Assessment of Medical Test Overuse and Its Impact on Pediatric Emergency Department Outcomes in Upper Respiratory Tract Infections in a University Hospital in Lithuania.

Medical overuse poses potential risks to patients and contributes to increasing healthcare costs, pediatric emergency departments (PED) in particular. Often, upper respiratory tract infection (URTI) cases are viral-induced and self-limiting, and they do not require specific investigations or treatment. We conducted a retrospective study from 1 December 2021 to 31 January 2022, thereby aiming to identify the common tests and factors influencing specific diagnostic and treatment decisions for URTI in PED. In total, 307 (74.9%) URTI cases underwent complete blood count (CBC) tests, 312 (76.1%) were subjected to C-reactive protein (CRP) tests, and 110 (26.8%) received urinalysis tests. Patients with a longer duration of fever and a physician's suspicion of bacterial infection were more likely to receive CBC, CRP, and/or urinalysis tests (p < 0.05). Moreover, 75.1% of the cases were classified as viral URTIs, 9.8% were bacterial URTIs, and 15.1% were unspecified. Notably, 86 (20.1%) children received antibiotics and antibiotic prescription correlated with age, tonsillitis diagnosis, CRP values higher than 30 mg/L, and a CBC of p < 0.05. Patients triaged in the second or third categories were three times more likely to be observed for 24 h compared to patients with URTI and the fourth triage category (p < 0.05). This study highlights the need for interventions to improve the appropriateness of emergency service utilization, thereby emphasizing the importance of judicious decision making in managing pediatric URTIs.

Over-investigation and overtreatment in pediatrics: a survey from the European Academy of Paediatrics and Japan Pediatric Society.

Introduction: Avoiding over-investigation and overtreatment in health care is a challenge for clinicians across the world, prompting the international Choosing Wisely campaign. Lists of recommendations regarding medical overactivity are helpful tools to guide clinicians and quality improvement initiatives. We aimed to identify the most frequent and important clinical challenges related to pediatric medical overactivity in Europe and Japan. Based on the results, we aim to establish a (European) list of Choosing Wisely recommendations. Methods: In an online survey, clinicians responsible for child health care in Europe and Japan were invited to rate 18 predefined examples of medical overactivity. This list was compiled by a specific strategic advisory group belonging to the European Academy of Paediatrics (EAP). Participants were asked to rate on a Likert scale (5 as the most frequent/important) according to how frequent these examples were in their working environment, and how important they were considered for change in practice. Results: Of 2,716 physicians who completed the survey, 93% (n = 2,524) came from 17 countries, Japan (n = 549) being the largest contributor. Pediatricians or pediatric residents comprised 89%, and 51% had 10-30 years of clinical experience. Cough and cold medicines, and inhaled drugs in bronchiolitis were ranked as the most frequent (3.18 and 3.07 on the Likert scale, respectively), followed by intravenous antibiotics for a predefined duration (3.01), antibiotics in uncomplicated acute otitis media (2.96) and in well-appearing newborns. Regarding importance, the above-mentioned five topics in addition to two other examples of antibiotic overtreatment were among the top 10. Also, IgE tests for food allergies without relevant medical history and acid blockers for infant GER were ranked high. Conclusion: Overtreatment with antibiotics together with cough/cold medicines and inhaled drugs in bronchiolitis were rated as the most frequent and important examples of overtreatment across countries in Europe and Japan.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Exploring Non-Invasive Salivary Biomarkers for Acute Pain Diagnostics: A Comprehensive Review.

Pain is one of the most common complaints leading to a pediatric emergency department visit and is associated with various painful procedures, leading to increased anxiety and stress. Assessing and treating pain in children can be challenging, so it is crucial to investigate new methods for pain diagnosis. The review aims to summarize the literature on non-invasive salivary biomarkers, such as proteins and hormones, for pain assessment in urgent pediatric care settings. Eligible studies were those that included novel protein and hormone biomarkers in acute pain diagnostics and were not older than 10 years. Chronic pain studies were excluded. Further, articles were divided into two groups: studies in adults and studies in children (<18 years). The following characteristics were extracted and summarized: study author, enrollment date, study location, patient age, study type, number of cases and groups, as well as tested biomarkers. Salivary biomarkers, such as cortisol, salivary α-amylase, and immunoglobulins, among others, could be appropriate for children as saliva collection is painless. However, hormonal levels can differ among children in different developmental stages and with various health conditions, with no predetermined levels of saliva. Thus, further exploration of biomarkers in pain diagnostics is still necessary.

Platelet role in the prediction of MIS-C severity.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) has been reported as one of the cytokine storm syndromes associated with COVID-19. Despite the several proposed diagnostic criteria, MIS-C remains a diagnostic and clinical challenge. Recent studies have demonstrated that platelets (PLTs) play a crucial role in COVID-19 infection and its prognosis. This study aimed to investigate the clinical importance of PLT count and PLT indices in predicting MIS-C severity in children. Patients and methods: We conducted a retrospective single-center study at our university hospital. A total of 43 patients diagnosed with MIS-C during a 2-year period (from October 2020 to October 2022) were included in the study. MIS-C severity was evaluated according to the composite severity score. Results: Half of the patients were treated in the pediatric intensive care unit. No single clinical sign was associated with a severe condition, except for shock (p = 0.041). All the routine biomarkers, such as complete blood count (CBC) and C-reactive protein (CRP), used for MIS-C diagnosis were significant in predicting MIS-C severity. Single PLT parameters, such as mean PLT volume, plateletcrit, or PLT distribution width, did not differ between the severity groups. However, we found that a combination of PLT count and the previously mentioned PLT indices had the potential to predict MIS-C severity. Conclusions: Our study emphasizes the importance of PLT in MIS-C pathogenesis and severity. It revealed that together with routine biomarkers (e.g., CBC and CRP), it could highly improve the prediction of MIS-C severity.

Induced pain affects auricular and body biosignals: From cold stressor to deep breathing.

Pain affects every fifth adult worldwide and is a significant health problem. From a physiological perspective, pain is a protective reaction that restricts physical functions and causes responses in physiological systems. These responses are accessible for evaluation via recorded biosignals and can be favorably used as feedback in active pain therapy via auricular vagus nerve stimulation (aVNS). The aim of this study is to assess the significance of diverse parameters of biosignals with respect to their deflection from cold stressor to deep breathing and their suitability for use as biofeedback in aVNS stimulator. Seventy-eight volunteers participated in two cold pressors and one deep breathing test. Three targeted physiological parameters (RR interval of electrocardiogram, cardiac deflection magnitude Z AC of ear impedance signal, and cardiac deflection magnitude PPG AC of finger photoplethysmogram) and two reference parameters (systolic and diastolic blood pressures BP S and BP D) were derived and monitored. The results show that the cold water decreases the medians of targeted parameters (by 5.6, 9.3%, and 8.0% of RR, Z AC, and PPG AC, respectively) and increases the medians of reference parameters (by 7.1% and 6.1% of BP S and BP D, respectively), with opposite changes in deep breathing. Increasing pain level from relatively mild to moderate/strong with cold stressor varies the medians of targeted and reference parameters in the range from 0.5% to 6.0% (e.g., 2.9% for RR, Z AC and 6.0% for BP D). The physiological footprints of painful cold stressor and relaxing deep breathing were shown for auricular and non-auricular biosignals. The investigated targeted parameters can be used as biofeedback to close the loop in aVNS to personalize the pain therapy and increase its compliance.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

Digital child health: opportunities and obstacles. A joint statement of European Academy of Paediatrics and European Confederation of Primary Care Paediatricians.

The advancement of technology and the increasing digitisation of healthcare systems have opened new opportunities to transform the delivery of child health services. The importance of interoperable electronic health data in enhancing healthcare systems and improving child health care is evident. Interoperability ensures seamless data exchange and communication among healthcare entities, providers, institutions, household and systems. Using standardised data formats, coding systems, and terminologies is crucial in achieving interoperability and overcoming the barriers of different systems, formats, and locations. Paediatricians and other child health stakeholders can effectively address data structure, coding, and terminology inconsistencies by promoting interoperability and improving data quality and accuracy of children and youth, according to guidelines of the World Health Organisation. Thus, ensure comprehensive health assessments and screenings for children, including timely follow-up and communication of results. And implement effective vaccination schedules and strategies, ensuring timely administration of vaccines and prompt response to any concerns or adverse events. Developmental milestones can be continuously monitored. This can improve care coordination, enhance decision-making, and optimise health outcomes for children. In conclusion, using interoperable electronic child health data holds great promise in advancing international child healthcare systems and enhancing the child's care and well-being. By promoting standardised data exchange, interoperability enables timely health assessments, accurate vaccination schedules, continuous monitoring of developmental milestones, coordination of care, and collaboration among child healthcare professionals and the individual or their caregiver. Embracing interoperability is essential for creating a person-centric and data-driven healthcare ecosystem where the potential of digitalisation and innovation can be fully realized.

Platelet-Derived Biomarkers: Potential Role in Early Pediatric Serious Bacterial Infection and Sepsis Diagnostics.

Fever is the most common complaint of children who are attending a pediatric emergency department (PED). Most of the fever cases are of viral origin; however, the most common markers, such as leucocyte, neutrophil count, or C-reactive protein, are not sensitive or specific enough to distinguish the etiology of fever, especially if children present at the early phase of infection. Currently, platelets have been attributed a role as important sentinels in viral and bacterial infection pathogenesis. Thus, our aim was to analyze different platelet indices, such as PNLR (platelet-to-neutrophil/lymphocyte ratio), PNR (platelet-to-neutrophil ratio) as well as specific secreted proteins, such as sP-selectin, CXCL4, CXCL7, and serotonin. We included 68 children who were referred to PED with the early onset of fever (<12 h). All children with comorbidities, older than five years, and psychiatric diseases, who refused to participate were excluded. All the participants were divided into viral, bacterial, or serious bacterial infection (SBI) groups. All the children underwent blood sampling, and an additional sample was collected for protein analysis. Our analysis revealed statistically significant differences between leucocyte, neutrophil, and CRP levels between SBI and other groups. However, leucocyte and neutrophil counts were within the age norms. A higher PNLR value was observed in a bacterial group, PNR-in viral. As we tested CXCL7 and sP-selectin, alone and together those markers were statistically significant to discriminate SBI and sepsis from other causes of infection. Together with tachypnoe and SpO2 < 94%, it improved the prediction value of sepsis as well as SBI. CXCL4 and serotonin did not differ between the groups. Concluding, CXCL7 and sP-selectin showed promising results in early SBI and sepsis diagnosis.

Effect of stimulated platelets in COVID-19 thrombosis: Role of alpha7 nicotinic acetylcholine receptor.

Since early 2020, SARS-CoV-2-induced infection resulted in global pandemics with high morbidity, especially in the adult population. COVID-19 is a highly prothrombotic condition associated with subsequent multiorgan failure and lethal outcomes. The exact mechanism of the prothrombotic state is not well understood and might be multifactorial. Nevertheless, platelets are attributed to play a crucial role in COVID-19-associated thrombosis. To date, platelets' role was defined primarily in thrombosis and homeostasis. Currently, more focus has been set on their part in inflammation and immunity. Moreover, their ability to release various soluble factors under activation as well as internalize and degrade specific pathogens has been highly addressed in viral research. This review article will discuss platelet role in COVID-19-associated thrombosis and their role in the cholinergic anti-inflammatory pathway. Multiple studies confirmed that platelets display a hyperactivated phenotype in COVID-19 patients. Critically ill patients demonstrate increased platelet activation markers such as P-selectin, PF4, or serotonin. In addition, platelets contain acetylcholine and express α7 nicotinic acetylcholine receptors (α7nAchR). Thus, acetylcholine can be released under activation, and α7nAchR can be stimulated in an autocrine manner and support platelet function. α7 receptor is one of the most important mediators of the anti-inflammatory properties as it is associated with humoral and intrinsic immunity and was demonstrated to contribute to better outcomes in COVID-19 patients when under stimulation. Hematopoietic α7nAchR deficiency increases platelet activation and, in experimental studies, α7nAchR stimulation can diminish the pro-inflammatory state and modulate platelet reactiveness via increased levels of NO. NO has been described to inhibit platelet adhesion, activation, and aggregation. In addition, acetylcholine has been demonstrated to decrease platelet aggregation possibly by blocking the e p-38 pathway. SARS-CoV-2 proteins have been found to be similar to neurotoxins which can bind to nAChR and prevent the action of acetylcholine. Concluding, the platelet role in COVID-19 thrombotic events could be explained by their active function in the cholinergic anti-inflammatory pathway.

Cartilage regeneration using improved surface electrospun bilayer polycaprolactone scaffolds loaded with transforming growth factor-beta 3 and rabbit muscle-derived stem cells.

Polycaprolactone (PCL) has recently received significant attention due to its mechanical strength, low immunogenicity, elasticity, and biodegradability. Therefore, it is perfectly suitable for cartilage tissue engineering. PCL is relatively hydrophobic in nature, so its hydrophilicity needs to be enhanced before its use in scaffolding. In our study, first, we aimed to improve the hydrophilicity properties after the network of the bilayer scaffold was formed by electrospinning. Electrospun bilayer PCL scaffolds were treated with ozone and further loaded with transforming growth factor-beta 3 (TGFß3). In vitro studies were performed to determine the rabbit muscle-derived stem cells' (rMDSCs) potential to differentiate into chondrocytes after the cells were seeded onto the scaffolds. Statistically significant results indicated that ozonated (O) scaffolds create a better environment for rMDSCs because collagen-II (Coll2) concentrations at day 21 were higher than non-ozonated (NO) scaffolds. In in vivo studies, we aimed to determine the cartilage regeneration outcomes by macroscopical and microscopical/histological evaluations at 3- and 6-month time-points. The Oswestry Arthroscopy Score (OAS) was the highest at both mentioned time-points using the scaffold loaded with TGFß3 and rMDSCs. Evaluation of cartilage electromechanical quantitative parameters (QPs) showed significantly better results in cell-treated scaffolds at both 3 and 6 months. Safranin O staining indicated similar results as in macroscopical evaluations-cell-treated scaffolds revealed greater staining with safranin, although an empty defect also showed better results than non-cell-treated scaffolds. The scaffold with chondrocytes represented the best score when the scaffolds were evaluated with the Mankin histological grading scale. However, as in previous in vivo evaluations, cell-treated scaffolds showed better results than non-cell-treated scaffolds. In conclusion, we have investigated that an ozone-treated scaffold containing TGFß3 with rMDSC is a proper combination and could be a promising scaffold for cartilage regeneration.

Overuse of medical care in paediatrics: A survey from five countries in the European Academy of Pediatrics.

Studies and initiatives such as the "Choosing wisely" (CW) campaign emphasise evidence-based investigations and treatment to avoid overdiagnosis and overtreatment. The perception of the extent of medical overactivity among professionals and drivers behind are not well studied in the paediatric field. Aim: We aimed to investigate the physicians' opinion and clarify the main drivers regarding medical overactivity in member countries of the European Academy of Paediatrics (EAP). Methods: In this study, paediatricians, paediatric residents, primary care paediatricians, and family doctors treating children were surveyed in Norway, Lithuania, Ukraine, Italy, and Switzerland. Over-investigation was defined as "diagnostic work-up or referral that is unlikely to provide information which is relevant for a patient" and overtreatment was defined as "treatment that does not benefit or can harm more than benefit the patient." The original questionnaire was developed in 2018 by a working group from the Norwegian Paediatric Association. Results: Overall, 1,416 medical doctors participated in the survey, ranging from 144 in Lithuania to 337 in Switzerland. 83% stated that they experienced over-investigation/overtreatment, and 81% perceived this as a problem. The majority (83%) perceived expectations from family and patients as the most important driver for overtreatment in their country. Other drivers for overuse were use of national guidelines/recommendations, worry for reactions, and reduction of uncertainty. Conclusion: This is the first study investigating knowledge and attitude toward medical overactivity in European countries. Despite different cultural and economic environments, the patterns and drivers of increased investigations and medicalisation are similar.

Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study.

BACKGROUND: During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. METHODS AND FINDINGS: Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. CONCLUSIONS: Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell. TRIAL REGISTRATION: ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258.

Functionalized Electrospun Scaffold-Human-Muscle-Derived Stem Cell Construct Promotes In Vivo Neocartilage Formation.

Polycaprolactone (PCL) is a non-cytotoxic, completely biodegradable biomaterial, ideal for cartilage tissue engineering. Despite drawbacks such as low hydrophilicity and lack of functional groups necessary for incorporating growth factors, it provides a proper environment for different cells, including stem cells. In our study, we aimed to improve properties of scaffolds for better cell adherence and cartilage regeneration. Thus, electrospun PCL-scaffolds were functionalized with ozone and loaded with TGF-ß3. Together, human-muscle-derived stem cells (hMDSCs) were isolated and assessed for their phenotype and potential to differentiate into specific lineages. Then, hMDSCs were seeded on ozonated (O) and non-ozonated ("naïve" (NO)) scaffolds with or without protein and submitted for in vitro and in vivo experiments. In vitro studies showed that hMDSC and control cells (human chondrocyte) could be tracked for at least 14 days. We observed better proliferation of hMDSCs in O scaffolds compared to NO scaffolds from day 7 to day 28. Protein analysis revealed slightly higher expression of type II collagen (Coll2) on O scaffolds compared to NO on days 21 and 28. We detected more pronounced formation of glycosaminoglycans in the O scaffolds containing TGF-ß3 and hMDSC compared to NO and scaffolds without TGF-ß3 in in vivo animal experiments. Coll2-positive extracellular matrix was observed within O and NO scaffolds containing TGF-ß3 and hMDSC for up to 8 weeks after implantation. These findings suggest that ozone-treated, TGF-ß3-loaded scaffold with hMDSC is a promising tool in neocartilage formation.

HMGB1: A Potential Target of Nervus Vagus Stimulation in Pediatric SARS-CoV-2-Induced ALI/ARDS.

From the start of pandemics, children were described as the ones who were less affected by SARS-Cov-2 or COVID-19, which was mild in most of the cases. However, with the growing vaccination rate of the adult population, children became more exposed to the virus and more cases of severe SARS-CoV-2-induced ARDS are being diagnosed with the disabling consequences or lethal outcomes associated with the cytokine storm. Thus, we do hypothesize that some of the children could benefit from nervus vagus stimulation during COVID-19 ARDS through the inhibition of HMGB1 release and interaction with the receptor, resulting in decreased neutrophil accumulation, oxidative stress, and coagulopathy as well as lung vascular permeability. Moreover, stimulation through alpha-7 nicotinic acetylcholine receptors could boost macrophage phagocytosis and increase the clearance of DAMPs and PAMPs. Further rise of FGF10 could contribute to lung stem cell proliferation and potential regeneration of the injured lung. However, this stimulation should be very specific, timely, and of proper duration, as it could lead to such adverse effects as increased viral spread and systemic infection, especially in small children or infants due to specific pediatric immunity state and anatomical features of the respiratory system.

Blood biomarkers in early bacterial infection and sepsis diagnostics in feverish young children.

BACKGROUND AND OBJECTIVES: While most feverish children have self-limiting diseases, 5-10% develop a serious and potentially life-threatening bacterial infection (BI). Due to potential risk, prompt recognition of BI and sepsis in the pediatric emergency department (PED) remains a clinical priority. The aim of the study was to evaluate the role of certain cytokines and chemokines separately and in combination with routine blood tests in early BI and sepsis diagnostics at PED. MATERIALS AND METHODS: We prospectively studied children younger than 5 presenting to the PED with fever lasting for under 12 hours with high risk for serious illness. Clinical data, routine blood analysis, and inflammatory cytokine and chemokine panels were evaluated for their diagnostic abilities. Two separate analyses were carried out on the patients' data: one contrasting BI and viral infection (VI) groups, the other comparing septic and non-septic patients. RESULTS: The sample comprised 70 patients (40% with BI). IL-2 was found to be the most specific biomarker to identify BI with specificity of 100%. The best discriminative ability was demonstrated by combining IL-2, IL-6, CRP, WBC, and neutrophil count: AUC 0.942 (95% Cl 0.859-0.984). IL-10 exhibited a greater AUC (0.837. 95% CI: 0.730-0.915 p<0.05) than CRP (0.807. 95% CI: 0.695-0.895 p<0.05) when predicting sepsis and showed high specificity (98%) and moderate sensitivity (75%). CONCLUSIONS: IL-6 and IL-2 could increase the diagnostic ability of routine blood tests for predicting BI, as IL-10 raises specificity for recognizing sepsis in the early hours of disease onset.

Virus Mimetic Poly (I:C)-Primed Airway Exosome-like Particles Enter Brain and Induce Inflammatory Cytokines and Mitochondrial Reactive Oxygen Species in Microglia.

Viral infections induce extracellular vesicles (EVs) containing viral material and inflammatory factors. Exosomes can easily cross the blood-brain barrier during respiratory tract infection and transmit the inflammatory signal to the brain; however, such a hypothesis has no experimental evidence. The study investigated whether exosome-like vesicles (ELVs) from virus mimetic poly (I:C)-primed airway cells enter the brain and interact with brain immune cells microglia. Airway cells were isolated from Wistar rats and BALB/c mice; microglial cell cultures-from Wistar rats. ELVs from poly (I:C)-stimulated airway cell culture medium were isolated by precipitation, visualised by transmission electron microscopy, and evaluated by nanoparticle analyser; exosomal markers CD81 and CD9 were determined by ELISA. For in vitro and in vivo tracking, particles were loaded with Alexa Fluor 555-labelled RNA. Intracellular reactive oxygen species (ROS) were evaluated by DCFDA fluorescence and mitochondrial superoxide-by MitoSOX. ELVs from poly (I:C)-primed airway cells entered the brain within an hour after intranasal introduction, were internalised by microglia and induced intracellular and intramitochondrial ROS production. There was no ROS increase in microglial cells was after treatment with ELVs from airway cells untreated with poly (I:C). In addition, poly (I:C)-primed airway cells induced inflammatory cytokine expression in the brain. The data indicate that ELVs secreted by virus-primed airway cells might enter the brain, cause the activation of microglial cells and neuroinflammation.

Novel approach towards antimicrobial chemotherapy optimization in lower respiratory tract infections in children: An observational study.

ABSTRACT: The use of local antibiogram in guiding clinical decisions is an integral part of the antimicrobial stewardship program. Conventional antibiograms are not disease-specific, ignore the distribution of microorganisms, obscure the in-vitro efficacy interrelationships, and have limited use in polymicrobial infections.We aimed to develop an in-house empiric, disease-specific, antimicrobial prescription auxiliary for the treatment of hospitalized pediatric pneumonia patients and to present the methods which help to choose the first and the second line antimicrobial therapy, while accounting for cost and safety aspects.A retrospective single center observational study was conducted on bronchoscopy obtained sputum culture. Analysis of probabilities, variance minimization, Boolean network modeling, and dominance analysis were applied to analyze antibiogram data. The Kirby-Bauer disk diffusion method was used to test the susceptibility of all isolates. Final optimization analysis included local drug acquisition cost (standardized to price per DDD) and safety profile.Data of 145 pediatric patients hospitalized with pneumonia with 218 isolates over 5 years was collected. A combination of statistical methods such as probabilities of drug efficacy, variance minimization, Boolean network modeling, and dominance analysis can help to choose the optimal first-line and the second-line antimicrobial treatment and optimize patient care. This research reveals that ampicillin is the optimal choice as the first-line drug and piperacillin-tazobactam is the second-line antimicrobial drug if the first one is not effective, while accounting for cost and safety aspects.The paper proposes a new methodology to adapt empiric antimicrobial therapy recommendations based on real world data and accout for costs and risk of adverse events.

The Effect of Ozone Treatment on the Physicochemical Properties and Biocompatibility of Electrospun Poly(ε)caprolactone Scaffolds.

Ozonation has been proved as a viable surface modification technique providing certain properties to the scaffolds that are essential in tissue engineering. However, the ozone (O3) treatment of PCL scaffolds in aqueous environments has not yet been presented. O3 treatment performed in aqueous environments is more effective compared with traditional, executed in ambient air treatment due to more abundant production of hydroxyl radicals (•OH) within the O3 reaction with water molecules. During interaction with •OH, the scaffold acquires functional groups which improve wettability properties and encapsulate growth factors. In this study, a poly(ε)caprolactone (PCL) scaffold was fabricated using solution electrospinning and was subsequently ozonated in a water reactor. The O3 treatment resulted in the expected occurrence of oxygen-containing functional groups, which improved scaffold wettability by almost 27% and enhanced cell proliferation for up to 14 days. The PCL scaffold was able to withhold 120 min of O3 treatment, maintaining fibrous morphology and mechanical properties.