Dilemmas on emicizumab in children with haemophilia A: A survey of strategies from PedNet centres.

INTRODUCTION: Haemophilia A care has changed with the introduction of emicizumab. Experience on the youngest children is still scarce and clinical practice varies between haemophilia treatment centres. AIM: We aimed to assess the current clinical practice on emicizumab prophylaxis within PedNet, a collaborative research platform for paediatricians treating children with haemophilia. METHODS: An electronic survey was sent to all PedNet members (n = 32) between October 2022 and February 2023. The survey included questions on the availability of emicizumab, on the practice of initiating prophylaxis in previously untreated or minimally treated patients (PUPs or MTPs) and emicizumab use in patients with or without inhibitors. RESULTS: All but four centres (28/32; 88%) responded. Emicizumab was available in clinical practice in 25/28 centres (89%), and in 3/28 for selected patients only (e.g. with inhibitors). Emicizumab was the preferred choice for prophylaxis in PUPs or MTPs in 20/25 centres; most (85%) started emicizumab prophylaxis before 1 year of age (30% before 6 months of age) and without concomitant FVIII (16/20; 80%). After the loading dose, 13/28 centres administered the recommended dosing, while the others adjusted the interval of injections to give whole vials. In inhibitor patients, the use of emicizumab during ITI was common, with low-dose ITI being the preferred protocol. CONCLUSION: Most centres choose to initiate prophylaxis with emicizumab before 12 months of age and without concomitant FVIII. In inhibitor patients, ITI is mostly given in addition to emicizumab, but there was no common practice on how to proceed after successful ITI.

First detected geographical cluster of BoDV-1 encephalitis from same small village in two children: therapeutic considerations and epidemiological implications.

BACKGROUND: The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. METHODS AND RESULTS: A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. CONCLUSION: Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation.

Teamwork and mental workload in postsurgical pediatric patient handovers: Prospective effect evaluation of an improvement intervention for OR-PICU patient transitions.

Postsurgical handover of pediatric patients from operating rooms (OR) to pediatric intensive care units (PICU) is a critical step. This transition is susceptible to errors and inefficiencies particularly if poor multidisciplinary teamwork occurs. Despite wide adoption of standardized handover interventions, comprehensive investigations into joint effects for patient care and provider outcomes are scarce. We aimed to improve OR-PICU handovers quality and sought to evaluate the intervention with particular attention to patient care effects and provider outcomes. A prospective, before-after-study design with an interrupted-series and a multi-source, mixed-methods evaluation approach was established. Drawing upon a participative plan-do-study-act approach, a standardized, checklist-based handover process was designed and implemented. For effect assessments, we observed OR-PICU handovers on site (pre implementation: n = 31, post: n = 30), respectively, with standardized expert observation and provider self-report tools (n = 111, n = 110). Setting was a tertiary Pediatric University Hospital. Supplementary qualitative, semi-structured interviews were conducted, and a general inductive content analysis approach was used to identify key facilitators and barriers on implementation. Improvement efforts focused on stepwise implementation of (1) standardized handover process and (2) a checklist for multi-professional OR-PICU handover communication. We observed significant increases in team and patient setup (pre: 79.3%, post: 98.6%, p < .01), enhanced team engagement (pre: 50%, post: 81.7%, p < .01), and comprehensive information transfer by the anesthesia sub-team (pre: 78.6%, post: 87.3%, p < .01). Expert-rated teamwork outcomes were consistently higher, yet self-reported teamwork did not change over time. Provider perceived stress and disruptions did not change, mental workload tended to decrease over time (pre: M = 3.2, post: 2.9, p = .08). Comprehensiveness of post-operative patient information reported by PICU physician increased significantly: pre: 65.9%, post: 76.2%, p < .05. After implementation, providers acknowledged the importance of standardized handover practices and associated benefits for facilitation of information transfer and comprehensiveness. Among reported barriers were obstacles during implementation as well as insufficient consideration of professionals' individual workflow after surgery. CONCLUSION:  A multidisciplinary intervention for postsurgical pediatric patient handovers was associated with improved expert-rated teamwork and fewer omissions of key patient information over time. Inconsistent results were obtained for provider-rated mental workload and teamwork outcomes. The findings contribute to a better understanding concerning the interplay of teamwork and provider cognitions in the course of establishing safe patient transitions in pediatric care. WHAT IS KNOWN: • Transfer of critically ill children conveys significant challenges for interprofessional communication and teamwork. Prospective research into interventions for safe and efficient handover practices of OR PICU patient transitions is necessary. • Checklists are assumed to facilitate cognitive load among providers in acute clinical environments. WHAT IS NEW: • A standardized, checklist-based handover intervention was associated with improvements in team set-up and information transfer. Provider outcomes such as mental workload and stress did not change over time. • The combination of teamwork and provider assessments allows a more nuanced understanding of implementation barriers and sustainable effects in course of OR-PICU handover interventions.

Electronic diaries in the management of haemophilia gene therapy: Perspective of an expert group from the German, Austrian and Swiss Society on Thrombosis and Haemostasis (GTH).

INTRODUCTION: Gene therapy (GT) is becoming a realistic treatment option for patients with haemophilia. Outside clinical trials, the complexity and potential complications of GT will pose unprecedented challenges to haemophilia care centres. AIM: To explore the potential use of electronic tools to improve the delivery of GT under real-world conditions. METHODS: Considering the hub-and-spoke model, the GTH working group on GT considered the entire patient pathway and reached consensus on requirements for an integrative software tool to secure documenting and sharing information between treaters, pharmacies and patients. RESULTS: Six steps of the gene therapy process were identified, each requiring completion of the previous step as a prerequisite for entry. The responsibilities of GT dosing and follow-up treatment centres, read/write access rules, and the minimum data set were outlined. Data contributed by patients through mobile devices was also considered. CONCLUSION: Important information needs to be shared between patients and treatment centres in a real-world GT hub-and-spoke model. Collecting and sharing this information in well-organised electronic applications will not only improve patient care but also enable national and international data collection in clinical registries.

The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.

[Arterial ischemic stroke in childhood and adolescence : Time-critical emergency in pediatrics]. / Arteriell ischämischer Schlaganfall im Kindes- und Jugendalter : Zeitkritischer Notfall in der Pädiatrie.

Childhood arterial ischemic stroke is one of the most time-critical pediatric emergencies but is often diagnosed with a prognostically relevant time delay. The reasons are low awareness, sometimes unspecific clinical presentation with a wide variety of critical differential diagnoses and less coordinated acute care structures. The revascularization strategies established for adults also show sometimes spectacular success in children. These should therefore also be made available for affected children if possible, although the evidence is nowhere near comparable. In the postacute phase the etiological work-up is complex due to the risk factors which need to be considered, but identification of the individual risk profile is essential as it defines secondary prevention, risk of recurrence and outcome. The long-term care in a multiprofessional, interdisciplinary team must take into account all bio-psycho-social aspects of the child in the current developmental phase.

[Impact of COVID-19 Pandemic on Medical Care of Patients with Inherited Bleeding Disorders]. / Auswirkungen der COVID-19 Pandemie auf die medizinische Versorgung von Patienten mit angeborenen Blutungsneigungen.

BACKGROUND AND OBJECTIVES: Chronic diseases, such as inherited bleeding disorders (IBD) are often associated with high costs of medical care. COVID-19 containment measures, including isolation and triage, led to restrictions in the health care of chronically ill patients. The aim of the present study was to investigate the effects of the COVID-19 pandemic on the health care of IBD patients. METHODS: In this multicentre cross-sectional study to evaluate the effects of COVID-19 on the mental health and quality of care of patients with inherited bleeding disorder, an ad hoc questionnaire was sent to 586 patients/parents of children with haemophilia A, B or von Willebrand syndrome type 3. In addition to demographic and clinical data, patients/parents of patients with inherited bleeding disorders were asked about their thoughts, concerns and experiences regarding their medical care during the COVID-19 pandemic. Differences between clinical subgroups were calculated. RESULTS: Significant differences were found between subgroups (severity, type of therapy, product class, comorbidities) with regard to the transmission of COVID-19 through plasma products, the effects of COVID-19 positive test results, fear of getting COVID-19, delayed drug supply and physiotherapy treatment. DISCUSSION: The medical care of patients with inherited bleeding disorders, who need a continuous supply of essential drugs, is a particular challenge in times of pandemics. Therefore, worries and fears of IBD patients should be taken seriously and innovative communication channels established to maintain therapy standards and quality of care.

Impact of COVID-19 pandemic on mental health of patients with inherited bleeding disorders in Germany.

BACKGROUND: The worldwide pandemic spread of SARS-CoV-2 can lead to either respiratory infection or containment-associated isolation with possible higher impact on chronic diseases such as inherited bleeding disorders (IBD). The aim of the study was to evaluate the impact of COVID-19 on patients and caregivers of IBD patients regarding their concerns and worries related to own health, access to treatment and availability of factor concentrates and their experiences related to medical care. METHODS: Multicentre, cross-sectional study evaluating the impact of COVID-19 on mental health of IBD patients. An ad hoc questionnaire was developed and sent to 586 patients/caregivers with haemophilia A, haemophilia B and VWD type III. The survey included information on demographic and clinical data, needs, concerns and experiences regarding medical care during COVID-19 pandemic. RESULTS: In total, 355 of the IBD-Group (200 patients, 155 caregivers) completed the survey (61.7% response rate). Most patients suffered from haemophilia A (73.8%) and were severely affected (64.7%). Eleven patients were in quarantine due to suspected COVID-19; none had symptoms. One quarter worried (very) strongly about getting the coronavirus, 71.3% asked themselves what will happen to them when they will get COVID-19, 40.1% felt unchanged, and 18.9% worried about delivery difficulties of their IBD treatment product. In 52.8%, medical appointments were postponed. Significant differences between caregivers and patients were found in most aspects. DISCUSSION: The IBD patients affected by a chronic disorder have particular thoughts and worries regarding COVID-19. Haemophilia specialists should be committed to address these concerns and guarantee treatment despite containment strategies.

Assessing prophylactic use and clinical outcomes in hemophilia A patients treated with rVIII-SingleChain and other common rFVIII products in Germany.

OBJECTIVE: To evaluate real-world outcomes with rVIII-SingleChain and other commonly used recombinant FVIII (rFVIII) products. METHODS: Hemophilia treatment centers in Germany (n = 21) contributed patient chart data. Inclusion criteria were prophylactic treatment with one of five rFVIII products for ≥8 weeks. RESULTS: Male patients (n = 225) were included: rVIII-SingleChain (n = 40), rFVIIIFc (n = 47), octocog alfa (rFVIII; n = 58), octocog alfa (BAY 81-8973; n = 40), or moroctocog alfa (n = 40). In patients with severe disease (n = 76), 66.6%, 70.0%, 20.0%, 7.7%, and 27.3% were dosed ≤2×/week, respectively. Irrespective of dosing frequency, mean annualized bleed rates (ABRs)/annualized spontaneous bleed rates (AsBRs) were 0.3/0.1, 0.8/0.4, 1.1/0.5, 1.5/0.8, and 1.4/0.6, and mean FVIII consumption (IU/kg/week) was 83.2, 97.2, 92.5, 104.0, and 102.1, respectively. Results for all patients were similar. Of the patients on prophylaxis with prior therapy and after switching to rVIII-SingleChain (n = 21), mean ABR/AsBRs were 0.7/0.3 and 0.2/0.0, respectively. After switching to rVIII-SingleChain, mean FVIII consumption reduced (109.4 vs 74.5 IU/kg/week), and percentage of patients dosed ≤2×/week increased (0% to 71.4%). CONCLUSIONS: rVIII-SingleChain prophylaxis provides excellent bleeding protection, with potentially lowest factor consumption among the products assessed. Patients who switched to rVIII-SingleChain prophylaxis reduced dosing frequency and consumption compared with prior treatment, with similar or potentially lower bleeding rates.

Symptom patterns in childhood arterial ischemic stroke: Analysis of a population-based study in Germany.

HINTERGRUND: Die zeitliche Verzögerung zwischen Symptombeginn und Diagnose ist eine Herausforderung in der Behandlung von Kindern mit arteriell ischämischem Schlaganfall. Frühere Studien zur klinischen Präsentation beschäftigten sich v. a. mit kumulativen Symptomen. ZIELSETZUNG: Ziel dieser Studie ist es, mögliche Symptommuster aufzuzeigen. METHODEN: In einer aktiven Beobachtungsstudie zwischen 01/2015 und 12/2016 (ESPED-Studie) wurden Kinder mit Erstdiagnose eines arteriell ischämischen Schlaganfalls eingeschlossen. Isoliert auftretende Erstsymptome wurden verschiedenen Symptomkombinationen gegenübergestellt. Zudem wurde untersucht, inwieweit ein als "akut" oder "progredient" klassifiziertes Auftreten der Symptome Rückschlüsse auf die zugrundeliegende Ätiologie erlaubt. ERGEBNISSE: Es wurden 99 Kinder in die Studie eingeschlossen. Unabhängig vom Alter traten überwiegend fokale Symptome auf (86%). Krampfanfälle als Initialsymptom wurden insbesondere bei Säuglingen beschrieben (67%), wohin-gegen diffuse, unspezifische Symptome vor allem bei Vorschulkindern (38%) und älteren Kindern (59%) auftraten. Isoliert traten fokale Symptome bei 37 Kindern auf, 48 Kinder zeigten zusätzlich unspezifische Symptome, darunter auch 9 Kinder mit Krampfanfällen. Isolierte unspezifische Symptome zeigten sich lediglich bei 7 Kindern, 2 Kinder wurden nur mit Krampfanfällen symptomatisch. Die Akuität des Symptombeginns wurde bei 53/78 als "akut" und bei "25/78 Fällen als "progredient" klassifiziert, lieferte jedoch keinen Hinweis auf die zugrundeliegende Ätiologie. SCHLUSSFOLGERUNG: Jedes neue fokal neurologische Defizit sollte unabhängig vom Auftreten (isoliert oder kombiniert, akut oder progredient) an einen kindlichen Schlaganfall denken lassen. BACKGROUND: Time delay between onset of clinical symptoms and diagnosis is a challenge in childhood arterial ischemic stroke. Most previous studies reported cumulative symptoms. OBJECTIVE: We attempted to identify typical symptom patterns and assessed their emergence in childhood stroke. METHODS: Prospective active surveillance in ESPED, a hospital based Pediatric Surveillance Unit for rare diseases in Germany, between January 2015 and December 2016. Case definition: first diagnosis of a radiologically confirmed arterial ischemic stroke. Symptom patterns were identified as occurring in isolation or in combination. We distinguished acute vs. progressive onset. We ascertained risk factors to identify the possible etiology. RESULTS: 99 children with childhood arterial ischemic stroke were reported. Focal symptoms were the predominant presenting feature (86%), independent of age. Seizures were more often seen in infants < 1 year (67%), whereas diffuse symptoms were more present in pre-school children (38%) and older children (59%). 37 children had focal features alone and 48 additional non-specific features, including 9 with seizures. Isolated non-specific features accounted for 7 cases, and 2 children had (focal) seizures as the only symptom. In 77% of all cases at least one risk factor was identified. The emergence of symptoms was acute in 53/78 cases and progressive in 25/78 cases. The pattern of emergence was unrelated to the underlying etiology. CONCLUSIONS: Any new focal neurological deficit in isolation, or associated with seizures or further non-specific symptoms should alert to childhood stroke.

Perioperative management of hemostasis in children and adolescents.

Invasive procedures in children are in most cases elective and are carried out in otherwise healthy children. While many surgeries are still performed in a hospital, more and more procedures are defined as "outpatient procedures," leading to increased discussion about safety and risks. This review will examine common practices, review the sparse literature and provide recommendations regarding the identification of children with increased bleeding risk, planning for children with known bleeding disorders and strategies for perioperative management. In conclusion, after careful planning, surgeries can be performed safely even in children with known bleeding disorders.

Neonatal Arterial Ischemic Stroke - A Hospital Based Active Surveillance Study in Germany.

Background Neonatal arterial ischemic stroke (NAIS) accounts for substantial long term sequelae in children. The potential effectiveness of neuroprotective therapies needs to be evaluated in appropriate studies with sufficient power. Objective To identify annual number of NAIS cases in Germany potentially eligible for randomized interventional trials. Methods Active surveillance for NAIS in 345 pediatric hospitals with questionnaire based validation of reported cases. Results Incidence of NAIS (7.1/100000 births) was in the range of other population-based studies. To design future clinical trials with anticoagulative or regenerative therapies, it is of major importance to distinguish between cases with or without relevant perinatal pathology. Children without underlying disease or premature birth accounted for 56% of all reported NAIS cases (primary NAIS). In 69% of the primary cases clinical seizures were observed. Although 31% showed other, less pathognomonic symptoms, NAIS was diagnosed. Mean time span between onset of symptoms and diagnosis was 2.9 days. The sensitivity of the initial ultrasound performed in all cases was 69%. Conclusions NAIS is a rare but not negligible morbidity in newborns. Asymptomatic children account for 56% of NAIS in all neonates. In these, not only seizures but also other unexplained symptoms should trigger diagnostic work-up with cUS and cMRI. Negative initial ultrasound results do not exclude NAIS.

Subcutaneous protein C concentrate in the management of severe protein C deficiency--experience from 12 centres.

Since the first description of subcutaneous protein C concentrate as treatment for severe protein C deficiency in 1996, further cases have been reported but there is no uniform approach to this form of treatment. In order to assess the safety and effectiveness of subcutaneous protein C concentrate and suggest recommendations for future use, patients who had received subcutaneous protein C concentrate were identified from the literature, by contacting the manufacturers and by personal communication. Treatment details were available from 14 cases. Apart from one case where the infusion interval was inadvertently increased, no thrombotic events occurred even when doses were subsequently reduced. Initially, a trough protein C level of >0·25 iu/ml should be aimed for. Subsequently, a smaller dose of subcutaneous protein C concentrate, especially if taken with an oral anticoagulant, may be protective maintenance treatment. The treatment was well tolerated with few side effects. Subcutaneous protein C concentrate on its own or combined with an oral anticoagulant appears to be safe and effective as maintenance treatment of severe protein C deficiency. A major advantage is the avoidance of central venous access devices. The incidence of neurodevelopmental handicap was high with blindness affecting the majority of patients.

Patient perspective on living with mild hemophilia in Germany: results from a nationwide survey.

Introduction: The disease burden and bleeding risk of patients with mild hemophilia may be underestimated. Their health-related quality of life (QoL) may be negatively impacted by insufficient treatment and bleed-related joint damage connected to a potentially delayed diagnosis. Aim: This study aims to gain information on the care reality and QoL of patients aged ≥12 years with mild hemophilia in Germany. Methods: An anonymous cross-sectional patient survey using standardized questionnaires was conducted in a validated electronic patient-reported outcome system. Medical specialists, hemophilia centers, patient organizations, and support groups across Germany invited the patients. Results: A total of 43 patients (35 patients with hemophilia A, 5 patients with hemophilia B, and 3 patients for whom the information was missing) with a median age of 33 years were analyzed. The median age at diagnosis was 6.0 years (interquartile range [IQR] 2.0-15.0), and the median factor activity was 14.0% (IQR 12.0-25.0). Nearly 85% of the patients received factor concentrates in the past, and the most common reasons for the treatment were surgery or joint bleeding (each 65.6%). Half of the patients who provided feedback experienced complications during bleeding episodes. Prophylactic treatment with factor concentrates was rare (10.3%). The patients had minor problems regarding their health status. Conclusion: Bleeding complications and joint bleeding, in particular, may be highly underestimated in patients with mild hemophilia, highlighting a medical need in this population. Patients with a potential benefit from prophylaxis need to be identified. Mild hemophilia has a negative impact on patients' QoL. Hemophilia centers satisfied the patients' needs. Further research is needed to address the current lack of awareness and improve adequate treatment in the future.

Unravelling the spectrum of von Willebrand factor variants in quantitative von Willebrand disease: results from a German cohort study.

BACKGROUND: Von Willebrand disease (VWD), the most prevalent hereditary bleeding disorder, results from deficiency of von Willebrand factor (VWF). OBJECTIVES: This large cohort study aims to offer a comprehensive exploration of mutation spectra and laboratory features in quantitative VWF deficiencies, shedding light on genetic underpinnings and genotype-phenotype associations. METHODS: Our cohort consisted of 221 Caucasian index patients with quantitative VWD, along with 47 individuals whose plasma VWF levels fell within the lower normal boundaries (50-70 IU/dL). We conducted comprehensive VWF assays and genetic analyses, encompassing VWF gene sequencing, copy number variation investigations, and bioinformatic assessments. RESULTS: Following International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee VWF guidelines, 77 index patients were characterized as having type 1 VWD (VWF antigen [VWF:Ag] < 30 IU/dL), 111 as having type 1 VWD (VWF:Ag, 30-50 IU/dL), and 33 as having type 3 VWD. Mutation detection rates were 88%, 65%, and 92%, respectively. Notably, blood group O overrepresentation was evident in type 1 with VWF:Ag of 30 to 50 IU/dL, particularly among mutation-negative patients, suggesting a potential causal role of blood group O. A total of 223 VWF variants, comprising 147 distinct variations, were identified in quantitative VWD patients, of which 57 were novel variants (39%). Additionally, approximately 70% of individuals with VWF levels within the lower normal boundaries (50-70 IU/dL) displayed VWF variants. CONCLUSION: Our data advance our understanding of the molecular mechanisms underlying quantitative VWD, offering valuable insights for future research and clinical management. Distinct mutation patterns were observed among subgroups, particularly the contrast between type 1 VWD (VWF:Ag < 30 IU/dL) and type 1 VWD (VWF:Ag, 30-50 IU/dL), an area with limited prior investigation.

Endovascular thrombectomy for childhood stroke (Save ChildS Pro): an international, multicentre, prospective registry study.

BACKGROUND: Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke. METHODS: In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular thrombectomy plus best medical practice or best medical treatment alone. Intravenous thrombolysis was considered part of best medical treatment and therefore permitted in both groups. The primary outcome was the difference in median modified Rankin Scale (mRS) score between baseline (pre-stroke) and 90 days (±10 days) post-stroke, assessed by the Wilcoxon rank test (α=0·05). Efficacy outcomes in the endovascular thrombectomy and best medical treatment groups were compared in sensitivity analyses using propensity score matching. The Save ChildS Pro study is registered at the German Clinical Trials Registry, DRKS00018960. FINDINGS: Between Jan 1, 2020, and Aug 31, 2023, of the 241 patients in the Save ChildS Pro registry, 208 were included in the analysis (115 [55%] boys and 93 [45%] girls). 117 patients underwent endovascular thrombectomy (median age 11 years [IQR 6-14]), and 91 patients received best medical treatment (6 years [3-12]; p<0·0001). The median Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score on admission was 14 (IQR 10-19) in the endovascular thrombectomy group and 9 (5-13) in the best medical treatment group (p<0·0001). Both treatment groups had a median pre-stroke mRS score of 0 (IQR 0-0) at baseline. The change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·020). One (1%) patient developed a symptomatic intracranial haemorrhage (this patient was in the endovascular thrombectomy group). Six (5%) patients in the endovascular thrombectomy group and four (5%) patients in the best medical treatment group had died by day 90 (p=0·89). After propensity score matching for age, sex, and PedNIHSS score at hospital admission (n=79 from each group), the change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·029). Regarding the primary outcome for patients with suspected focal cerebral arteriopathy, endovascular thrombectomy (n=18) and best medical treatment (n=33) showed no difference in 90-day median mRS scores (2 [IQR 1-3] vs 2 [1-4]; p=0·074). INTERPRETATION: Clinical centres tended to select children with more severe strokes (higher PedNIHSS score) for endovascular thrombectomy. Nevertheless, endovascular thrombectomy was associated with improved functional outcomes in paediatric patients with large-vessel or medium-vessel occlusions compared with best medical treatment. Future studies need to investigate whether the positive effect of endovascular thrombectomy is confined to older and more severely affected children. FUNDING: None.

Factors influencing the success and complications of intraosseous access in pediatric patients-a prospective nationwide surveillance study in Germany.

Background: Vascular access is essential for the efficient treatment of critically ill children, but it can be difficult to obtain. Our study was conducted to analyze the feasibility and short-term safety of intraosseous access (IO) use as well as factors influencing its success and the incidence of complications in pediatric emergencies and resuscitation. This dataset of systematically documented intraosseous access attempts constitutes one of the largest published in the literature. Methods: Two-year nationwide prospective surveillance study in Germany from July 2017 to June 2019. Pediatric hospitals anonymously reported the case data of all children aged 28 days to 18 years who arrived with or were treated with an intraosseous access to the German Pediatric Surveillance Unit (GPSU). The main outcomes were the occurrence of complications, overall success and success at the first attempt. The influence of individual factors on outcomes was evaluated using multivariate regression models. Results: A total of 417 patients underwent 549 intraosseous access attempts. The overall rates of success and success at the first attempt were 98.3% and 81.9%, respectively. Approximately 63.6% of patients were successfully punctured within 3 min from the time of indication. Approximately 47.7% of IO access attempts required patient resuscitation. Dislocation [OR 17.74 (5.32, 59.15)] and other complications [OR 9.29 (2.65, 32.55)] occurred more frequently in the prehospital environment. A total of 22.7% of patients experienced minor complications, while 2.5% of patients experienced potentially severe complications. Conclusion: We conclude that intraosseous access is a commonly used method for establishing emergency vascular access in children, being associated with a low (age-dependent) rate of severe complications and providing mostly reliable vascular access despite a relatively high rate of dislocation.