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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.To explore the potential use of electronic tools to improve the delivery of GT under real-world conditions.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.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.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.

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.

Prophylaxis treatment is the current standard of care for patients with severe hemophilia. Factor concentrates with improved pharmacokinetics have offered more options for individualizing treatment. The treatment focus may be on increased protection, aiming for higher trough factor levels or longer dosing intervals to reduce the burden of hemophilia. Both aspects can have long-term effects on joint health. Products, such as rVIII‑SingleChain and rIX-FP have been developed to reduce the treatment burden for patients with hemophilia and optimize prophylactic efficacy. The objective of this report is to provide a summary of the clinical experience of different Hemophilia Treatment Centers in managing the switch to rVIII-SingleChain or rIX-FP in patients with hemophilia.This report summarizes a selection of patient cases presented at the 3rd Alliance for Coagulation Academy Meeting in October 2020. The cases from the participating centers provide examples of the clinical experience in managing patients' switch to rVIII-SingleChain and rIX‑FP, including which types of patients are suitable for switching, and practical steps in managing a switch.It is important to take into consideration the physical and social fulfillment of the patient when deciding to switch to rVIII-SingleChain or rIX-FP. The physician plays an important role in the motivation of patients as they understand not only the patient's needs but the potential benefits of the new treatment.The selected patient cases reported here demonstrate that patients may wish to switch factor products for a variety of reasons; therefore, it is critical to understand why patients switch and what they expect from switching.

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.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.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.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.Chronische Erkrankungen, wie z. B. angeborene Blutungsneigungen (IBD: Inherited Bleeding Disorders), gehen häufig mit einem erhöhten Versorgungsaufwand einher. Maßnahmen zur Eindämmung der COVID-19 Pandemie, inklusive Isolation und Triageierung, haben zu Einschränkungen in der Krankenversorgung von chronisch kranken Patienten geführt. Ziel der vorliegenden Arbeit ist es, die Auswirkungen der COVID-19 Pandemie auf die Krankenversorgung von IBD-Patienten zu untersuchen.In dieser multizentrischen Querschnittsstudie zur Bewertung der Auswirkungen von COVID-19 auf die psychische Gesundheit und Versorgungsqualität von Patienten mit angeborener Blutungsneigung wurde ein ad-hoc Fragebogen an 586 Patienten/Eltern von Kindern mit Hämophilie A, B oder von Willebrand Syndrom Typ 3 verschickt. Neben demografischen und klinischen Daten wurden IBD Patienten zu ihren Gedanken, Sorgen und Erfahrungen in Bezug auf ihre medizinische Versorgung während der COVID-19 Pandemie befragt. Unterschiede zwischen klinischen Subgruppen wurden berechnet.Signifikante Unterschiede zeigten sich zwischen Subgruppen (Schweregrad, Art der Therapie, Produktklasse, Komorbiditäten) bezüglich Übertragung von COVID-19 durch Plasmaprodukte, Auswirkungen COVID-19 positiver Testergebnisse, Angst COVID-19 zu bekommen, verzögerter Medikamentenversorgung und Physiotherapiebehandlung.Die medizinische Versorgung von IBD-Patienten, die eine kontinuierliche Versorgung mit lebensnotwendigen Medikamenten benötigen, stellt in Pandemiezeiten eine besondere Herausforderung dar. Daher sollten Sorgen und Ängste von IBD-Patienten ernst genommen und innovative Kommunikationswege zur Aufrechterhaltung von Therapiestandards und Versorgungsqualität etabliert werden.

Childhood arterial ischemic stroke differs in essential aspects from adult stroke. It is rare, often relatively unknown among laypersons and physicians and the wide variety of age-specific differential diagnoses (stroke mimics) as well as less established care structures often lead to a considerable delay in the diagnosis of stroke. The possible treatment options in childhood are mostly off-label. Experiences in well-established acute treatment modalities in adult stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in children and only based on case reports and case series. The etiological clarification is time-consuming due to the multitude of risk factors which must be considered. Identifying each child's individual risk profile is mandatory for acute treatment and secondary prevention strategies and has an influence on the individual outcome. In addition to the clinical neurological outcome the residual neurological effects of stroke on cognition and behavior are decisive for the integration of the child into its educational, later professional and social environment.

Childhood arterial ischaemic stroke (AIS) is a rare, but potentially life-threatening event which requires early diagnosis and adequate treatment. The reported significant time delay to childhood AIS diagnosis may be associated with low awareness, the more nonspecific clinical presentation as well as difficult clinical differentiation to more common "stroke mimics" and a less established "acute care structure" with delayed access to proper neuroimaging. Compared with adult stroke care, experiences with acute reperfusion therapies like thrombolysis and mechanical thrombectomy are promising but limited and not based on clinical trials. The etiological work-up is absolutely essential, as the child's individual risk profile determines acute management, secondary prevention, risk of recurrence and outcome. Follow-up care should be organized in a multidisciplinary setting covering all bio-psycho-social aspects to achieve the best integration of the child into its educational, later professional and social environments.Der Schlaganfall im Kindes- und Jugendalter ist ein seltenes, aber potentiell lebensbedrohliches Ereignis und erfordert rasche Diagnosestellung und Therapie. Aufgrund der geringen Awareness, der häufigen unspezifischen klinsichen Präsentation mit einer Fülle zu bedenkender, wahrscheinlicherer Differenzialdiagnosen sowie der noch wenig etablierten Versorgungsstrukturen wird der kindliche Schlaganfall oft erst mit einer deutlichen Zeitverzögerung diagnostiziert. In der Erwachsenenneurologie etablierte Revaskularisationstherapien können in der Pädiatrie aktuell nur als off-label Therapien mit begrenzten Erfahrungen eingesetzt werden. Die ätiologische Abklärung ist unabdingbar, bestimmt doch das individuelle Risikoprofil neben Akutmanagement und Rezidivprophylaxe auch das Rezidivrisiko und Outcome. Die Langzeitbetreuung der betroffenen Kinder und Jugendlichen sollte im multidisziplinären Setting unter Berücksichtigung aller bio-psycho-sozialer Aspekte erfolgen. Denn neben dem klinisch neurologischen Outcome sind insbesondere auch die Auswirkungen des Schlaganfalls auf Kognition und Verhalten für eine erfolgreiche Integration des Kindes in sein schulisches und soziales Umfeld mitentscheidend.

With the recent approval of improved therapeutic options for patients suffering from haemophilia A such as the extended half-life, recombinant factor concentrates, non-factor VIII replacement therapies like Emicizumab and after consideration of the currently running clinical trials investigating even more advanced approaches, counselling of parents of a newly diagnosed boy with haemophilia A has not become less demanding. Parents need to be informed about the pathophysiology, the chronic nature and the potential risks that are commonly associated with this disease and its treatment, depending on disease severity. Above all, the safety and efficacy of the medicinal drug(s) to be used are of utmost importance, given the impact of non-virus-inactivated plasma-derived factor concentrates in the 1980s. As a consequence, the subsequent development and registration of recombinant clotting factors from mammalian, and recently, even human, cell cultures are seen by many as a breakthrough, although, regarding the product-type-dependent development of inhibitors in previously untreated patients, the discussion is still open. Clinical data for the humanised bispecific antibody Emicizumab in paediatric patients below 2 years of age without inhibitors who suffer from severe haemophilia A are currently limited.Mit der Zulassung der halbwertszeitverlängerten, rekombinanten Faktorkonzentrate, der Zulassung des nicht auf Faktor VIII Substitution basierenden Emicizumab und unter Berücksichtigung der zurzeit laufenden klinischen Studien ist die Beratung der Eltern eines Jungen mit neu diagnostizierter Hämophilie A nicht einfacher geworden. Die Eltern sollten über die Pathophysiologie der Erkrankung und - unter Berücksichtigung der Schwere der Erkrankung - die damit und mit der Behandlung verbundenen Risiken und den chronischen Verlauf informiert werden. Die Sicherheit und Wirksamkeit des zur Behandlung ausgewählten Medikaments ist von allergrößter Bedeutung, vor allem unter Berücksichtigung der Auswirkungen der Gabe nicht virusinaktivierter, plasmatischer Faktorenkonzentrate in den 80-er Jahren. Die darauffolgende Entwicklung rekombinanter Faktorenkonzentrate aus Säugetierzelllinien (und kürzlich aus humanen Zelllinien) wird von vielen als Durchbruch angesehen. Inwieweit dies auch für die Behandlung zuvor unbehandelter Patienten zutrifft und inwiefern es die Entwicklung von Hemmkörpern beeinflusst, ist noch nicht abschließend geklärt. Die Menge an klinischen Daten für den humanisierten, bispezifischen Antikörper Emicizumab für pädiatrische Patienten unter 2 Jahren, die an schwerer Hämophilie A ohne Inhibitoren leiden, ist zurzeit noch begrenzt.

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.

Extracranial vascular malformations vary greatly and belong to the complex field of orphan diseases and can involve all segments of the vascular tree: arteries, capillaries, and veins, and similarly the lymphatic system. The classification according to the International Society for the Study of Vascular Anomalies (ISSVA) represents an important guidance for selecting appropriate therapy. Although many of the principles of endovascular treatment, including image-guided sclerotherapy and embolization, are similar in adult and pediatric practice, there are some distinct differences regarding the treatment of vascular malformations of children. Thus, it is crucial to involve longer-term plan about managing these chronic diseases and their impact on a growing child. This review provides a detailed overview over the clinical presentation of venous, lymphatic, and arteriovenous malformations in children and emphasizes the specifics of their interventional treatment options, including distinct pediatric dose limitations and procedure-related side effects.Extrakranielle vaskuläre Malformationen sind sehr variabel und gehören zum komplexen Feld der seltenen Erkrankungen. Sie können alle Segmente des Gefäßbaumes betreffen: Arterien, Kapillaren und Venen, sowie das Lymphgefäßsystem. Die Klassifizierung nach der International Society for the Study of Vascular Anomalies (ISSVA) stellt eine wichtige Orientierungshilfe für die adäquate Therapie dar. Obwohl viele der Prinzipien hinsichtlich der interventionellen Behandlung, wie der bildgesteuerten Sklerotherapie und Embolisation, im Grundsatz ähnlich zu denen erwachsener Patienten sind, gibt es einige deutliche Unterschiede bei der Behandlung von vaskulären Malformationen bei Kindern. Von entscheidender Bedeutung ist, die Behandlung dieser chronischen Erkrankungen und ihre Auswirkungen auf das heranwachsende Kind längerfristig zu betrachten. Diese Übersicht gibt einen detaillierten Überblick über die klinische Präsentation venöser, lymphatischer und arteriovenöser Malformationen bei Kindern und hebt die Besonderheiten der interventionellen Behandlungsoptionen hervor, einschließlich der spezifischen pädiatrischen Dosisbegrenzungen und therapieassoziierter Nebenwirkungen.

To evaluate real-world annualized bleeding rates (ABRs), dosing frequency, and factor consumption of four recombinant FVIII (rFVIII) products using pooled data from centers in the US, Germany, and Italy. De-identified patient medical chart data were collected from 48 hemophilia treatment centers in the US, Germany, and Italy. Patients included in this analysis had hemophilia A and were treated with rVIII-SingleChain, rFVIIIFc, octocog alfa, or BAY 81-8973 for ≥12 weeks. Where possible, patient selection considered age and disease severity in order to balance patient groups across products. Summary statistics were presented descriptively by product for dosing frequency, consumption, ABR/annualized spontaneous bleeding rate (AsBR), and corresponding percentage of patients with zero bleeds. Logistic regression was performed for patients with zero bleeds or zero spontaneous bleeds (vs. patients with any such bleeds). Generalized linear model regression was performed for ABR, AsBR, and consumption. All regression models included the product variable for comparison as well as additional independent variables for adjustment (age, weight, severity, and country for the consumption model, with the addition of consumption for the bleeding outcomes models). Overall, 616 patients were included (rVIII-SingleChain, n = 129; rFVIIIFc, n = 159; octocog alfa, n = 181; BAY 81-8973, n = 147). Dosing frequency was ≤2 times a week for 65.9%, 75.5%, 25.4%, and 40.1% of patients treated with rVIII-SingleChain, rFVIIIFc, octocog alfa, and BAY 81-8973, respectively. ABRs were not significantly different among products, with mean (median) values of 1.1 (0.0), 1.0 (0.0), 1.4 (1.0), and 1.9 (1.0) for rVIII-SingleChain, rFVIIIFc, octocog alfa, and BAY 81-8973, respectively. The percentage of patients with zero bleeds was comparable between rVIII-SingleChain and rFVIIIFc (59.7% vs. 62.3%; p =.916) and significantly higher for rVIII-SingleChain compared with octocog alfa (p p =.003). Comparison of mean weekly consumption showed: rVIII-SingleChain (83.0 IU/kg/week) vs. rFVIIIFc (96.9; p =.055) and significantly lower for rVIII-SingleChain vs. octocog alfa (108.6; p p =.001). The median values for weekly consumption were 85.7, 90.1, 100.1, and 98.5 IU/kg/week for rVIII-SingleChain, rFVIIIFc, octocog alfa, and BAY 91-8973, respectively. Similar trends were observed for all outcomes when analyzing the subgroups of patients aged ≥12 years and patients with severe disease (all age and ≥12 years). rVIII-SingleChain prophylaxis may provide improved bleed protection, less frequent dosing, and lower consumption compared with standard-acting FVIII products, and comparable protection and consumption to the other long-acting FVIII product, in patients with hemophilia A.

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.

Childhood arterial ischaemic stroke (AIS) is rare, but causes significant morbidity and mortality. We aimed to investigate incidence, age-dependent clinical presentation, and risk factors and to discuss the medical care situation in Germany. This prospective epidemiological study was conducted via ESPED (Erhebungseinheit fur Seltene Padiatrische Erkrankungen in Deutschland), a hospital-based German nation-wide surveillance unit for rare pediatric diseases. Children aged 28 days–18 years with first AIS between January 2015 and December 2017 were included. In the 3-year period, 164 children were reported. Incidence showed peaks in infants, children

Background Currently available coronavirus disease 2019 (COVID-19) vaccines are approved for intramuscular injection and efficacy may not be ensured when given subcutaneously. For years, subcutaneous vaccination was recommended in patients with hemophilia to avoid intramuscular bleeds. Therefore, recommendations for the application of COVID-19 vaccines are needed. Methods The Delphi methodology was used to develop consensus recommendations. An initial list of recommendations was prepared by a steering committee and evaluated by 39 hemophilia experts. Consensus was defined as ≥75% agreement and strong consensus as ≥95% agreement, and agreement as a score ≥7 on a scale of 1 to 9. After four rounds, a final list of statements was compiled. Recommendations Consensus was achieved that COVID-19 vaccines licensed only for intramuscular injection should be administered intramuscularly in hemophilia patients. Prophylactic factor replacement, given on the day of vaccination with a maximum interval between prophylaxis and vaccination of 24 hours (factor VIII and conventional factor IX concentrates) or 48 hours (half-life extended factor IX), should be provided in patients with moderate or severe hemophilia. Strong consensus was achieved that patients with mild hemophilia and residual factor activity greater than 10% with mild bleeding phenotype or patients on emicizumab usually do not need factor replacement before vaccination. Swelling, erythema, and hyperthermia after vaccination are not always signs of bleeding but should prompt consultation of a hemophilia care center. In case of injection-site hematoma, patients should receive replacement therapy until symptoms disappear. Conclusions Consensus was achieved on recommendations for intramuscular COVID-19 vaccination after replacement therapy for hemophilia patients depending on disease severity.

Objective Childhood acute ischemic stroke (CAIS) is a rare event. Diverse etiologies, risk factors, symptoms and stroke mimics hamper obtaining a fast diagnosis and implementing immediate recanalization strategies. Methods Over a period of 3 years (2015–2017), the data of 164 pediatric patients (> 28 days of life-18 years) with a first episode of AIS were submitted to a hospital-based nationwide surveillance system for rare disorders (ESPED). We report a subgroup analysis of patients who have undergone recanalization therapy and compare these data with those of the whole group. Results Twenty-eight patients (17%) with a median age of 12.2 years (range: 3.3–16.9) received recanalization therapy. Hemiparesis, facial weakness and speech disturbance were the main presenting symptoms. The time from onset of symptoms to confirmation of diagnosis was significantly shorter in the intervention group (4.1h vs. 20.4 h, p =

Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K&ndash, dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis.

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.

Patients suffering from haemophilia encounter various phases in life, in which individual needs, life situations, and self- and disease perception change rapidly. One of these phases spans from the beginning of puberty until early adulthood, in which individuals gain self-responsibility and reach independence and autonomy. In this challenging time that determines future health, adolescents and young adults need sustainable familiar and professional support. A change in health care team and treatment centre may expose adolescent patients to threats but also provides the possible opportunity to be well prepared. While there is emerging evidence that the so-called health care transition programmes are effective in maintaining quality of care in other disease areas, transition programmes for patients with haemophilia are still rare in Germany, and the evidence is limited. We describe the situation in Germany, discuss our experience in Munich and review some of the available guidance; we conclude that transition programmes should become a standard of care in haemophilia.Patienten mit Hämophilie durchlaufen verschiedene Lebensabschnitte, in denen sich ihre Bedürfnisse, Lebensumstände und ihr Blick auf die Erkrankung und sich selbst verändern. Eine dieser Phasen umfasst die Pubertät und den Übergang ins Erwachsenenalter. In dieser Zeit erlangen die Patienten Eigenverantwortung und streben nach Unabhängigkeit und Autonomie. Diese Phase ist herausfordernd und bestimmend für die gesundheitliche Zukunft. Daher benötigen die Patienten eine tragfähige familiäre und professionelle Unterstützung, um Ängsten zu begegnen und mögliche Chancen herauszuarbeiten. Die Effektivität von Transitions-Programmen wird bereits für viele Krankheitsbilder in der Literatur beschrieben, allerdings werden diese im Bereich der Hämophilie in Deutschland selten angewendet. Wir beschreiben die Situation in Deutschland, erläutern unsere Münchner Erfahrungen und besprechen einige der verfügbaren Empfehlungen aus der Literatur. Zusammenfassend sollten Transitions-Program Teil der Routinebehandlung bei Hämophilie werden.

Acute treatment of childhood arterial ischaemic stroke and prevention strategies for recurrent stroke episodes depend strongly on each child's individual risk profile. The aim of this study is to characterize risk factors for childhood stroke, their occurrence in isolation or combination, and to identify possible common risk factor patterns.This population-based study was conducted via ESPED, a surveillance unit for rare paediatric diseases in Germany. Children aged28days and18 years with an acute arterial ischaemic stroke occurring between January 2015 and December 2016 were included.Among 99 reported children with arterial ischaemic stroke, 56 children were male. Male predominance was significant in adolescents from 12 years old onward. Arterial ischaemic stroke was more common in very young children2 years of age and in adolescence. No risk factor was identified in 27 children. Hypercoagulable states (29%), cardiac disorders (24%), and arteriopathies (21%) were the most common risk factors. Some risk factor categories were more likely to be identified in isolation (i.e. cardiac disorders, prothrombotic abnormalities and chronic head and neck disorders) than others. The number of risk factors (n = 0-4) per patient and risk factor categories did not differ by age.Although we could not identify common patterns of risk factor combinations, several risk factors occurred more likely in isolation than others. Further research should focus on the impact of isolated presumed childhood stroke risk factors like certain prothrombotic abnormalities, migraine or a patent foramen ovale. With regard to different age groups, stroke mechanisms in male adolescents require particular attention.

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.

Der Schlaganfall bei Kinder und Jugendlichen tritt selten auf, ist aber immer ein kinderneurologischer Notfall. Fur das Outcome sind eine fruhzeitige Diagnostik und Therapieeinleitung, eine adaquate Rezidivpravention und speziell auf die Bedurfnisse jedes einzelnen Kindes und seine Entwicklung abgestimmte rehabilitative Masnahmen entscheidend.