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.

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.

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.

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.

Early Blood Biomarkers to Improve Sepsis/Bacteremia Diagnostics in Pediatric Emergency Settings.

Background: Sepsis is the leading cause of death in children worldwide. Early recognition and treatment are essential for preventing progression to lethal outcomes. CRP and Complete Blood Count (CBC) are the initial preferred tests to distinguish between bacterial and viral infections. Specific early diagnostic markers are still missing. Aim: To investigate diagnostic value of Neutrophil-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV) and Platelet-MPV ratio (PLT/MPV) to distinguish sepsis/bacteremia and viral infection. Methods: We conducted a retrospective data analysis of case records of 115 children from 1 month to 5 years of age. All cases were divided into two groups-sepsis/bacteremia (n = 68) and viral (n = 47) patients, and further subdivided according to the time of arrival into early or late (≤12 or 12-48 h post the onset of fever, respectively). Analysis of CBC and CRP results was performed. NLR and PLT/MPV were calculated. Results: Sepsis/bacteremia group demonstrated higher absolute platelets count (370.15 ± 134.65 × 108/L versus 288.91 ± 107.14 × 108/L; p = 0.001), NLR (2.69 ± 2.03 versus 1.83 ± 1.70; p = 0.006), and PLT/MPV (41.42 ± 15.86 versus 33.45 ± 17.97; p = 0.001). PLT/MPV was increased in early arrival sepsis/bacteremia infants (42.70 ± 8.57 versus 31.01 ± 8.21; p = 0.008). NLR and MPV were significantly lower in infants (≤12 months) with viral infection on late arrival (1.16 ± 1.06 versus 1.90 ± 1.25, p = 0.025 for NLR and 8.94 ± 0.95fl versus 9.44 ± 0.85fl, p = 0.046 for MPV). Conclusion: Together with standard blood biomarkers, such as CRP, neutrophils, or platelets count, PLT/MPV is a promising biomarker for clinical practice to help discriminate between viral disease or sepsis/bacteremia in all children, especially in early onset of symptoms. NLR and MPV could support exclusion of sepsis/bacteremia in late arrival cases.

Paediatric Pain Medicine: Pain Differences, Recognition and Coping Acute Procedural Pain in Paediatric Emergency Room.

Paediatric pain and its assessment and management are challenging for medical professionals, especially in an urgent care environment. Patients in a paediatric emergency room (PER) often undergo painful procedures which are an additional source of distress, anxiety, and pain. Paediatric procedural pain is often underestimated and neglected because of various myths, beliefs, and difficulties in its evaluation and treatment. However, it is very different from other origins of pain as it can be preventable. It is known that neonates and children can feel pain and that it has long-term effects that last through childhood into adulthood. There are a variety of pain assessment tools for children and they should be chosen according to the patient's age, developmental stage, communication skills, and medical condition. Psychological factors such as PER environment, preprocedural preparation, and parental involvement should also be considered. There are proven methods to reduce a patient's pain and anxiety during different procedures in PER. Distraction techniques such as music, videogames, virtual reality, or simple talk about movies, friends, or hobbies as well as cutaneous stimulation, vibration, cooling sprays, or devices are effective to alleviate procedural pain and anxiety. A choice of distraction technique should be individualized, selecting children who could benefit from nonpharmacological pain treatment methods or tools. Nonpharmacological pain management may reduce dosage of pain medication or exclude pharmacological pain management. Most nonpharmacological treatment methods are cheap, easily accessible, and safe to use on every child, so it should always be a first choice when planning a patient's care. The aim of this review is to provide a summary of paediatric pain features, along with their physiology, assessment, management, and to highlight the importance and efficacy of nonpharmacological pain management in an urgent paediatric care setting.

Lower Airway Virology in Health and Disease-From Invaders to Symbionts.

Studies of human airway virome are relatively recent and still very limited. Culture-independent microbial techniques showed growing evidence of numerous viral communities in the respiratory microbial ecosystem. The significance of different acute respiratory viruses is already known in the pathogenesis of chronic conditions, such as asthma, cystic fibrosis (CF), or chronic obstructive lung disease (COPD), and their exacerbations. Viral pathogens, such as influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, or rhinovirus, have been associated with impaired immune response, acute exacerbations, and decrease in lung function in chronic lung diseases. However, more data have attributed a role to Herpes family viruses or the newly identified Anelloviridae family of viruses in chronic diseases, such as asthma, idiopathic pulmonary fibrosis (IPF), or CF. Impaired antiviral immunity, bacterial colonization, or used medication, such as glucocorticoids or antibiotics, contribute to the imbalance of airway microbiome and may shape the local viral ecosystem. A specific part of virome, bacteriophages, frames lung microbial communities through direct contact with its host, the specific bacteria known as Pseudomonas aeruginosa or their biofilm formation. Moreover, antibiotic resistance is induced through phages via horizontal transfer and leads to more severe exacerbations of chronic airway conditions. Morbidity and mortality of asthma, COPD, CF, and IPF remains high, despite an increased understanding and knowledge about the impact of respiratory virome in the pathogenesis of these conditions. Thus, more studies focus on new prophylactic methods or therapeutic agents directed toward viral⁻host interaction, microbial metabolic function, or lung microbial composition rearrangement.

Left atrial mechanics in patients with acute STEMI and secondary mitral regurgitation: A prospective pilot CMR feature tracking study.

BACKGROUND AND OBJECTIVE: Left atrium (LA) is an important biomarker of adverse cardiovascular outcomes and cerebrovascular events. This study aimed to evaluate LA myocardial deformation using cardiac magnetic resonance feature tracking (CMR-FT) in patients with acute ST-segment elevation myocardial infarction (STEMI) and secondary mitral regurgitation (MR). Additionally, to assess interobserver and intraobserver variability of the technique. MATERIALS AND METHODS: Twenty patients with STEMI underwent CMR with a 1.5Tesla MRI scanner. According to the presence of MR patients were divided into two groups: MR(+) and MR(-). Total LA strain (ɛs), passive LA strain (ɛe), and active LA strain (ɛa) were obtained. Additionally, total, passive and active strain rates (SRs, SRe, and SRa) were calculated. To assess interobserver agreement data analysis was performed by second independent observer. RESULTS: LA volumetric and functional parameters were similar in both groups. All LA strain values were significantly higher in patients with MR: ɛs (27.67±10.25 for MR(-) vs. 32.80±6.95 for MR(+); P=0.01), ɛe (15.29±7.30 for MR(-) vs. 19.22±6.04 for MR(+); P=0.01) and ɛa (12.38±4.23 for MR(-) vs. 14.44±5.19 for MR(+); P=0.03). Only SRe significantly increased in patients with MR (-0.57±0.24 for MR(-) vs. -0.70±0.20 for MR(+); P=0.01). All LA deformation parameters demonstrated high interobserver and intraobserver agreement. CONCLUSIONS: Conventional volumetric and functional LA parameters do not detect early changes in LA performance in patients with STEMI and secondary MR. In contrast, LA reservoir, passive and active strain are significantly higher in patients with MR. Only peak early negative strain rate substantially increases during secondary MR. LA deformation parameters derived from conventional cine images using CMR-FT technique are highly reproducible.

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.

Younger Children with Respiratory Tract Infections Are More Exposed to Off-Label Treatments: An Exploratory Retrospective Study in a Pediatric Emergency Setting.

Off-label drug use is prevalent in the pediatric population and represents a patient safety concern. We aimed to identify factors for off-label drug use in our pediatric emergency department (PED). METHODS: We performed a retrospective data analysis. All patients aged 0-18 referred to PED from 1 September to 1 October 2022, were included. Further analysis was performed when respiratory tract infections were diagnosed. DATA COLLECTED: gender, age, triage group, chronic diseases, vital signs, and PED-prescribed treatment (medications, dosages, methods of administration). Statistical analysis used SPSS 28.0, with significance at p < 0.05. RESULTS: Data from 473 patients were analyzed, median age 3.5 years. Chronic diseases were present in 17.1% of children. 387 medications were prescribed, 47.5% being off-label. Off-label treatment was common for external otitis, acute laryngitis, and acute bronchitis (p < 0.001). There was incorrect administration of tobramycin with dexamethasone for otitis (n = 16, 100%) and inappropriate use of salbutamol inhalations by age (34.8%, n = 16). Some medications were given orally instead of injections (ondansetron n = 5, 62.5%; dexamethasone n = 82, 98.7%) or intranasally instead of intravenously (IV) (midazolam n = 7, 87.5%). IV adrenalin was prescribed for inhalations (n = 46). Younger children were more likely to receive off-label treatment (p < 0.001). CONCLUSION: Our study highlights the widespread issue of off-label and unlicensed drug prescribing in pediatric emergency care. Further research is necessary, because this reliance on off-label prescribing raises concerns about patient safety and compliance, especially given the limited clinical trials and therapeutic options available.

The importance of ultrasound examination in care of juvenile idiopathic arthritis patients: 9 months follow-up study.

Introduction: Juvenile idiopathic arthritis (JIA) is a group of rare musculoskeletal disorders with chronic inflammation of joints, typically manifesting before the age of 16 years. The assessment of disease activity remains pivotal in JIA treatment decisions, particularly during clinical remission. While musculoskeletal ultrasound (MSUS) has shown promise in detecting subclinical synovitis, longitudinal data on MSUS features in JIA remains limited. The aim of this study was to evaluate the prevalence of subclinical synovitis observed in MSUS over a follow-up period in JIA patients. Additionally, it sought to assess the consistency and correlation between clinical findings, standardized composite clinical score (JADAS10), and MSUS-detected synovitis during 9 months follow-up. Patients and methods: a prospective single-center study was conducted, enrolling all consecutive JIA patients (excluding systemic JIA) seen at the study center in one year period. At three-months intervals over a 9 months period (M0, M3, M6 and M9), patients underwent clinical examination, laboratory tests, and MSUS assessment. Data on demographic characteristics, disease profile, and treatment were collected. Patients were categorized into active disease (ACT) or remission (REM) groups based on Wallace criteria and JADAS10 scores using previously validated thresholds. The ultrasound assessments adhered to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) pediatric group, covering 40 joints, were performed by two ultrasonographers at every visit. Subclinical synovitis was defined as synovitis detected exclusively by MSUS. Spearman's correlation coefficients (rs) were used to evaluate the association between MSUS, clinical data, and outcome measures, such as active joint count (ACJ), patient's/parent's global assessment of disease activity (PaGA), physician's global assessment of disease activity (PhGA) and JADAS10. Results: subclinical synovitis was evident in 5.2% of all joints and in 80.6% of the patients at baseline. During the follow-up period, signs of subclinical synovitis decreased to 3.8% of joints, however, the proportion of affected patients remained high (67.7%), with the majority in REM group. Despite the consistent strong correlation between PaGA and PhGA throughout the study (rs > 0.895; p < 0.001), both measures displayed moderate (rs = 0.647; p < 0.001) to weak (rs = 0.377; p = 0.04) correlations with MSUS findings. Notably, PaGA remained significantly correlated with MSUS at the M9 visit (rs = 0.377, p = 0.04), while PhGA showed no correlation (p = 0.094). Conclusions: The study results indicate the persistence of subclinical inflammation detected by MSUS in a significant proportion of JIA patients, even during clinical remission. Moreover, the findings suggest that conventional measurements of JIA activity may be insufficient for assessing patients in clinical remission.

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.

A mediastinal mass mimicking asthma symptoms.

Extramedullary myeloid sarcoma is a rare form of myelogenous leukemia. It can involve any anatomical body part. Mediastinal involvement is reported in only few cases. We report on a case of extramedullary myeloid sarcoma presenting as a mediastinal mass in a previously healthy nonleukemic male teenager with primary asthmatic complaints and the signs of superior vena cava syndrome.

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.

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.

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.

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.

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.

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.