Platelet role in the prediction of MIS-C severity

IntroductionMultisystem 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 methodsWe 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.ResultsHalf 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.ConclusionsOur 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

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

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

IntroductionAvoiding 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.MethodsIn 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.ResultsOf 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.ConclusionOvertreatment 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

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

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. 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. 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. ISRCTN91495258 https://www.isrctn.com/ISRCTN91495258

Unusual case of chronic recurrent multifocal osteomyelitis

Abstract Background Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory bone disorder that primarily affects young girls, with a mean age of 10 years at onset. Generally, it is a self-limited disease. However, recent data indicate that more than 50% of patients have a chronic persistent disease and about 20% a recurring course of this condition. Also, there are more cases reported with associated auto-inflammatory and autoimmune diseases. In this case report, we present a rare case of sporadic CRMO in which the patient eventually developed C-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies)-associated renal vasculitis and hyperparathyroidism. Case presentation A 14 year old female patient was brought to the emergency department with a sudden onset of left leg pain and oedema. After physical evaluation and initial investigation, she was diagnosed with femoral and pelvic deep vein thrombosis. While searching for possible thrombosis causes, osteomyelitis of the left leg was identified. Additional CT and MRI scans hinted at the CRMO diagnosis. Due to the multifocal lesions of CRMO, endocrinological evaluation of calcium metabolism was done. The results showed signs of hyperparathyroidism with severe hypocalcaemia. Moreover, when kidney damage occurred and progressed, a kidney biopsy was performed, revealing a C-ANCA associated renal vasculitis. Treatment was started with cyclophosphamide and prednisolone according to the renal vasculitis management protocol. Severe metabolic disturbances and hyperparathyroidism were treated with alfacalcidol, calcium and magnesium supplements. Secondary glomerulonephritis (GN) associated hypertension was treated with ACE (angiotenzine converting enzyme) inhibitors. Anticoagulants were prescribed for deep vein thrombosis. After 1.5 years of treatment, the patient is free of complaints. All microelement and parathormone levels are within normal range. Kidney function is now normal. To date, there are no clinical or diagnostic signs of deep vein thrombosis. Conclusions This case report presents a complex immunodysregulatory disorder with both auto-inflammatory and autoimmune processes. We hypothesize that the long lasting active inflammation of CRMO may induce an autoimmune response and result in concomitant diseases like C-ANCA-associated vasculitis in our patient. Any potential specific pathogenic relationships between these two rare pathologies may need to be further studied. Furthermore, there is a lack of specific biomarkers for CRMO and more studies are necessary to identify CRMO’s characteristic patterns and how to best monitor disease progression

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 (&lt;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 &lt; 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

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

Functionalized Electrospun Scaffold&ndash;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&ndash;scaffolds were functionalized with ozone and loaded with TGF-&beta;3. 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 (&ldquo;na&iuml;ve&rdquo; (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-&beta;3 and hMDSC compared to NO and scaffolds without TGF-&beta;3 in in vivo animal experiments. Coll2-positive extracellular matrix was observed within O and NO scaffolds containing TGF-&beta;3 and hMDSC for up to 8 weeks after implantation. These findings suggest that ozone-treated, TGF-&beta;3-loaded scaffold with hMDSC is a promising tool in neocartilage formation

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