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ZusammenfassungWir berichten über den geburtshilflichen und neonatologischen Verlauf einer 34-jährigen Geminigravida, die sich erstmalig in der 16+1 Schwangerschaftswoche (SSW) in unserer Klinik mit vorzeitigem Blasensprung vorstellte. Bei vitalen und zeitgerecht entwickelten Gemini mit Anhydramnion des führenden Zwillings erfolgte die stationäre Überwachung unter intravenöser antiinfektiver Therapie. Nach verhaltenem Abort des ersten Geminus in der 19+1 SSW wurde eine operative Intervention mit assistierter Entbindung des ersten Geminus unter Belassung der Plazenta in situ mit anschließendem notfallmäßigem totalen Muttermundverschluss durchgeführt. Die verbliebene Einzelschwangerschaft konnte bis zur 24. SSW fortgeführt werden. Dann erfolgte bei unaufhaltsamer Wehentätigkeit, vorzeitigem Blasensprung und steigenden Entzündungszeichen im Labor der Mutter die eilige Sectio. Postnatal zeigte das Frühgeborene einen für das Gestationsalter insgesamt erfreulichen Verlauf, so dass in zukünftigen ähnlichen Fällen die Option der operativen Maßnahmen mit berücksichtigt werden sollte.

Objective This study aimed to measure health-related quality of life (HRQOL) in children and adolescents with tuberous sclerosis complex (TSC) and quality of life (QOL) and depressive symptoms among caregivers. Methods Adequate metrics were used to assess HRQOL in children and adolescents with TSC (4-18 years, KINDLR) as well as QOL (EQ-5D) and symptoms of depression (BDI-II) among caregivers. Predictors for reduced HRQOL and depressive symptoms were identified by variance analysis, ordinal regression, and bivariate correlation. Results The mean HRQOL score was 67.9 ± 12.7, and significantly lower values were associated with increasing age, attending special needs education, TSC-associated psychiatric symptoms, and drug-related adverse events. The mean QOL of caregivers was 85.4 ± 15.7, and caregiver's sex, TSC mutation locus, familial TSC clustering, special needs education, degree of disability, care dependency, presence of TSC-associated psychiatric symptoms, and TSC severity were significant predictors of lower QOL. Depressive symptoms were identified in 45.7% of caregivers, associated with female sex of the caregiver, familial TSC clustering, special needs education, and presence of TSC-associated psychiatric symptoms of the child. Multivariate regression analysis revealed adolescence and drug-related adverse events as significant predictors for lower HRQOL in TSC children, and TSC2 variants predicted lower QOL and depressive symptoms in caregivers. Conclusion Compared with other chronic diseases, such as headache, diabetes or obesity, children with TSC have significantly lower HRQOL, which further decreases during adolescence. A decreased HRQOL of patients correlates with a lower QOL and increased symptoms of depression of their caregivers. These results may improve the comprehensive therapy and care of children and adolescents with TSC and their families and caregivers. Trial registration DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.

To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity.In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication.Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy.These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

Seizures are a primary and early disease manifestation of Tuberous Sclerosis Complex (TSC). We aimed to describe the age-stratified patterns of antiseizure drug (ASD) treatments among children, adolescents, and adults with TSC in Germany. Additionally, we reviewed real-world and clinical study evidence regarding ASD utilization in patients with TSC.We evaluated the pattern of routine ASD use and everolimus prescriptions based on a 2019 multicenter survey of 268 individuals with TSC-associated epilepsy. We contextualized the results with a structured review of real-world and clinical study evidence.TSC-associated epilepsy treatment comprises a wide variety of ASDs. In this German sample, the majority of patients were treated with polytherapy, and lamotrigine (34.7%), valproate (32.8%), oxcarbazepine (28.7%), vigabatrin (19.0%), and levetiracetam (17.9%) were identified as the most-commonly used ASDs. In addition, everolimus was used by 32.5% of patients. In adherence to current TSC guidelines, the disease-modifying ASD vigabatrin was widely used in children (58% below the age of 5 years), whereas treatment in adults did not necessarily reflect guideline preference for (partial) GABAergic ASDs.The selection of ASDs for patients with TSC-associated epilepsy follows well-evaluated recommendations, including the guidelines regarding vigabatrin use in children. Several characteristics, such as the comparatively high frequency of valproate use and polytherapy, reflect the severity of TSC-associated epilepsy.

Anogenital and oropharyngeal infections with human papilloma viruses (HPV) are common. Clinically manifest disease may significantly impact quality of life; the treatment of HPV-associated lesions is associated with a high rate of recurrence and invasive neoplasms, such as cervical, anal, vulvar, penile, and oropharyngeal cancers, which are characterized by significant morbidity and mortality. Vaccination against HPV is an effective and safe measure for the primary prevention of HPV-associated lesions, but immunization rates are still low in Germany. The present publication is an abridged version of the German evidence and consensus-based guideline "Vaccination recommendations for the prevention of HPV-associated lesions", which is available on the website of the German Association of the Scientific Medical Societies (AWMF). On the basis of a systematic review with meta-analyses, a representative panel developed and agreed upon recommendations for the vaccination of different populations against HPV. In addition, consensus-based recommendations were developed for specific issues relevant to everyday practice. Based on current evidence and a representative expert consensus, these recommendations are intended to provide guidance in a field in which there is often uncertainty and in which both patients and health care providers are sometimes confronted with controversial and emotionally charged points of view.

Das Tragen von Masken (Alltagsmaske oder chirurgische Maske) ist neben der Abstandswahrung und Hygienemasnahmen zu einem wesentlichen Mittel zur Eindammung der SARS-CoV-2-Pandemie geworden. Sie stellen eine wesentliche Barriere fur infektiose Tropfchen im Nahfeld dar und konnen neben dem Fremdschutz moglicherweise auch den Trager schutzen. Nach Darstellung moglicher korperlicher oder seelischer Nebenwirkungen bei Erwachsenen werden die wenigen Daten zu unerwunschten Wirkungen bei Kindern referiert. Bei bestimmungsgemaser Anwendung sind bislang keine wesentlichen Nebenwirkungen bekannt geworden. Allerdings konnen Masken sehr lastig sein. Die Schlussfolgerung besagt, dass bei gesunden wachen Kindern, die jederzeit in der Lage sind, die Maske selbststandig abzunehmen, unerwunschte Wirkungen nicht zu befurchten sind. Wahrend Kinder etwa ab 10 Jahren mit einer Maske nach altersgemaser Aufklarung und Demonstration sinnvoll und effektiv umgehen konnen, sodass das Tragen auch vorgeschrieben werden kann, sollten Grundschuler nicht dazu verpflichtet und Vorschulkinder davon befreit werden. Die Tragedauer sollte begrenzt werden, und Schulkinder, die an ihrem Platz unter Einhaltung des Abstandsgebotes sitzen, sollen die Maske abnehmen durfen.

Eine Besiedlung mit Kopflausen ist eine zumeist harmlose Parasitose des Menschen. Dennoch hat eine „Verlausung“ eine grose gesellschaftliche und soziale Bedeutung. Unsicherheiten in Bezug auf angemessenes Handeln und Behandeln, ein breiter Markt an uberwiegend verschreibungsfreien Therapeutika sowie Infektionsschutzregelungen fuhren nicht selten zu erheblichen familiaren Belastungen, zu hohen Kosten sowie zu Fehlzeiten in Kita, Schule und am Arbeitsplatz. Bei kritischer Durchsicht aktueller Handlungsempfehlungen internationaler Fachgesellschaften und Infektionsschutzbehorden wird deutlich, dass sich nicht alle dort aufgefuhrten Hinweise konsequent auf wissenschaftliche oder epidemiologische Erkenntnisse beziehen. Wesentliche Unterschiede ergeben sich zwischen diesen Expertisen nicht zuletzt in der Empfehlung einzusetzender Kopflaustherapeutika. Wahrend der Einsatz von Medikamenten v. a. durch nationale Zulassungsbeschrankungen begrenzt wird, unterliegen Medizinprodukte sowohl bei der Zulassung als auch beim therapeutischen Einsatz deutlich niedrigeren rechtlichen Hurden. Dies beeinflusst auch die Studienlage zur Wirksamkeit einzelner Mittel. Die Kommission fur Infektionskrankheiten und Impffragen der Deutschen Akademie fur Kinder- und Jugendmedizin e. V. (DAKJ) hat diese Gesamtsituation zum Anlass genommen, die Literatur zur Kontrolle von Kopflausbesiedlungen umfassend zu sichten und die belegten Evidenzen sowie plausibel belegten Erkenntnisse zusammengetragen. Hinweise zu Biologie, Epidemiologie und Ausbreitungsdynamik der Kopflaus sollen es der Arzteschaft und anderen Ratgebenden wie padagogischen und pharmazeutischen Fachkraften ermoglichen, Betroffene und vermeintlich Betroffene bestmoglich zu beraten. Mit dieser Stellungnahme mochten wir eine Ubersicht zu einem evidenzbasierten Umgang mit dieser Parasitose geben. Wir hoffen, dass durch die starkere Fokussierung auf wirksame Ansatze bei gleichzeitiger Vermeidung unwirksamer Empfehlungen letztendlich eine verbesserte Kontrolle dieser Gesundheitsbelastung und ihrer Folgen im Sinne eines sekundarpraventiven Ansatzes moglich ist.

ZUSAMMENFASSUNGInfektionen mit Neisseria meningitidis sind eine der Todesursachen bei Kindern jenseits der Neugeborenenperiode mit der höchsten Inzidenz bei Säuglingen unter 12 Monaten. Die Epidemiologie invasiver Meningokokken-Erkrankungen (IME) variiert regional und temporär sowie die auslösenden Serotypen (A, B, C, W, X und Y) betreffend. IME zeigen einen akuten Verlauf und bedeuten eine hohe Langzeitbelastung für jeden Einzelnen. Bis zu 10 % der Patienten sterben innerhalb der ersten 48 Stunden. Bei 10–20 % der Überlebenden finden sich Folgeschäden. Nach Einführung der Routine-MenC-Impfung bleiben MenB und WY ein ernstzunehmender Grund von IME. In Deutschland ist die Inzidenz von IMD insgesamt niedrig und abnehmend. Es sind zwei verschiedene MenB-Impfstoffe verfügbar. Beide basieren auf einer Multikomponenten-Proteinstruktur. Die MenC-Vakzine ist ein Konjugatimpfstoff.Streptococcus pneumoniae kolonisiert den menschlichen Nasopharynx. Abhängig vom Wirt und weiteren Faktoren können durch Pneumokokken invasive Erkrankungen (IPD), wie Meningitis, Sepsis und bakterielle Pneumonie, ausgelöst werden. Es sind zwei verschiedene Vakzin-Typen verfügbar, zum einen konjugierte und zum anderen ein unkonjugierter Impfstoff (Polysaccharidimpfstoff). Konjugierte Polysaccharid-Impfstoffe (PCV) sind in zwei verschiedenen Formulierungen verfügbar, 10- und 13-valent. Bei Erwachsenen kommt ein 23-valenter unkonjugierter Polysaccarid-Impfstoff zur Anwendung. Mehr als 30 Länder haben weltweit inzwischen im Rahmen nationaler Impfprogramme 7 den, 10- bzw. 13-valenten PCV eingeführt. Es sind eine hohe Wirksamkeit und Effektivität unter den geimpften als auch ungeimpften Kindern und Erwachsenen nachweisbar. Allerdings ist auch ein Anstieg der IPD zu beobachten, welche durch Serotypen verursacht werden, die nicht im Impfstoff enthalten sind. Dieses Phänomen wird „Replacement” genannt.

Diese Leitlinie richtet sich an Dermatologen, Ophthalmologen, HNO-Arzte, Padiater, Neurologen, Virologen sowie Infektiologen, Anasthesisten und Allgemeinmediziner in Klinik und Praxis und dient zur Information fur andere medizinische Fachrichtungen, die an der Behandlung des Zoster beteiligt sind. Daruber hinaus soll die Leitlinie Kostentragern und politischen Entscheidungstragern zur Orientierung dienen. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen, Virologen/Infektiologen, Ophthalmologen, HNO-Arzten, Neurologen, Padiatern und Anasthesisten/Schmerzmedizinern erstellt. Die Leitlinie stellt einen Uberblick uber die klinische und molekulare Diagnostik sowie den Antigennachweis, die Antikorperkultur und Viruskultur dar. Diagnostisch besondere Situationen und komplizierte Verlaufe der Erkrankung finden ebenfalls Berucksichtigung. Die antivirale Therapie des Zoster und der Postzosterneuralgie wird im Allgemeinen und fur besondere Situationen dargelegt. Detaillierte Angaben zur Schmerzbehandlung finden Erwahnung und sind in einer Ubersicht dargestellt. Ebenso werden die lokaltherapeutischen Masnahmen thematisiert.

Invasive meningococcal disease (IMD) is a life-threatening, unpredictable condition. Vaccines are available against 5 of the 6 meningococcal serogroups (Men) accounting for nearly all IMD cases worldwide; conjugate monovalent MenC, quadrivalent MenACWY, and protein-based MenB vaccines are commonly used. We provide a comprehensive overview of the evolution of meningococcal vaccination strategies employed in national immunization programmes (NIPs) and their impact on IMD incidence in Europe. A more in-depth description is given for several countries: the United Kingdom (UK), the Netherlands, Greece, Italy, and Ireland. We searched European health authorities��� websites and PubMed. Various vaccines and immunization schedules are used in 21 NIPs. Most countries implement MenC vaccination in infants, MenACWY in adolescents, and a growing number, MenB in infants. Only Malta has introduced MenACWY vaccination in infants, and several countries reimburse immunization of toddlers. The UK, Italy, Ireland, Malta, Andorra, and San Marino recommend MenB vaccination in infants and MenACWY vaccination in adolescents, targeting the most prevalent serogroups in the most impacted age groups. Main factors determining new vaccination strategies are fluctuating IMD epidemiology, ease of vaccine implementation, ability to induce herd protection, favorable benefit���risk balance, and acceptable cost-effectiveness. Since 1999, when the UK introduced MenC vaccination, the reduction in IMD incidence has been gradually enhanced as other countries adopted routine meningococcal vaccinations. Meningococcal vaccination strategies in each country are continually adapted to regional epidemiology and national healthcare priorities. Future strategies may include broader coverage vaccines when available (e.g., MenABCWY, MenACWY), depending on prevailing epidemiology.

Children have a high burden of influenza and play a central role in spreading influenza. Routinely vaccinating children against influenza may, thus, not only reduce their disease burden, but also that of the general population, including the elderly who frequently suffer severe complications. Using the published individual-based tool 4Flu, we simulated how pediatric vaccination would change infection incidence in Germany. Transmission of four influenza strains was simulated in 100,000 individuals with German demography and contact structure. After initialization with the recorded trivalent influenza vaccination coverage for 20 years (1997–2016), all vaccinations were switched to quadrivalent influenza vaccine (QIV). Scenarios where vaccination coverage of children (0.5-17-year-old) was increased from the current value (4.3%) to a maximum of 10-60% were compared to baseline with unchanged coverage, averaging results of 1,000 pairs of simulations over a 20-year evaluation period (2017–2036). Pediatric vaccination coverage of 10-60% annually prevented 218–1,732 (6.3–50.5%) infections in children, 204–1,961 (2.9–28.2%) in young adults and 95–868 (3.1–28.9%) in the elderly in a population of 100,000 inhabitants; overall, 34.1% of infections in the total population (3.7 million infections per year in Germany) can be prevented if 60% of all children are vaccinated annually. 4.4–4.6 vaccinations were needed to prevent one infection among children; 1.7–1.8 were needed to prevent one in the population. Enhanced pediatric vaccination prevents many infections in children and even more in young adults and the elderly.

This current consensus paper for long COVID complements the existing AWMF S1 guidelines for long COVID with a detailed overview on the various clinical aspects of long COVID in children and adolescents. Members of 19 different pediatric societies of the DGKJ convent and collaborating societies together provide expert-based recommendations for the clinical management of long COVID based on the currently available but limited academic evidence for long COVID in children and adolescents. It contains screening questions for long COVID and suggestions for a structured, standardized pediatric medical history and diagnostic evaluation for patients with suspected long COVID. A time and resource-saving questionnaire, which takes the clinical complexity of long COVID into account, is offered via the DGKJ and DGPI websites as well as additional questionnaires suggested for an advanced screening of specific neurocognitive and/or psychiatric symptoms including post-exertional malaise (PEM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). According to the individual medical history as well as clinical signs and symptoms a step by step diagnostic procedure and a multidisciplinary therapeutic approach are recommended.

Simple Summary Medulloblastoma is the most common malignant childhood brain tumor and it is considered poor immunogenic because of its low mutational burden. Nevertheless, several clinical trials are currently evaluating immunotherapy for medulloblastoma patients, since new treatment strategies for this entity are a matter of utmost urgency. Tumor specific antigens resulting from gene fusions are potentially highly immunogenic. In our study, we identified a new medulloblastoma-specific fusion transcript EPC2-GULP1.The resulting protein sequence produced a neoantigen, which was able to activate CD8+ T cells. Thus, our data indicate an immunotherapeutic approach for pediatric medulloblastoma patients carrying the EPC2-GULP1 fusion or other fusions generating immunogenic neoantigens. Abstract Medulloblastoma is the most common malignant brain tumor in children. Immunotherapy is yet to demonstrate dramatic results in medulloblastoma, one reason being the low rate of mutations creating new antigens in this entity. In tumors with low mutational burden, gene fusions may represent a source of tumor-specific neoantigens. Here, we reviewed the landscape of fusions in medulloblastoma and analyzed their predicted immunogenicity. Furthermore, we described a new in-frame fusion protein identified by RNA-Seq. The fusion involved two genes on chromosome 2 coding for the enhancer of polycomb homolog 2 (EPC2) and GULP PTB domain containing engulfment adaptor 1 (GULP1) respectively. By qRT-PCR analysis, the fusion was detected in 3 out of 11 medulloblastoma samples, whereby 2 samples were from the same patients obtained at 2 different time points (initial diagnosis and relapse), but not in other pediatric brain tumor entities. Cloning of the full-length sequence indicated that the fusion protein contains the N-terminal enhancer of polycomb-like domain A (EPcA) of EPC2 and the coiled-coil domain of GULP1. In silico analyses predicted binding of the neoantigen-derived peptide to HLA-A*0201. A total of 50% of the fusions described in the literature were also predicted to produce an immunogenic peptide. The EPC2-GULP1 fusion peptide was able to induce a de novo T cell response characterized by interferon gamma release of CD8+ cytotoxic T cells in vitro. While the functional relevance of this fusion in medulloblastoma biology remains to be clarified, our data support an immunotherapeutic approach for pediatric medulloblastoma patients carrying the EPC2-GULP1 fusion and other immunogenic fusions.

Background The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder. Objective The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient’s perspective. Methods A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC. Results Of 365 participants, 36.7% (n = 134) reported the current or past intake of EVE, including 31.5% (n = 115) who were taking EVE at study entry. The mean EVE dosage was 6.1 ± 2.9 mg/m2 (median: 5.6 mg/m2, range 2.0–15.1 mg/m2) in children and adolescents and 4 ± 2.1 mg/m2 (median: 3.7 mg/m2, range 0.8–10.1 mg/m2) in adult patients. An early diagnosis of TSC, the presence of angiomyolipoma, drug-refractory epilepsy, neuropsychiatric manifestations, subependymal giant cell astrocytoma, cardiac rhabdomyoma and overall multi-organ involvement were associated with the use of EVE as a disease-modifying treatment. The reported efficacy was 64.0% for angiomyolipoma (75% in adult patients), 66.2% for drug-refractory epilepsy, and 54.4% for subependymal giant cell astrocytoma. The overall retention rate for EVE was 85.8%. The retention rates after 12 months of EVE therapy were higher among adults (93.7%) than among children and adolescents (88.7%; 90.5% vs 77.4% after 24 months; 87.3% vs 77.4% after 36 months). Tolerability was acceptable, with 70.9% of patients overall reporting adverse events, including stomatitis (47.0%), acne-like rash (7.7%), increased susceptibility to common infections and lymphoedema (each 6.0%), which were the most frequently reported symptoms. With a total score of 41.7 compared with 36.8 among patients not taking EVE, patients currently being treated with EVE showed an increased Liverpool Adverse Event Profile. Noticeable deviations in the sub-items ‘tiredness’, ‘skin problems’ and ‘mouth/gum problems’, which are likely related to EVE-typical adverse effects, were more frequently reported among patients taking EVE. Conclusions From the patients’ perspective, EVE is an effective and relatively well-tolerated disease-modifying treatment option for children, adolescents and adults with TSC, associated with a high long-term retention rate that can be individually considered for each patient. Everolimus therapy should ideally be supervised by a centre experienced in the use of mechanistic target of rapamycin inhibitors, and adverse effects should be monitored on a regular basis.

Objectives Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies showed a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. Methods This prospective, multicentre cohort study titled “AutoPilot-Dx”, aimed to validate signature performance and estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data. Results In total, 1140 patients were recruited (2/2017–12/2018), of which 1008 met eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with sensitivity of 93.7% (95% CI, 88.7–98.7), specificity of 94.2% (92.2–96.1), positive predictive value of 73.0% (65.0–81.0), negative predictive value of 98.9% (98.0–99.8), and 9.8% equivocal test results. The signature performed consistently across different patient subgroups and detected bacterial immune response in viral PCR positive patients. Conclusions The findings validate high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort and support its potential to reduce antibiotic overuse in children with viral infections. Trial registration Clinicaltrials.gov identifier: NCT03052088.

Background Tuberous sclerosis complex (TSC) is a monogenetic, multisystemic disease characterised by the formation of benign tumours that can affect almost all organs, caused by pathogenic variations in TSC1 or TSC2. In this multicentre study from Germany, we investigated the influence of sociodemographic, clinical, and therapeutic factors on quality of life (QoL) among individuals with TSC. Methods We assessed sociodemographic and clinical characteristics and QoL among adults with TSC throughout Germany using a validated, three-month, retrospective questionnaire. We examined predictors of health-related QoL (HRQoL) using multiple linear regression analysis and compared the QoL among patients with TSC with QoL among patients with other chronic neurological disorders. Results We enrolled 121 adults with TSC (mean age: 31.0 ± 10.5 years; range: 18–61 years, 45.5% [n = 55] women). Unemployment, a higher grade of disability, a higher number of organ manifestations, the presence of neuropsychiatric manifestations or active epilepsy, and a higher burden of therapy-related adverse events were associated with worse QoL, as measured by two QoL instruments (EuroQoL-5 dimensions [EQ-5D] and Quality of Life in Epilepsy Patients [QOLIE-31]). Neuropsychiatric and structural nervous system manifestations, the number of affected organs, and therapy-related adverse events were also associated with higher depression, as measured by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). In multiple regression analysis, more severe therapy-related adverse events (large effect, p p p = 0.003) were independently associated with worse HRQoL, explaining 65% of the variance (p p Conclusions Active epilepsy, neuropsychiatric manifestations (such as anxiety and depression), and therapy-related adverse events are important independent predictors of worse quality of life among adults with TSC. Generic quality of life in TSC with several manifestations is similar to uncontrolled severe chronic diseases and significantly negatively correlates with TSC severity. Trial registration DRKS, DRKS00016045. Registered 01 March 2019.

Protection by meningococcal group A, C, W and Y (MenACWY) vaccines against four meningococcal disease-causing serogroups is increasingly important because of changing epidemiologic patterns of meningococcal disease, including recent meningococcal serogroup W outbreaks/disease clusters. The MenACWY vaccine conjugated to tetanus toxoid (MenACWY-TT) has been extensively evaluated across the age spectrum (age ≥6 weeks) in randomized Phase II and III and in postmarketing studies. Results support the robust immunogenicity of MenACWY-TT across ages and coadministration with other vaccines. The safety profile is similar regardless of age, primary versus booster vaccination, or concomitant administration; local (swelling, pain, redness) and systemic (fever, fatigue, headache, drowsiness, loss of appetite, irritability) reactogenicity events are most common. These data support use of MenACWY-TT to protect against MenACWY disease.

Background Value assessment of vaccination programs against serogroup B invasive meningococcal disease (IMD) is on the agenda of public health authorities. Current evidence on the burden due to IMD is unfit for pinning down the nature and magnitude of the full social and economic costs of IMD for two reasons. First, the concepts and components that need to be studied are not agreed, and second, measures of the concepts that have been studied are weak and inconsistent. Thus, the economic evaluation of the available serogroup B meningococcal (MenB) vaccines is difficult. The aims of this DELPHI study are to: (1) agree on the concepts and components determining the burden of MenB diseases that need to be studied; and (2) seek consensus on appropriate methods and study designs to measure quality of life (QoL) associated with MenB induced long-term sequelae in future studies. Methods We designed a DELPHI questionnaire based on the findings of a recent systematic review on the QoL associated with IMD-induced long-term sequelae, and iteratively interviewed a panel of international experts, including physicians, health economists, and patient representatives. Experts were provided with a controlled feedback based on the results of the previous round. Results Experts reached consensus on all questions after two DELPHI rounds. Major gaps in the literature relate (i) to the classification of sequelae, which allows differentiation of severity levels, (ii) to the choice of QoL measures, and (iii) to appropriate data sources to examine long-term changes and deficits in patients’ QoL. Conclusions Better conceptualisation of the structure of IMD-specific sequelae and of how their diverse forms of severity might impact the QoL of survivors of IMD as well as their family network and care-providers is needed to generate relevant, reliable and generalisable data on QoL in the future. The results of this DELPHI panel provide useful guidance on how to choose the study design, target population and appropriate QoL measures for future research and hence, help promote the appropriateness and consistency in study methodology and sample characteristics. Electronic supplementary material The online version of this article (10.1186/s12955-019-1159-0) contains supplementary material, which is available to authorized users.

Anhand von 2 Kasuistiken werden die Ernsthaftigkeit und Gefahr einer Bordetella-pertussis-Infektion bei jungen Sauglingen beschrieben. Bei beiden Kindern handelte es sich um einen komplizierten Krankheitsverlauf mit einer Hyperleukozytose. Die Hyperleukozytose stellt eine seltene, jedoch sehr ernst zu nehmende Komplikation dar, der ggf. fruhzeitig durch eine Austauschtransfusion zu begegnen ist. Der Pathomechanismus ist nicht endgultig geklart; Ausloser scheint das zirkulierende Pertussistoxin zu sein.

Ein 10 Monate alter Saugling wird vom Notarzt in unsere Klinik gebracht. Das Kind ist bewusstlos und intubiert. Angeblich ist es vom Sofa auf den Boden gefallen. Jedoch lassen die Angaben des Vaters Zweifel aufkommen.

Background Three hexavalent vaccines against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib) are licensed in Europe: Infanrix hexa (DT3aP-HBV-IPV/Hib), Hexyon (DT2aP-HBV-IPV-Hib) and Vaxelis (DT5aP-HBV-IPV-Hib). Methods A systematic literature search was performed in various electronic databases to identify published peer-reviewed head-to-head studies comparing any licensed hexavalent vaccine to another. Results Predefined inclusion criteria were met by 12 articles. Individual studies concluded that the 3 hexavalent vaccines have acceptable safety profiles although some significant differences were observed in their reactogenicity profiles. The immunogenicity of DT2aP-HBV-IPV-Hib and DT5aP-HBV-IPV-Hib was non-inferior versus DT3aP-HBV-IPV/Hib. Some differences in immune responses to common antigens were observed, but their clinical relevance was not established. Anti-filamentous hemagglutinin (FHA) from pertussis and anti-polyribosylribitol phosphate (PRP) from Hib antibody concentrations tended to be higher, and anti-HBV and anti-pertussis toxin (PT) from pertussis antibody concentrations lower in DT2aP-HBV-IPV-Hib versus DT3aP-HBV-IPV/Hib vaccinees. Anti-PT and post-primary anti-PRP antibody concentrations tended to be higher, and anti-HBV, anti-FHA, anti-pertactin from pertussis and post-booster anti-PRP antibody concentrations lower in DT5aP-HBV-IPV-Hib versus DT3aP-HBV-IPV/Hib recipients. Slightly lower immune responses towards most vaccine antigens were observed with 2 + 1 versus 3 + 1 schedules post-primary vaccination, suggesting that 2 + 1 schedules should only be considered in countries with very high vaccination coverage. Conclusion Although the licensed hexavalent vaccines are generally considered similar, analyses of immunogenicity data from head-to-head trials highlighted differences that could be related to differences in composition and formulation. In addition, the demonstrated non-inferiority of the immunogenicity of the more recent vaccines versus DT3aP-HBV-IPV/Hib does not allow a full bridging to similar efficacy, effectiveness and safety. The availability of DT3aP-HBV-IPV/Hib over > 20 years allowed to collect a wealth of data on its long-term immunogenicity, safety and effectiveness in clinical and post-marketing studies, and makes it a key pillar of pediatric immunization.

Introduction: The hexavalent vaccine DT3aP-HBV-IPV-Hib (Infanrix hexa, GSK) was first licensed in Europe in 2000. DT2aP-HBV-IPV-Hib (Hexyon/Hexacima/Hexaxim, Sanofi Pasteur), and DT5aP-HBV-IPV-Hib (Vaxelis, MCM Vaccine Company) were licensed in the EU in 2013 and 2016, respectively, based largely on studies demonstrating non-inferiority to DT3aP-HBV-IPV-Hib for immunogenicity and comparable reactogenicity profiles. Methods: We conducted a systematic literature review looking for direct head-to-head trials comparing DT2aP-HBV-IPV-Hib and DT5aP-HBV-IPV-Hib with DT3aP-HBV-IPV-Hib. The incidence of solicited local and systemic reactions following primary series administration of DT3aP-HBV-IPV-Hib or DT2aP-HBV-IPV-Hib were meta-analyzed. Results: A total of 317 unique records were retrieved from the search; nine met the predefined inclusion criteria; seven reported studies comparing DT3aP-HBV-IPV-Hib and DT2aP-HBV-IPV-Hib. Six trials assessing outcomes of the primary vaccination series were identified. Odds ratios and 95% confidence intervals (OR; 95%CI) were computed for DT3aP-HBV-IPV-Hib, using DT2aP-HBV-IPV-Hib as reference, for redness (0.72; 0.63–0.83), pain (0.74; 0.62–0.89), swelling (0.86; 0.74–0.99) at injection site, fever (0.67; 0.54–0.83), persistent crying (0.72; 0.61–0.84), drowsiness (0.82; 0.71–0.94), irritability (0.82; 0.69–0.98), anorexia (0.83; 0.72–0.95), and vomiting (0.96; 0.83–1.11). Conclusion: ORs of analyzed local and systemic solicited adverse reactions after primary vaccination with DT3aP-HBV-IPV-Hib appear to be slightly lower than with DT2aP-HBV-IPV-Hib.

Many countries are replacing meningococcal serogroup C (MenC) conjugate vaccines (MCCV) with quadrivalent conjugate (MenACWY) vaccines, such as MenACWY-TT (Nimenrix®). This review examined eight studies comparing MenC immune responses induced by MenACWY-TT and MCCV to determine if these data support these changes. MenC serum bactericidal antibody levels using human (hSBA) or rabbit complement (rSBA) were evaluated at ~1 month postvaccination. Overall, ≥98.4% of infants administered 2 + 1 MenACWY-TT or MCCV schedules had rSBA titers ≥1:8 postprimary and postbooster vaccination; hSBA titers ≥1:8 were similar. In toddlers administered single MenACWY-TT or MCCV doses, ≥97.3% had rSBA titers ≥1:8 postvaccination; percentages with hSBA titers ≥1:8 were higher post-MenACWY-TT. Of children and adolescents receiving primary and booster MenACWY-TT and MCCV, ≥98.6% had rSBA titers ≥1:8; all children receiving MenACWY-TT or MCCV booster had hSBA titers ≥1:8 postdosing. MenC immune responses induced by MenACWY-TT are robust and generally comparable/superior to MCCV, supporting changes to recommendations.

Das Tragen von Masken (Alltagsmaske oder chirurgische Maske) ist neben der Abstandswahrung und Hygienemaßnahmen zu einem wesentlichen Mittel zur Eindämmung der SARS-CoV-2-Pandemie geworden. Sie stellen eine wesentliche Barriere für infektiöse Tröpfchen im Nahfeld dar und können neben dem Fremdschutz möglicherweise auch den Träger schützen. Nach Darstellung möglicher körperlicher oder seelischer Nebenwirkungen bei Erwachsenen werden die wenigen Daten zu unerwünschten Wirkungen bei Kindern referiert. Bei bestimmungsgemäßer Anwendung sind bislang keine wesentlichen Nebenwirkungen bekannt geworden. Allerdings können Masken sehr lästig sein. Die Schlussfolgerung besagt, dass bei gesunden wachen Kindern, die jederzeit in der Lage sind, die Maske selbstständig abzunehmen, unerwünschte Wirkungen nicht zu befürchten sind. Während Kinder etwa ab 10 Jahren mit einer Maske nach altersgemäßer Aufklärung und Demonstration sinnvoll und effektiv umgehen können, sodass das Tragen auch vorgeschrieben werden kann, sollten Grundschüler nicht dazu verpflichtet und Vorschulkinder davon befreit werden. Die Tragedauer sollte begrenzt werden, und Schulkinder, die an ihrem Platz unter Einhaltung des Abstandsgebotes sitzen, sollen die Maske abnehmen dürfen.

Diese Leitlinie richtet sich an Dermatologen, Ophthalmologen, HNO-Ärzte, Pädiater, Neurologen, Virologen sowie Infektiologen, Anästhesisten und Allgemeinmediziner in Klinik und Praxis und dient zur Information für andere medizinische Fachrichtungen, die an der Behandlung des Zoster beteiligt sind. Darüber hinaus soll die Leitlinie Kostenträgern und politischen Entscheidungsträgern zur Orientierung dienen. Die Leitlinie wurde im formellen Konsensusverfahren (S2k) von Dermatologen, Virologen/Infektiologen, Ophthalmologen, HNO-Ärzten, Neurologen, Pädiatern und Anästhesisten/Schmerzmedizinern erstellt. Die Leitlinie stellt einen Überblick über die klinische und molekulare Diagnostik sowie den Antigennachweis, die Antikörperkultur und Viruskultur dar. Diagnostisch besondere Situationen und komplizierte Verläufe der Erkrankung finden ebenfalls Berücksichtigung. Die antivirale Therapie des Zoster und der Postzosterneuralgie wird im Allgemeinen und für besondere Situationen dargelegt. Detaillierte Angaben zur Schmerzbehandlung finden Erwähnung und sind in einer Übersicht dargestellt. Ebenso werden die lokaltherapeutischen Maßnahmen thematisiert.

The present guidelines are aimed at residents and board-certified specialists in the fields of dermatology, ophthalmology, ENT, pediatrics, neurology, virology, infectious diseases, anesthesiology, general medicine and any other medical specialties involved in the management of patients with herpes zoster. They are also intended as a guide for policymakers and health insurance funds. The guidelines were developed by dermatologists, virologists, ophthalmologists, ENT physicians, neurologists, pediatricians and anesthesiologists/pain specialists using a formal consensus process (S2k). Readers are provided with an overview of the clinical and molecular diagnostic workup, including antigen detection, antibody tests and viral culture. Special diagnostic situations and complicated disease courses are discussed. The authors address general and special aspects of antiviral therapy for herpes zoster and postherpetic neuralgia. Furthermore, the guidelines provide detailed information on pain management including a schematic overview, and they conclude with a discussion of topical treatment options.