Navigating paediatric virology through the COVID­19 era (Review).

The present review article presents the key messages of the 8th Workshop on Paediatric Virology organised virtually by the Institute of Paediatric Virology based on the island of Euboea in Greece. The major topics covered during the workshop were the following: i) New advances in antiviral agents and vaccines against cytomegalovirus; ii) hantavirus nephropathy in children; iii) human rhinovirus infections in children requiring paediatric intensive care; iv) complications and management of human adenovirus infections; v) challenges of post­coronavirus disease 2019 (COVID­19) syndrome in children and adolescents; and vi) foetal magnetic resonance imaging in viral infections involving the central nervous system. The COVID­19 era requires a more intensive, strategic, global scientific effort in the clinic and in the laboratory, focusing on the diagnosis, management and prevention of viral infections in neonates and children.

Indications for magnetic resonance imaging of the fetal body (extra-central nervous system): recommendations from the European Society of Paediatric Radiology Fetal Task Force.

The indications for fetal body MRI are amplifying because of the expanding possibilities of fetal and perinatal therapy. However, huge heterogeneity regarding the indications for fetal body MRI is seen among different European countries that is mostly related to local use of US, but also to local fetal MRI expertise and legislation on pregnancy termination. The purpose of this article is to summarize the precise indications for fetal MRI, excluding the central nervous system. MRI indications arise from the sonographic findings, based on the operator's experience and the various practices in the countries and institutions represented on the European Society of Paediatric Radiology Fetal Task Force. We also highlight the strengths and weaknesses of fetal US and MRI of the fetal body.

The fetal brain: migration and gyration anomalies - pre- and postnatal correlations.

The cerebral cortex represents a laminar structure of precisely spatially organized neurons in horizontal layers and vertical columns. Neurogenesis, neuronal migration and neuronal wiring are tightly regulated and coordinated procedures that result in the accurate formation of the human cerebral cortex. Abnormal fetal corticogenesis results in several types of migration and gyration anomalies, known as malformations of cortical development, which have long been a topic of investigation. According to the stage of cortical development that is affected, with diverse genetic and non-genetic etiologies, these malformations can cause abnormal head size, abnormal brain surface and abnormal cortical layering with various degrees of neurodevelopmental delay and epilepsy. The pathogenesis of these malformations is multifactorial and includes genetic mutations or environmental insults, acquired either in utero at varying stages of brain development or during the perinatal period after corticogenesis. In this article, we focus on cortical malformations detected on fetal MRI. We present the main antenatal findings that should raise suspicion for malformations of cortical development, together with findings that might be missed on prenatal imaging and describe the correlations between fetal and postnatal MRI.

Profile of Volatile Compounds in Dessert Yogurts Prepared from Cow and Goat Milk, Using Different Starter Cultures and Probiotics.

The purpose of this study was to determine the profile of volatile compounds (aroma) and overall flavor in dessert yogurts prepared from cow and goat milk, using three different, commercially available starter cultures, in the presence or absence of probiotic bacteria and to correlate this to organoleptic evaluation results obtained using a consumer acceptability method. The extraction of volatile compounds was carried out by solid phase micro-extraction; separation and analysis by gas chromatography-mass spectrometry. Variations among the different classes of compounds (i.e., aldehydes, alcohols, ketones, volatile acids, hydrocarbons, and terpenes) were recorded for different treatments. The results showed that the main volatiles in the cow milk dessert yogurts without Bifidobacterium BB-12 were: acetaldehyde, 2,3-butanedione, 2,3-pentanedione, 3-OH-2-butanone, 2-propanone, hexanoic acid and limonene). Respective volatiles in cow milk dessert yogurts with Bifidobacterium BB-12 were: acetaldehyde, pentanal, hexanal, the same ketones, acetic acid and limonene). The volatiles in goat milk dessert yogurts without Lactobacillus acidophilus LA-5 were: acetaldehyde, the same ketones, no carboxylic acids, limonene, camphene, α- and ß-pinene. Respective volatiles in goat milk dessert yogurts with Lactobacillus acidophilus LA-5 were: aldehydes acetaldehyde, the same ketones, butanoic acid, α-pinene and camphene varying in concentration in different samples. Based on the results of volatiles and organoleptic evaluation, it can be concluded that dessert yogurts from cow milk without probiotic bacterial strains using the mild and classic starter cultures, and dessert yogurts from goat milk with probiotic bacterial strains using the classic and acidic starter cultures are found to be more organoleptically acceptable by consumers. In most cases, a positive correlation was found between dessert yogurt organoleptically determined flavor and volatiles (aldehydes, ketones and carboxylic acids).

The Cultural Adaptation of the Everyday Problems Test-Greek Version: An Instrument to Examine Everyday Functioning.

Assessing cognitive decline and everyday functioning (EvF) in older age is valuable in detecting age-related neurological disorders. In Greece, there is a lack of sensitive instruments that capture fluctuations in EvF among older persons who are cognitively healthy or have subtle cognitive impairments. The EPT 28-items test, a widely used paper-and-pencil EvF measure, was translated in Greek and adapted to the Greek culture in this study. A multi-step methodology using a sample of 139 older Greek persons was employed. The results indicate that the Greek version of the EPT 28-items (i.e., the EPT-G) was well adapted, representing everyday tasks in Greece within a good range of task difficulty. The psychometric properties of the EPT-G replicate those of the original instrument, capturing EvF fluctuations among older persons with mild cognitive impairments. It was concluded that the EPT-G is a useful measure of EvF among Greek older persons.

Indications for magnetic resonance imaging of the fetal central nervous system: recommendations from the European Society of Paediatric Radiology Fetal Task Force.

Fetal central nervous system MRI is a well-established method to complement a high-quality fetal ultrasound and to clarify sonographically detected abnormalities in complex pregnancies. However, there is still worldwide heterogeneity and confusion regarding the indications of fetal central nervous system MRI, which has roots in differences among countries regarding the performance of ultrasound examinations and legislation on pregnancy termination. The purpose of this article is to clarify the indications for fetal central nervous system MRI by focusing on the ultrasound findings that guide further investigation with MRI and highlight the strengths and the weaknesses of each modality on imaging the fetal central nervous system.

Update on current views and advances on RSV infection (Review).

Respiratory syncytial virus (RSV) infection represents an excellent paradigm of precision medicine in modern paediatrics and several clinical trials are currently performed in the prevention and management of RSV infection. A new taxonomic terminology for RSV was recently adopted, while the diagnostic and omics techniques have revealed new modalities in the early identification of RSV infections and for better understanding of the disease pathogenesis. Coordinated clinical and research efforts constitute an important step in limiting RSV global predominance, improving epidemiological surveillance, and advancing neonatal and paediatric care. This review article presents the key messages of the plenary lectures, oral presentations and posters of the '5th workshop on paediatric virology' (Sparta, Greece, 12th October 2019) organized by the Paediatric Virology Study Group, focusing on recent advances in the epidemiology, pathogenesis, diagnosis, prognosis, clinical management and prevention of RSV infection in childhood.

Transverse Vaginal Septum with a Hemiuterus: A Laparoscopic-Guided Abdominoperineal Approach.

BACKGROUND: Transverse vaginal septum is a rare Müllerian anomaly that can coexist with other defects. CASE: A 12-year-old patient was referred to our clinic for cyclic, lower abdominal pain. Magnetic resonance imaging revealed the presence of a transverse vaginal septum, a hemiuterus with a nonfunctioning rudimentary horn, and left unilateral ureter and kidney. The septum was excised laparoscopically assisted by a vaginal dilator to guide the dissection. The mucosal gap of the vagina was then bridged with sutures using the perineal approach. The postoperative course was uneventful and the patient was discharged with instructions for vaginal dilations. SUMMARY AND CONCLUSION: Early identification of a transverse vaginal septum and careful planning of the operation can improve the outcome of corrective surgery and prevent possible complications.

A paediatric influenza update 100 years after the Skyros island Spanish flu outbreak.

This year marks the 100th anniversary of the 1918 Spanish flu outbreak on the Greek Aegean Sea island of Skyros, which devastated its population in less than 30 days. According to Constantinos Faltaits's annals published in 1919, the influenza attack on the island of Skyros commenced acutely 'like a thunderbolt' on the 27th of October, 1918 and was exceptionally severe and fatal. At that time, the viral cause of the influenza had not been detected, while the total number of victims of the Spanish flu outbreak has been estimated to have surpassed 50 million, worldwide. Almost one century after this Aegean Sea island's tragedy, the '4th Workshop on Paediatric Virology', organised on the 22nd of September, 2018 in Athens, Greece, was dedicated to the 100 years of the 'Spanish' flu pandemic. This review article highlights the plenary and key lectures presented at the workshop on the recent advances on the epidemiology, clinical management and prevention of influenza in childhood.

Resolution of Hematocolpos in Adolescents Affected with Graft vs Host Disease.

BACKGROUND: Bone marrow transplantation is a lifesaving procedure for a range of serious benign or malignant hematological conditions. A proportion of patients, however, will develop graft vs host disease (GVHD), acute or chronic, with serious long-term sequalae. CASES: We present 2 cases of hematocolpos that developed in adolescence because of vaginal synechiae due to GVHD. The condition was initially asymptomatic, resolved spontaneously at first and recurred. In 1 girl blunt lysis of the adhesions was performed with the patient under general anesthesia, followed thereafter by local hydrocortisone and estriol treatment. SUMMARY AND CONCLUSION: Genital symptoms might not be readily reported by adolescents after bone marrow transplantation. Physicians should be aware of possible late effects of GVHD on genitalia, inquire about symptoms, and be acquainted with addressing complications, such as vaginal obstruction.

Paediatric Virology and its interaction between basic science and clinical practice (Review).

The 3rd Workshop on Paediatric Virology, which took place on October 7th, 2017 in Athens, Greece, highlighted the role of breast feeding in the prevention of viral infections during the first years of life. Moreover, it focused on the long-term outcomes of respiratory syncytial virus and rhinovirus infections in prematurely born infants and emphasised the necessity for the development of relevant preventative strategies. Other topics that were covered included the vaccination policy in relation to the migration crisis, mother­to­child transmission of hepatitis B and C viruses, vaccination against human papilloma viruses in boys and advances on intranasal live­attenuated vaccination against influenza. Emphasis was also given to the role of probiotics in the management of viral infections in childhood, the potential association between viral infections and the pathogenesis of asthma, fetal and neonatal brain imaging and the paediatric intensive care of children with central nervous system viral infections. Moreover, an interesting overview of the viral causes of perinatal mortality in ancient Greece was given, where recent archaeological findings from the Athenian Agora's bone well were presented. Finally, different continuing medical educational options in Paediatric Virology were analysed and evaluated. The present review provides an update of the key topics discussed during the workshop.

Paediatric Virology: A rapidly increasing educational challenge.

The '2nd Workshop on Paediatric Virology', which took place on Saturday the 8th of October 2016 in Athens, Greece, provided an overview on recent views and advances on Paediatric Virology. Emphasis was given to HIV-1 management in Greece, a country under continuous financial crisis, hepatitis B vaccination in Africa, treatment options for hepatitis C virus in childhood, Zika virus in pregnancy and infancy, the burden of influenza on childhood, hand-foot-mouth disease and myocarditis associated with Coxsackie viruses. Other general topics covered included a critical evaluation of Paediatric Accident and Emergency viral infections, multimodality imaging of viral infections in children, surgical approaches of otolaryngologists to complex viral infections, new advances in the diagnosis and treatment of viral conjunctivitis and novel molecular diagnostic methods for HPV in childhood. A brief historical overview of the anti-vaccination movement was also provided, as well as presentations on the educational challenge of Paediatric Virology as a new subspecialty of Paediatrics. This review highlights selected lectures and discussions of the workshop.

Bartonella henselae Infection: An Uncommon Mimicker of Autoimmune Disease.

We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata), chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256) against Bartonella confirmed the diagnosis of B. henselae infection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent.

Age-dependent changes in the size of adenotonsillar tissue in childhood: implications for sleep-disordered breathing.

OBJECTIVE: To analyze age-associated changes in linear and cross-sectional area (CSA) measurements of adenoid, tonsils, and pharyngeal lumen. STUDY DESIGN: Measurements were completed in head magnetic resonance imaging examinations performed for diagnostic purposes. Linear and nonlinear regression models were applied to describe the effect of age on the size of soft tissues and upper airway. RESULTS: Magnetic resonance imaging data were analyzed in 149 children without snoring (aged 0-15.9 years) and in 33 children with snoring (aged 1.6-15 years). In the children without snoring, adenoid size increased during the first 7-8 years of life and then decreased gradually [% (adenoid oblique width/mental spine-clivus length) = 11.38 + 1.52 (age) - 0.11 (age)(2), R(2) = 0.22, P < .01; adenoid CSA = 90.75 + 41.93 (age) - 2.47 (age)(2); R(2) = 0.50; P < .01]. Nasopharyngeal airway CSA increased slowly up to age 8 years and rapidly thereafter. Similar patterns were noted for the tonsils and oropharyngeal airway. In contrast, in children with snoring, adenoid and tonsils were large irrespective of age, and nasopharyngeal airway size increased slowly with age. CONCLUSIONS: In children without snoring, growing adenotonsillar tissue narrows the upper airway lumen to variable degrees only during the first 8 years of life. In contrast, in children with snoring, appreciable pharyngeal lymphoid tissue enlargement is present during the preschool years and persists beyond the eighth birthday.

Malrotation of the intestine and chronic volvulus as a cause of protein-losing enteropathy in infancy.

Protein-losing enteropathy in children is caused by intestinal metabolic, inflammatory, or infectious processes, or by lymphatic obstruction (intestinal lymphangiectasia). In this report, a 17-month-old child is presented with protein-losing enteropathy due to intestinal malrotation and chronic midgut volvulus causing lymphatic obstruction and spillage of lymph in the intestine and the peritoneum. This report should alert the pediatrician that intestinal malrotation should be added to the wide list of possible causes of protein-losing enteropathy in children.

Magnetic resonance imaging visualization of a vaginal septum.

Magnetic resonance imaging is considered the gold-standard imaging technique in cases of Müllerian and vaginal anomalies, however, vaginal delineation often proves difficult, owing to the fact that vaginal walls are normally collapsed and in close proximity. Instilling gel through the introitus allows for better depiction of the distal vagina.

Haemostatic profile of healthy premature small for gestational age neonates.

BACKGROUND: The pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood. OBJECTIVE: To evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration. STUDY DESIGN: We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) <37 weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, von Willebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters. RESULTS: Premature SGA infants presented significantly lower levels of fibrinogen (p<0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p<0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters. CONCLUSIONS: Despite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms.

Elevated markers of thrombin generation and fibrinolysis in patients with active and quiescent ulcerative colitis.

BACKGROUND: Prothrombotic abnormalities within the coagulation system, the presence of microvascular thrombi in intestinal mucosa, and the increased risk of thromboembolic complications in patients with Inflammatory bowel disease, suggest that a hypercoagulable state may be an important contributing factor in disease pathogenesis. The activation of the coagulation system in a cohort of ulcerative colitis patients was investigated. MATERIAL/METHODS: Markers of coagulation activation in blood (thrombin-antithrombin complex, TAT; prothrombin fragments 1 and 2, F1+2; and D-dimers) and markers of inflammation (erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; and fibrinogen) were measured in 38 patients with active and 13 patients with long-standing quiescent ulcerative colitis. Disease activity was assessed by clinical, endoscopic, and histological criteria. The markers of coagulation activation were also measured in 28 healthy volunteers. RESULTS: There were no differences in TAT, F1+2, and D-dimer plasma levels between active and inactive ulcerative colitis. D-dimer and F1+2 levels were significantly higher in the active ulcerative colitis patients than in the healthy controls. Plasma levels of TAT, F1+2, and D-dimers did not differ between inactive ulcerative colitis patients and healthy controls. However, both active and inactive ulcerative colitis patients had significantly higher proportions of elevated (above-normal) values of coagulation markers than the healthy controls. Correlation analyses revealed strong correlation between ESR, fibrinogen, and D-dimers, which also correlated with the severity and extent of ulcerative colitis. CONCLUSIONS: A chronic low-grade activation of coagulation exists in ulcerative colitis, regardless of disease activity, and it might be implicated in disease pathogenesis.