Blood Adhesion Molecules as Biomarkers in Children with Chronic Urticaria.

BACKGROUND: The prevailing etiological model of both acute and chronic urticaria implicates specific allergen exposure that triggers the local release of vasoactive factors and inflammatory adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), P-selectin and E-selectin in the superficial dermis. This study focused on the possible role of VCAM-1 and ICAM-1 as biomarkers in children with acute and chronic urticaria. METHODS: This study involved 184 children, 40 with acute urticaria, 71 with chronic urticaria, and 73 matched comparison subjects. The serum levels of ICAM-1 and VCAM-1 were determined in venous blood in all the participants on enrollment. Antihistamine treatment was administered to all the patients. In the children with chronic urticaria, the Urticaria Activity Score Questionnaire (UAS7) was completed daily by the parents. In 16 of the patients with acute urticaria and 43 with chronic urticaria, the serum levels of ICAM-1 and VCAM-1 were determined at follow-up after 6-8 weeks of treatment. RESULTS: The mean serum levels of both VCAM-1 and ICAM-1 were higher in both groups of children with urticaria than in the comparison subjects at the start of the study. In the chronic urticaria group, the levels decreased significantly (p = 0.03 and p = 0.01, respectively) following treatment. Similarly, the acute urticaria group exhibited significant reduction in the mean levels of VCAM and ICAM (p < 0.001). In both groups, the mean level of ICAM after treatment was comparable with that of the comparison group. CONCLUSIONS: VCAM-1 and ICAM-1 are suggested as promising biomarkers for monitoring both acute and chronic urticaria in children. Future research should explore their utility in larger cohorts and investigate their role in personalized treatment strategies.

A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta-analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using random-effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower-middle, 12 in upper-middle, and only two in high-income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta-analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta-analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high-income countries.

Ιnterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation.

Childhood asthma is a chronic inflammatory airway disorder that can drive tissue remodeling. Neutrophils are amongst the most prominent inflammatory cells contributing to disease manifestations and may exert a potent role in the progression of inflammation to fibrosis. However, their role in asthma exacerbation is still understudied. Here, we investigate the association between neutrophil extracellular traps (NETs) and lung fibroblasts in childhood asthma pathophysiology using serum samples from pediatric patients during asthma exacerbation. Cell-based assays and NETs/human fetal lung fibroblast co-cultures were deployed. Increased levels of NETs and interleukin (IL)-17A were detected in the sera of children during asthma exacerbation. The in vitro stimulation of control neutrophils using the sera from pediatric patients during asthma exacerbation resulted in IL-17A-enriched NET formation. The subsequent co-incubation of lung fibroblasts with in vitro-generated IL-17A-enriched NETs led fibroblasts to acquire a pre-fibrotic phenotype, as assessed via enhanced CCN2 expression, migratory/healing capacity, and collagen release. These data uncover the important pathogenic role of the NET/IL-17A axis in asthma exacerbation, linking lung inflammation to fibroblast dysfunction and fibrosis.

Vaccination programs for children aged up to 18 years in Europe, 2020.

Although all European countries have vaccination policies for children, there are no comprehensive studies of pediatric vaccination programs in Europe. We studied vaccination programs for children in Europe. Vaccinations against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, hepatitis B, measles, mumps, rubella, and influenza existed in 42 countries, against human papilloma virus in 41 countries, and against pneumococcus in 40 countries. In addition, the following vaccinations existed: against tuberculosis (35 countries), hepatitis A (33), meningococcus A, C, W, Y (30), rotavirus and varicella (28 countries each), meningococcus B (24), tick-born encephalitis (22), and meningococcus C (16). Mandatory vaccinations are implemented in 21 countries, mainly against diphtheria, tetanus, pertussis, poliomyelitis, H. influenzae type b, hepatitis B, measles, mumps, rubella, tuberculosis, and pneumococcus. There are significant differences among pediatric vaccination programs in Europe regarding number, schedules, indications, and regulatory frame (recommended or mandatory vaccinations). A consensus-based vaccination program for all children is needed.

Drug allergy evaluation in children with suspected mild antibiotic allergy.

Background: Adverse antibiotic reactions caused by an immunological mechanism are known as allergic reactions. The percentage of reported antibiotic allergies is likely to differ from the one validated after a drug provocation test (DPT) with the culprit antibiotic. This study aimed to compare the percentage of children who were thought to be allergic to a certain antibiotic with those who have a true allergy, as confirmed by DPTs. We also validated Skin Prick Tests (SPTs) and Intradermal Tests (IDTs) by assessing their sensitivity and specificity, in diagnosing antibiotic allergies using DPT as the gold standard. Furthermore, we investigated epidemiological risk factors such as personal and family history of atopic disease and eosinophilia. Methods: Children with a history of possible allergic reaction to an antibiotic underwent a diagnostic procedure that included: (1) Eosinophil blood count, (2) SPTs, (3) IDTs and (4) DPTs. The parameters were compared with Pearson's Chi-Square and Fisher's Exact Test. Several risk factors that were found significant in univariate analysis, such as personal and family history of atopic disease, and positive SPTs and IDTs were examined with multiple logistic regression analysis to see if they were related to a higher risk for a positive DPT. Results: Semi-synthetic penicillin was the most common group of antibiotics thought to cause allergic reactions in this study. Overall, 123 children with a personal history of an adverse reaction to a certain antibiotic, were evaluated. In 87.8% of the cases, the symptoms had occurred several hours after administration of the culprit antibiotic. Both SPTs and IDTs had low sensitivity but high specificity. Moreover, they had a high positive predictive value (PPV). In contrast, eosinophilia was not recognized as a risk factor. Seventeen patients (13.8%) had a true antibiotic allergy, as confirmed by a positive DPT. A positive IDT was a strong predictor of a positive DPT, along with a positive personal and family history of atopy. Conclusion: SPTs and IDTs are very reliable in confirming antibiotic allergy when found positive. A negative result of a SPT highly predicts a negative DPT. A positive IDT and a positive personal and family history of atopy were recognized as significant risk factors for antibiotic allergy.

Legionella pneumophila: The Journey from the Environment to the Blood.

An outbreak of a potentially fatal form of pneumonia in 1976 and in the annual convention of the American Legion was the first time that Legionella spp. was identified. Thereafter, the term Legionnaires' disease (LD) was established. The infection in humans is transmitted by the inhalation of aerosols that contain the microorganisms that belong to the Legionellaceae family and the genus Legionella. The genus Legionella contains genetically heterogeneous species and serogroups. The Legionella pneumophila serogroup 1 (Lp1) is the most often detected strain in outbreaks of LD. The pathogenesis of LD infection initiates with the attachment of the bacterial cells to the host cells, and subsequent intracellular replication. Following invasion, Legionella spp. activates its virulence mechanisms: generation of specific compartments of Legionella-containing vacuole (LCV), and expression of genes that encode a type IV secretion system (T4SS) for the translocation of proteins. The ability of L. pneumophila to transmigrate across the lung's epithelium barrier leads to bacteremia, spread, and invasion of many organs with subsequent manifestations, complications, and septic shock. The clinical manifestations of LD depend on the bacterial load in the aerosol, the virulence factors, and the immune status of the patient. The infection has two distinct forms: the non- pneumatic form or Pontiac fever, which is a milder febrile flu-like illness, and LD, a more severe form, which includes pneumonia. In addition, the extrapulmonary involvement of LD can include heart, brain, abdomen, and joints.

Management of antibiotic allergy in children: a practical approach.

BACKGROUND: About 10% of children are declared as allergic to antibiotics, with beta(ß)-lactams being the most common perpetrators. However, few of these are confirmed by allergy tests. This characteristic of being allergic follows a child well into adulthood, leading to alternative, usually more expensive broad-spectrum antibiotics, contributing to antibiotic resistance and increasing healthcare expenses. OBJECTIVE: This review presents a practical approach to managing pediatric patients with antibiotic hypersensitivity reactions. MATERIAL AND METHODS: We updated the guidelines on antibiotic allergy in children by conducting systematic literature research using the best available evidence from PubMed search by entering the keywords "antibiotic allergy" and "children." The search output yielded 5165 citations. RESULTS: Management of antibiotic allergy depends on the culprit antibiotic, and it includes confirmation of the diagnosis and finding a safe alternative to the culprit antibiotic. In particular patients with a history indicative of penicillin allergy can be treated with cephalosporins as an alternative to penicillin, especially with third-generation cephalosporins, except for those with similar R1 side chains. In patients with a history of immediate-type reactions to cephalosporins who require treatment with cephalosporins or penicillin, skin tests with cephalosporin or penicillin with different side chains should be performed. If allergy to macrolides is suspected, challenge tests are currently the only reliable diagnostic tool. The best strategy for managing patients with sulfonamide hypersensitivity is an alternative antibiotic. The skin prick tests and intradermal tests are not recommended for diagnosis of quinolone allergy, as they can activate dermal mast cells leading to false-positive results. Quinolone challenge test is the most appropriate test for diagnosing quinolone hypersensitivity. CONCLUSION: Although adverse drug reactions to antibiotics are frequently documented, immunologically mediated hypersensitivity is unusual. In the event of an reaction, an appropriate diagnostic workup is required to identify the drug's causal role. It is critical to avoid "labeling" a child as allergic without first conducting a proper diagnostic workup.

Management of antibiotic allergy in children: a practical approach

Background: About 10% of children are declared as allergic to antibiotics, with beta(β)-lactams being the most common perpetrators. However, few of these are confirmed by allergy tests. This characteristic of being allergic follows a child well into adulthood, leading to alternative, usually more expensive broad-spectrum antibiotics, contributing to antibiotic resistance and increasing healthcare expenses.Objective: This review presents a practical approach to managing pediatric patients with antibiotic hypersensitivity reactions.Material and methods: We updated the guidelines on antibiotic allergy in children by conducting systematic literature research using the best available evidence from PubMed search by entering the keywords “antibiotic allergy” and “children.” The search output yielded 5165 citations.Results: Management of antibiotic allergy depends on the culprit antibiotic, and it includes confirmation of the diagnosis and finding a safe alternative to the culprit antibiotic. In particular patients with a history indicative of penicillin allergy can be treated with cephalosporins as an alternative to penicillin, especially with third-generation cephalosporins, except for those with similar R1 side chains. In patients with a history of immediate-type reactions to cephalosporins who require treatment with cephalosporins or penicillin, skin tests with cephalosporin or penicillin with different side chains should be performed. If allergy to macrolides is suspected, challenge tests are currently the only reliable diagnostic tool. The best strategy for managing patients with sulfonamide hypersensitivity is an alternative antibiotic. The skin prick tests and intradermal tests are not recommended for diagnosis of quinolone allergy, as they can activate dermal mast cells leading to false-positive results. Quinolone challenge test is the most appropriate test for diagnosing quinolone hypersensitivity (AU)

Views and Attitudes of Blood Donors toward Blood Donation during the COVID-19 Pandemic in Thrace Region, Greece.

The COVID-19 pandemic has been going on for the last two years and it has affected our society and, amongst other things, has had a negative impact on blood donation, which has led to a significant reduction in blood supplies worldwide. The imposed restrictions in terms of physical presence and transportation, and the fear of the unknown, have aggravated the situation. In Greece, after the first cases of COVID-19 were reported, the blood supplies at the blood transfusion units (BTUs) were dramatically reduced. Although the blood transfusions were lessened during the COVID-19 pandemic period, the blood stocks at all the BTUs of the country were also reduced.

Prevalence of anti-SARS-CoV-2 IgG antibodies in a group of patients, a control group, and healthcare workers of Thrace area in Greece, by the use of two distinct methods.

INTRODUCTION: The aim of this study was to assess the clinical performance of different automated immunoassays available in Europe to detect anti-SARS-CoV-2 antibodies; an ELISA assay and a CLIA. The second goal was to estimate the seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Evros area during the first pandemic wave of COVID-19. METHODS: The study included serum samples from 101 patients with confirmed COVID-19 by RT-PCR and 208 negative patients. Furthermore, it included 1036 healthcare workers (HWs) of the Evros Region, Northern Greece. The measurement of anti-SARS-CoV-2 antibodies was performed using the Abbott SARS-CoV-2 IgG and anti-SARS-CoV-2 ELISA IgG assay (Epitope Diagnostics, USA). RESULTS: Of 101 confirmed COVID-19 patients, 82 were hospitalized and 19 were outpatients. Hospitalized patients had higher IgG levels in comparison to outpatients (6.46±2.2 vs. 3.52±1.52, p<0.001). Of 208 non-COVID-19 patients only 1 was positive in both ELISA and CLIA assay. SARS-CoV-2-IgG antibodies were detected in 6 HWs out of 1036 (0.58%) with mean S/CO-value of anti-SARS-CoV-2 IgG 3.12±1.3 (confidence interval 0.95), which was lower than in COVID-19 patients (3.12 vs. 5.9; p=0.016). The clinical evaluation of two immunoassays showed remarkably high true positivity rates in the confirmed COVID-19 patients. Sensitivities obtained with CLIA and ELISA methods were 99.02% vs. 97.09% and specificities 99.52% vs 99.05% respectively. CONCLUSIONS: We found an acceptable accordance between CLIA and ELISA assays in the confirmed COVID-19 patients. In all subjects included in this study in the past medical history, the information that was obtained included details about the presence of autoimmune diseases.

Influence of education and residence on the parental search for pediatric surgical information on the internet.

BACKGROUND: The internet is a valuable tool for access to health-related information. There is limited literature regarding its use by parents of children with surgical conditions. AIM: To investigate internet usage by parents seeking information about the surgical conditions of their offspring in relation to epidemiological factors such as family residential area and parental educational level and to subsequently review the literature regarding this topic. METHODS: An anonymous questionnaire about internet usage was completed by eligible parents of children who were admitted to our clinic for minor surgical procedures during a six-month period. RESULTS: Our results demonstrated that the internet has been mostly used by mothers for children's health information. Google was the most commonly used search engine, while pediatricians were the first parental choice for 'live' information. Only one-quarter of the parents informed their doctor about the information found online. Nine of ten parents had a positive opinion of an official website managed by the doctors of our clinic. Our results mostly agreed with the international literature. CONCLUSION: In conclusion, the establishment of official websites (designed and managed by specialists) that parents can access to receive appropriate health information is mandatory in the internet era.

Parents under siege: the psychological impact of COVID-19 outbreak on children's caregivers.

AIMS OF THE STUDY: It is well known that parenting stress is an important but often underestimated psychosocial variable. Data regarding the impact of the corona virus disease 2019 (COVID-19) outbreak on parental psychology are currently lacking. The aim of the present study was to assess parenting stress during the COVID-19 pandemic in Greece. METHODS: An Internet e-survey was conducted adhering to CHERRIES guidelines of the EQUATOR network and released from 16 March to 22 March 2020, using the Perceived Stress Scale (PSS) and Revised Impact of Event Scale (IES-R). A convenience sample of 1105 Greek parents of children with or without chronic or severe underlying disorders was enrolled, identified by a network of collaborating paediatricians across the country, and invited via personal emails. RESULTS: The participation rate was 91.6% and the completion rate was 100%. A total of 178 (16.1%) of the participants had children with underlying disorders (198 affected children in total). Parents of children with underlying disorders had significantly higher stress levels than those of healthy children (PSS 21.22 ± 5.06 vs 19.02 ± 6.85, p <0.001; IES-R 40.71 ± 11.58 v. 35.86 ± 12.69, p <0.001), particularly those caring for children with cardiovascular or respiratory disorders, or immunodeficiencies. The presence of children with underlying disorders was a strong predictor of PSS and IES-R scores, independently of parental sex, age, education and place of residence. CONCLUSIONS: The impact of COVID-19 outbreak on parental stress is substantial, and those caring for children with underlying disorders are more profoundly affected. Pending the global socioeconomic rebooting after the pandemic, the possible short- and long-term consequences of parental stress should not be ignored. As for other vulnerable groups, accurate health information and resources for psychological support should be provided to parents, especially those caring for children with underlying disorders.

Vaccination programs for pregnant women in Europe, 2021.

Vaccination during pregnancy is increasingly adopted worldwide in order to protect the mother and her offspring. We studied the current vaccination programs specifically for pregnant women in 42 European countries. Vaccination programs for pregnant women are in place in 37 countries, as follows: influenza (36 countries), pertussis (28), hepatitis B (12), tetanus (10), pneumococcal disease (10), meningococcal disease (10), rabies (8), tick-borne encephalitis (6), hepatitis A (5), poliomyelitis (4), diphtheria (3), Haemophilus influenzae (2), and human papilloma virus (1). Recommendations for vaccination against influenza and pertussis concern almost exclusively pregnant women regardless of high-risk conditions, however differences between vaccination recommendations are noted in terms of timing. Vaccinations against hepatitis B, hepatitis A, pneumococcal disease, meningococcal disease, poliomyelitis, H. influenzae, rabies, and tick-born encephalitis mainly concern pregnant women at high-risk for exposure or serious illness and post-exposure vaccinations. Overall, five European countries have no vaccination recommendations specifically for pregnant women. In conclusion, there are significant differences in vaccination programs for pregnant women in Europe. Vaccination programs for pregnant women should expand in order to protect maternal and infant health. A consensus-based vaccination program is needed.

Levels of Produced Antibodies after Vaccination with mRNA Vaccine; Effect of Previous Infection with SARS-CoV-2.

The aim of this study was to estimate the immunogenic effect of mRNA vaccine against SARS-CoV-2. This study included 510 participants who received mRNA vaccine. The measurement of anti-COVID-19 antibodies was performed using the Abbott SARS-CoV-2 IgG quantitative assay (Abbott). Overall, mean titer of anti-Spike antibodies was 19,319.2 ± 1787.5 AU/mL. Vaccination induced a robust immunogenic response in those previously infected with SARS-CoV-2 compared with non-infected subjects. Additionally, individuals that were asymptomatic after vaccination produced lower levels of antibodies compared to feverish individuals. In conclusion, remarkably high levels of anti-Spike COVID-19 antibodies were observed after vaccination.

Tacrolimus Immunosuppression Causes Drug-Induced Hypersensitivity Reactions in Liver-Transplant Patients: A 3-Case Report.

BACKGROUND: Drug-induced hypersensitivity reactions attributed to the immunosuppressive agent tacrolimus after an organ transplant are rare in the literature. We present 3 cases of male adult patients grafted with a cadaveric liver who developed delayed hypersensitivity reactions to tacrolimus in the form of the prolonged-release capsules (Advagraf). Furthermore, the appropriate drug concentration solutions used for allergy testing are proposed. METHODS: All patients received a liver transplant (LT) because of cirrhosis of various etiologies. They were immunosuppressed with tacrolimus once daily. Several months after they had been placed on an immunosuppressive regimen with tacrolimus in the form of prolonged-release capsules (Advagraf), the patients presented with delayed hypersensitivity reactions and torturous pruritic rash that affected the whole body and was unresponsive to treatment with oral ursodeoxycholic acid, cholestyramine, or levocetirizine. Allergy testing that was performed by skin prick testing was negative. Nevertheless, intradermal testing yielded positive results in all 3 patients. Management was by interruption of the culprit agent, which was followed by symptom resolution. The immunosuppressive treatment was continued with alternative drugs. RESULTS: Appropriate nonirritating drug concentration solutions of the drug used for intradermal testing were highly sensitive and confirmed the clinical diagnosis of tacrolimus allergy in all the affected patients. CONCLUSION: Immunosuppressive treatment with tacrolimus in the form of prolonged-release capsules may cause a drug hypersensitivity reaction. A suspicion of allergy warrants a referral for allergy testing. Pruritic rash refractory to treatment in liver transplanted patients should be evaluated by an allergist for possible drug allergy when bile stasis and graft disease have been excluded. Intradermal testing has proven a highly sensitive method for confirming a drug allergy diagnosis, whereas skin prick testing did not.

The prevalence of HCV RNA positivity in anti-HCV antibodies-negative hemodialysis patients in Thrace Region. Multicentral study.

INTRODUCTION: HCV infection in patients under hemodialysis for end stage chronic kidney disease (ESCKD) may exist despite the absence of anti-HCV antibodies. Molecular methods are widely accepted as "gold standard" techniques for the detection of viral RNA. However, the molecular methods are more expensive in comparison to conventional methods and their replacement is not cost-effective. The aim of this study was to estimate the prevalence of HCV RNA positivity in anti-HCV negative hemodialysis patients and evaluate new diagnostic methods for the detection and the monitoring of hepatitis C in ESCKD patients. METHODS: The study was performed in four hospitals of Thrace region of Greece and 233 patients with no history of hepatitis C were enrolled. Measurement of anti-HCV antibodies and HCV core antigen was performed by microparticle chemiluminescence immunoassay. Molecular detection of viral RNA was performed by the real-time RT PCR. RESULTS: The mean age of the patients was 64.9 ± 23.3 years. HCV-Ag was positive in 2/233 patients (0.86%). Nevertheless, viral RNA was negative in those patients. CONCLUSIONS: The results of the present study showed that the incidence of HCV-RNA in patients with negative anti-HCV Abs, in hemodialysis patients in Thrace region of Greece was negligible (0/233).

Subjective sleep-related breathing disorders and executive function in children with intermittent or mild persistent asthma.

OBJECTIVE: The impact on executive function performance of sleep-related disorders in asthmatic children has been scarcely studied in community settings. The aims of the present study were to assess the prevalence of sleep-related breathing disorders (SRBD) in children with intermittent or mild persistent asthma in primary care settings, and to examine the possible correlations with measures of executive function. METHODS: We performed a case-control study including 76 children with asthma (intermittent or mild persistent) and 85 healthy controls. The parents of both patients and controls completed the Paediatric Seep Questionnaire (PSQ) and the Behaviour Rating Inventory of Executive Function (BRIEF) questionnaire. RESULTS: We did not find any statistically significant differences regarding the scales of PSQ. Additionally, there were no statistical differences between asthmatic children and controls regarding the scales of the BRIEF questionnaire. In both asthmatic children and controls the score of the scale of obstructive sleep-related breathing disorder was significantly correlated with the T scores of the two composite scales (BRI and MI) and the Global Executive Composite. CONCLUSION: In children with intermittent or mild persistent asthma under the care of private general paediatricians there were no statistically significant differences regarding subjective SBD compared to the healthy controls. Also there were no statistical differences between asthmatic children and controls regarding behavioural correlates of executive function during everyday life.