the need for biomarkers to identify asymptomatic cCMV infants at risk for SNHL development, suggesting that z-scores of birth weight and head circumference adjusted for gestational age may be examined as such in larger cohorts.
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http://dx.doi.org/10.1016/j.jcv.2020.104471DOI Listing
August 2020

Faecal calprotectin: A useful biomarker in paediatric juvenile polyps.

J Paediatr Child Health 2020 11 20;56(11):1824-1826. Epub 2020 Apr 20.

Third Department of Paediatrics, "ATTIKON" University General Hospital, National and Kapodistrian University of Athens School of Health Sciences, Athens, Greece.

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http://dx.doi.org/10.1111/jpc.14888DOI Listing
November 2020

Mutations in Myosin 5B in Children With Early-onset Cholestasis.

J Pediatr Gastroenterol Nutr 2020 08;71(2):184-188

Paediatric Liver, GI & Nutrition Centre and MowatLabs.

Objectives: Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B.

Methods: Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease.

Results: Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3-92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 μmol/L (2-500), alanine aminotransferase 73I IU/L (32-114), γ-glutamyltransferase 7 IU/L (7-10), and serum bile acids 134 μmol/L (18-274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow-up was 5 years (2-22). At most recent follow-up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant.

Conclusions: We identified 6 patients, with mutations in MYO5B, early-onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.
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http://dx.doi.org/10.1097/MPG.0000000000002740DOI Listing
August 2020

Antenatal imaging and clinical outcome in congenital CMV infection: A field-wide systematic review and meta-analysis.

J Infect 2020 04 23;80(4):407-418. Epub 2020 Feb 23.

Third Department of Paediatrics, Attikon University General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens 115 27, Greece.

Objectives: Postnatal outcome in fetuses with congenital cytomegalovirus infection (cCMV) varies from asymptomatic infection to severe neurodevelopmental impairment. Αntenatal biomarkers of long-term clinical outcome, have yet to be established. Α systematic review and meta-analysis was performed to examine whether prenatal cerebral ultrasonography (US) and magnetic resonance imaging (MRI) findings in cCMV fetuses may predict clinical outcome.

Methods: PubMed and the Web of Science were systematically searched to identify studies reporting on any prenatal US and/or MRI imaging of fetuses with cCMV as well as their postnatal clinical outcome. All reported associations between imaging and postnatal clinical outcome were systematically extracted. Where appropriate, the reported associations were quantitatively synthesized within Bayesian random-effects meta-analyses.

Results: A total of 1336 studies were screened to identify 26 eligible observational studies. Overall, 4181 fetuses were studied, of which 1518 had been diagnosed with cCMV. All studies performed fetal US while in 14 (54%) MRI was also performed. Studies substantially varied in timing of fetal imaging, reporting of abnormalities, definition of poor outcome and statistical analysis. Among studies reporting on statistical significance, 6/6 for US and 3/4 for MRI identified significant associations between imaging findings and outcome. In our meta-analyses, within isolated abnormalities, only microcephaly had greater than 95% probability of being associated with poor outcome (OR 26.7; 95% CI, 1.44-1464.5; I, 19%). Effect sizes for US were higher than those for MRI findings.

Conclusions: Although studies displayed significant heterogeneity in both methodology and analytical decisions, it became evident that when both prenatal cerebral US and MRI are normal the negative predictive value of poor outcome is high. This is important for clinicians when consulting pregnant women. Need to standardize practices and definitions become evident.

Funding: There was no source of funding.
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http://dx.doi.org/10.1016/j.jinf.2020.02.012DOI Listing
April 2020

Length of stay, cost, and mortality of healthcare-acquired bloodstream infections in children and neonates: A systematic review and meta-analysis.

Infect Control Hosp Epidemiol 2020 03 3;41(3):342-354. Epub 2020 Jan 3.

Center for Clinical Epidemiology and Outcomes Research CLEO, Non-Profit Civil Partnership, Athens, Greece.

Objective: To estimate the attributable mortality, length of stay (LOS), and healthcare cost of pediatric and neonatal healthcare-acquired bloodstream infections (HA-BSIs).

Design: A systematic review and meta-analysis.

Methods: A systematic search (January 2000-September 2018) was conducted in PubMed, Cochrane, and CINAHL databases. Reference lists of selected articles were screened to identify additional studies. Case-control or cohort studies were eligible for inclusion when full text was available in English and data for at least 1 of the following criteria were provided: attributable or excess LOS, healthcare cost, or mortality rate due to HA-BSI. Study quality was evaluated using the Critical Appraisal Skills Programme Tool (CASP). Study selection and quality assessment were conducted by 2 independent researchers, and a third researcher was consulted to resolve any disagreements. Fixed- or random-effect models, as appropriate, were used to synthesize data. Heterogeneity and publication bias were evaluated.

Results: In total, 21 studies were included in the systematic review and 13 studies were included in the meta-analysis. Attributable mean LOS ranged between 4 and 27.8 days; healthcare cost ranged between $1,642.16 and $160,804 (2019 USD) per patient with HA-BSI; and mortality rate ranged between 1.43% and 24%. The pooled mean attributable hospital LOS was 16.91 days (95% confidence interval [CI], 13.70-20.11) and the pooled attributable mortality rate was 8% (95% CI, 6-9). A meta-analysis was not conducted for cost due to lack of eligible studies.

Conclusions: Pediatric HA-BSIs have a significant impact on mortality, LOS, and healthcare cost, further highlighting the need for implementation of HA-BSI prevention strategies.
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http://dx.doi.org/10.1017/ice.2019.353DOI Listing
March 2020

Rituximab as front-line treatment in refractory autoimmune hemolytic anemia.

Minerva Pediatr 2019 Nov 11. Epub 2019 Nov 11.

Third Department of Pediatrics, National and Kapodistrian University of Athens, General University Hospital "Attikon", Athens, Greece.

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http://dx.doi.org/10.23736/S0026-4946.19.05672-XDOI Listing
November 2019

Hypoprolactinemia as a Clue to Diagnosis of Mild Central Hypothyroidism due to Deficiency

J Clin Res Pediatr Endocrinol 2020 06 26;12(2):218-222. Epub 2019 Aug 26.

National and Kapodistrian University of Athens, “Attikon” University Hospital, Third Department of Pediatrics, Athens, Greece

Loss-of-function mutations of are an X-linked cause of central hypothyroidism (CeH) and hypoprolactinemia. A boy who is now 15.2 years old presented at the age of 7.69 years for evaluation of obesity. Previous thyroid function evaluation suggested CeH [FT4 0.6 ng/mL, thyroid-stimulating hormone (TSH) 2.2 mIU/L] but his physician took no action. At presentation he was clinically and biochemically euthyroid, prepubertal and obese. Serum prolactin (PRL) was undetectable. Biochemistry was normal except for mild hypercholesterolemia, total cholesterol 198 mg/dL. Subsequently FT4 and TSH levels fluctuated between 0.72-0.95 ng/dL (normal 0.8-2.0) and 1.94-5.77 mIU/L (normal 0.3-5.0), respectively. Sequencing of gene revealed a novel genetic change c.3805C>T in exon 19; substitution of amino acid Arginine at position 1269 with a premature «stop» codon resulting in an altered protein product. The patient additionally presented delayed adrenarche, low height velocity that resolved spontaneously and normal pubertal onset associated with increased FSH levels. At 14 years-of-age, while the patient was at Tanner stage 4, PRL levels became detectable, rising gradually to 2.3 ng/mL at last examination. Thyroxine replacement therapy resulted in decrease in total cholesterol 103 mg/dL. A high index of suspicion for the disorder is needed since several measurements of thyroid function may be required for CeH to be disclosed. The patient’s normal FT4 levels and normal intelligence would have resulted in a missed diagnosis if the serum PRL levels had not been measured. This case highlights the importance of measuring PRL in a boy with low normal FT4 and normal TSH levels.
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http://dx.doi.org/10.4274/jcrpe.galenos.2019.2019.0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291406PMC
June 2020

Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.

Arch Dis Child 2020 01 24;105(1):26-31. Epub 2019 Aug 24.

Amrita Institute of Medical Sciences, Kochi, India.

Objective: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).

Design: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns.

Setting: 39 NNUs from 12 countries.

Patients: Any neonate admitted to one of the participating NNUs.

Interventions: This was an observational cohort study.

Results: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%.

Conclusion: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.
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http://dx.doi.org/10.1136/archdischild-2019-316816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951234PMC
January 2020

Risk of congenital cytomegalovirus infection in children born to women with IgG avidity in the grey zone during first trimester of pregnancy.

J Matern Fetal Neonatal Med 2021 Jun 11;34(12):2025-2029. Epub 2019 Aug 11.

Fourth Department of Internal Medicine, General University Hospital "Attikon", National and Kapodistrian University of Athens, Athens, Greece.

Introduction: Cytomegalovirus (CMV) is the most common congenital viral infection and is regarded as the leading nongenetic cause of sensorineural hearing loss. Currently, international consensuses discourage prenatal screening of pregnant women. However, in few countries mainly in Southern Europe, screening of pregnant women for CMV infection is common practice. Management of women found with IgG+/IgM + and IgG avidity titers in the grey zone during first trimester causes significant stress to both families and health care workers.

Patients And Methods: Pregnant women referred to our outpatient clinic with the diagnosis of acute CMV infection (IgM+/IgG+) during early pregnancy (gestational age ≤ 14 weeks) and IgG avidity in the grey zone were prospectively followed. The administration of CMV-HIG was offered and follow-up included fetal U/S, amniocentesis for CMV-DNA detection and MRI when appropriate. All neonates were examined by urine PCR and prospectively followed according to existing recommendations.

Results: Ninety women (mean age 30.8 years) were retrospectively analyzed. Most (79.6%) received CMV-HIG. Four women terminated pregnancy (2 unrelated to CMV reasons and 2 because of CMV-positive amniotic fluid). Eighty-seven babies were born asymptomatic. Two newborns were diagnosed with congenital CMV infection. The overall transmission rate was 4.4%; 4.3 5.6% for those receiving or not CMV-HIG. No adverse outcomes were detected during follow-up (median 24 months). Maternal age, parity, detection of maternal CMV-viremia upon diagnosis, delay between diagnosis and consultation, gestational week of first consultation, administration of CMV-HIG and number of doses were not associated with the risk of vertical CMV transmission.

Discussions: Vertical transmission of CMV infection in pregnancies with acute CMV-infection and IgG avidity titers in the grey zone during first trimester was 4.4%, higher than that in infants born post nonprimary infection (NPI) during pregnancy. More powered studies are needed to prove a significant reduction in transmission using CMV-HIG.
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http://dx.doi.org/10.1080/14767058.2019.1651277DOI Listing
June 2021

Afebrile Kawasaki disease in infants.

Minerva Pediatr (Torino) 2021 Jun 2;73(3):283-285. Epub 2019 Jul 2.

Third Department of Pediatrics, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

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http://dx.doi.org/10.23736/S0026-4946.19.05589-0DOI Listing
June 2021