Molekulare Epidemiologie von Vancomycin-resistenten Enterokokken am Universitätsklinikum Regensburg 2018 - 2019

Vancomycin-resistente Enterokokken gehören gemäß Infektionsschutzgesetz zu den in Deutschland zu erfassenden multiresistenten Erregern. In den letzten Jahrzehnten sind trotz präventiver Maßnahmen steigende VRE-Zahlen weltweit und insbesondere auch in Deutschland zu beobachten, sodass von einer hyperendemischen Situation gesprochen werden kann. Um dieser Entwicklung entgegen zu wirken und adäquate Schutzkonzepte für Patienten in Kliniken zu entwickeln ist ein besseres Verständnis der Transmissions¬wege notwendig. Ziel dieser Arbeit war es potenzielle Transmissionsereignisse und Risikobereiche am Universitätsklinikum Regensburg (UKR) aufzuzeigen sowie Einblicke in die Populations-struktur der im hospitalen Umfeld zirkulierenden Enterokokkenstämme auf Genomebene zu erhalten. Hierfür wurden in die Studie insgesamt 331 VRE-Patienten des UKR eingeschlossen und deren stationären Aufenthalte anhand einer Linelist über den Zeitraum eines Jahres hinweg dokumentiert und ausgewertet. Zudem erfolgte eine Erfassung der den Patien¬ten zugehörigen VRE-Isolate. Hierdurch ließen sich mögliche Transmissionen und insbesondere gehäuft auftretende Erstnachweise – als Hinweise für mögliche Ausbrüche – detektieren. Es konnte so eine Risikobeurteilung einzelner Stationen und Fachab¬teilungen erfolgen. Ergänzend hierzu erfolgte für ausgewählte Isolate aus Hochrisiko¬bereichen oder im Rahmen vermuteter Ausbrüche eine Gesamtgenomsequenzierung. Für die Genotypisierung wurde das Whole Genome Sequencing angewandt, mit Untersuchung von insgesamt 1423 Zielgenen und Klassifikation anhand ihres Komplextyps (CT). Die Ergebnisse dieser Studie zeigten, dass insbesondere gastroenterologische, nephro-logische und hämatoonkologische Normalstationen sowie Intensivstationen am UKR eine hohe VRE-Last aufwiesen, sich hinsichtlich der Häufigkeit anzunehmender Trans-missionsereignisse jedoch teilweise unterschieden. So waren insbesondere für die Intensivstationen vermehrt mögliche nosokomiale Nachweise zu registrieren. Zu bemer¬ken war hier zum einen ein fehlendes systematisches Screening und zum anderen ein hoher Patientenumsatz kritisch kranker Patienten. Die Gesamtgenomsequenzierung konnte zeigen, dass es sich bei den am UKR vorkom-menden Enterokokkenstämmen um ein polyklonales Geschehen handelte, mit vielen genetisch unterschiedlichen Enterokokkenstämmen. Einzelne Stämme waren im Rahmen der analysierten Ausbrüche und in Hochrisikobereichen jedoch dominierend als Hinweis auf ein erhöhtes Ausbreitungspotential dieser Stämme. Hier ist insbesondere der Enterokokkenstamm ST80 / CT1065 zu nennen. In Kombination mit detaillierten tagegenauen Patientenbewegungen ließen sich einige direkte Transmissionsereignisse nachweisen. Dies unter anderem dank sorgfältiger Erfassung von Risikopatienten und erfolgter Screeningmaßnahmen auf den Stationen. Gleichzeitig konnte jedoch beobachtet werden, dass viele – anhand epidemiologischer Daten, der van-Klassifikation und der MLST vermutete Transmis¬sionen – sich nicht bestätigen ließen. Passend hierzu war zu beobachten, dass häufig auch bei initial negativ gescreenten Patienten ein VRE-Nachweis erfolgte, ohne dass Indexpatienten eruiert werden konnten, die Transmissionswege also ungeklärt blieben. Zu diskutieren ist hier eine mögliche Selektion einer vorbestehenden VRE-Kolonisation unter Antibiotikatherapie ebenso wie eine Transmission des vanB-Transposons von Anaerobiern auf VSE mit konsekutiver klonaler Ausbreitung eines neuen Stam¬mes. Somit ist fraglich, ob allein die Detektion und Isolierung bekannter VRE-Träger ein sinn¬volles Management zur Kontrolle der Ausbreitung darstellt. Nicht VRE per se sondern einzelne Enterokokkenstämme wie der ST80 / CT1085 scheinen ein erhöhtes Ausbrei¬tungspotential zu haben. Daher sollten auch krankenhausadaptierte VSE in hygienere¬levante Überlegungen eingeschlossen werden. Somit könnte neben einer wirkungsvol¬len Reduktion von Transmissionen auch eine unnötige Kontaktisolation bei Nachweis von VRE mit geringem Ausbreitungspotential erzielt werden. Um bestimmte Risikokons¬tellationen zu erkennen und adäquat reagieren zu können, ist ein tief gehendes Verständnis über die Phylogenetik und Populationsstruktur der Enterokokken – sowohl VSE als auch VRE – notwendig. Dies ist nur durch konsequente Nachverfolgung und Gesamtgenomsequenzierung möglich. Ein neuartiges Konzept, das als Genom-orientierte Infektionsprävention bezeichnet wird. Bereits beste¬hende Datenbanken können genutzt werden, um sowohl national als auch international gewon¬nene Informationen auszutauschen und zusammenzuführen. Hiervon sollten nicht zuletzt die Patienten profitieren, um durch kontrollierende und präventive Maßnahmen Ausbrüche zu reduzieren und unnötige Isolationen, mit einhergehenden individuellen negativen medizinischen und psychosozialen Folgen, zu verhindern

Do Predictors Exist for a Successful Withdrawal of Preoperative Prostaglandin E1 from Neonates with d-Transposition of the Great Arteries and Intact Ventricular Septum?

Prostaglandin E1 (PGE1) is given to neonates with d-transposition of the great arteries (d-TGA) to reduce cyanosis by reopening and maintaining the patency of the ductus arteriosus. To avoid side effects, this medication can be stopped for hemodynamically stable patients after balloon atrial septostomy (BAS). A consecutive series of neonates with d-TGA and an intact ventricular septum (IVS) presenting from 2000 through 2005 was analyzed retrospectively to search for side effects of PGE1 and to identify predictors for a safe preoperative withdrawal. The medication was stopped for hemodynamically stable patients with transcutaneous oxygen saturations higher than 80% after BAS and reinitiated for patients with an oxygen saturation lower than 65%. Patients successfully weaned were compared with those who had failed weaning in terms of atrial septal defect (ASD) size, ductus arteriosus size, and the transcutaneous oxygen saturation. Prostaglandin E1 was initiated for all 43 neonates with d-TGA. The median maintenance dose of PGE1 was 0.00625μg/kg/min (range, 0.00313-0.050μg/kg/min) for a median duration of 6days (range, 1-12days). For 16 patients, PGE1 was preoperatively withdrawn but then had to be reinitiated for 7 of the 16 patients. No predictors for a successful weaning of PGE1 were found based on ASD size, ductus arteriosus size, or oxygen saturation. The adverse effects of PGE1 were apnea in 10 patients and fever in 19 patients. Neither seizures nor necrotizing enterocolitis was documented. Prostaglandin E1 was successfully withdrawn for a minority of hemodynamically stable patients with d-TGA. No predictors for a successful weaning could be identified. Because apnea and fever are common side effects, withdrawal of PGE1 after BAS may improve patient safety and comfort. In this patient group, if PGE1 withdrawal was not well tolerated, it could be safely reinitiated. There were no serious side effects of PGE

The effects of acute experimental hip muscle pain on dynamic single-limb balance performance in healthy middle-aged adults

Middle-aged adults with painful hip conditions show balance impairments that are consistent with an increased risk of falls. Pathological changes at the hip, accompanied by pain, may accelerate pre-existing age-related balance deficits present in midlife. To consider the influence of pain alone, we investigated the effects of acute experimental hip muscle pain on dynamic single-limb balance in middle-aged adults. Thirty-four healthy adults aged 40–60 years formed two groups (Group-1: n\ua0=\ua016; Group-2: n\ua0=\ua018). Participants performed four tasks: Reactive Sideways Stepping (ReactSide); Star Excursion Balance Test (SEBT); Step Test; Single-Limb Squat; before and after an injection of hypertonic saline into the right gluteus medius muscle (Group-1) or ∼5\ua0min rest (Group-2). Balance measures included the range and standard deviation of centre of pressure (CoP) movement in mediolateral and anterior-posterior directions, and CoP total path velocity (ReactSide, Squat); reach distance (SEBT); and number of completed steps (Step Test). Data were assessed using three-way analysis of variance. Motor outcomes were altered during the second repetition of tasks irrespective of exposure to experimental hip muscle pain or rest, with reduced SEBT anterior reach (−1.2\ua0±\ua04.1\ua0cm, P\ua0=\ua00.027); greater step number during Step Test (1.5\ua0±\ua01.7 steps, P\ua

Digital Platform Uses for Help and Support Seeking of Parents With Children Affected by Disabilities: Scoping Review

Background: Receiving a diagnosis that leads to severe disability in childhood can cause a traumatic experience with long-lasting emotional stress for patients and family members. In recent decades, emerging digital technologies have transformed how patients or caregivers of persons with disabilities manage their health conditions. As a result, information (eg, on treatment and resources) has become widely available to patients and their families. Parents and other caregivers can use digital platforms such as websites or social media to derive social support, usually from other patients and caregivers who share their lived experiences, challenges, and successes on these platforms. However, gaps remain in our understanding of platforms that are most frequently used or preferred among parents and caregivers of children with disabilities. In particular, it is not clear what factors primarily drive or discourage engagement with these digital tools and what the main ethical considerations are in relation to these tools. Objective: We aimed to (1) identify prominent digital platforms used by parents or caregivers of children with disabilities; (2) explore the theoretical contexts and reasons for digital platform use, as well as the experiences made with using these platforms reported in the included studies; and (3) identify any privacy and ethical concerns emerging in the available literature in relation to the use of these platforms. Methods: We conducted a scoping review of 5 academic databases of English-language articles published within the last 10 years for diseases with childhood onset disability and self-help or parent/caregiver-led digital platforms. Results: We identified 17 papers in which digital platforms used by parents of affected children predominantly included social media elements but also search engines, health-related apps, and medical websites. Information retrieval and social support were the main reasons for their utilization. Nearly all studies were exploratory and applied either quantitative, qualitative, or mixed methods. The main ethical concerns for digital platform users included hampered access due to language barriers, privacy issues, and perceived suboptimal advice (eg, due to missing empathy of medical professionals). Older and non–college-educated individuals and ethnic minorities appeared less likely to access information online. Conclusions: This review showed that limited scientifically sound knowledge exists on digital platform use and needs in the context of disabling conditions in children, as the evidence consists mostly of exploratory studies. We could highlight that affected families seek information and support from digital platforms, as health care systems seem to be insufficient for satisfying knowledge and support needs through traditional channels

In-situ and label-free optical monitoring of the adhesion and spreading of primary monocytes isolated from human blood: dependence on serum concentration levels

Adhesion and spreading of primary monocytes isolated from human blood were monitored utilizing optical waveguide lightmode spectroscopy (OWLS); a highly sensitive label-free biosensor technique using evanescent optical waves generated at a biocompatible surface. Appropriate development on a custom built setup enabled the OWLS cuvette to be operated as a 1.5 ml mini-incubator, controlling both temperature and CO2 levels. The incubator-equipped OWLS is readily applicable for delicate and long-term studies on sensitive primary cells, demonstrated here through monitoring the serum dependence of the adhesion and spreading of human monocytes. Moreover, the custom-built setup enables the simultaneous monitoring of the position and overall width of the OWLS resonant peaks. This unique feature makes it possible to distinguish the refractive index variations induced by the adsorption of secreted material from refractive index changes provoked by cellular spreading. A definite attachment and spreading activity was observed on the substratum (glassy silica-titania), when the serum level of the culturing medium was 0.0-0.01%. Increasing serum concentration resulted in a steep fall in monocyte surface adhesion and spreading. 1.0% serum level practically abolished all spreading activity measured by OWLS, and the number of attached cells was significantly decreased, too. Serum addition to fully spread cells provoked a reduction in the cell-substratum contact area, clearly detectable by the biosensor. Cell spreading was inhibited by pre-coating the sensor surface with considerable amounts of serum proteins. These findings suggest that monocyte spreading is inhibited by the adsorption of serum biomolecules to the substratum, rather than by soluble factors present in the serum. All of these results were obtained completely non-invasively with real time monitoring; demonstrating the capabilities of OWLS to sensitively monitor the adhesion properties of immune cells isolated from human blood. The current study is, therefore, a significant step towards the application of label-free optical biosensors in medical diagnostics

Mental health challenges and digital platform opportunities in patients and families affected by pediatric neuromuscular diseases - experiences from Switzerland

Receiving the diagnosis of a severe disease may present a traumatic event for patients and their families. To cope with the related challenges, digital interventions can be combined with traditional psychological support to help meet respective needs. We aimed to 1) discuss the most common consequences and challenges for resilience in Neuro Muscular Disease patients and family members and 2) elicit practical needs, concerns, and opportunities for digital platform use. We draw from findings of a transdisciplinary workshop and conference with participants ranging from the fields of clinical practice to patient representatives. Reported consequences of the severe diseases were related to psychosocial challenges, living in the nexus between physical development and disease progression, social exclusion, care-related challenges, structural and financial challenges, and non-inclusive urban design. Practical needs and concerns regarding digital platform use included social and professional support through these platforms, credibility and trust in online information, and concerns about privacy and informed consent. Furthermore, the need for safe, reliable, and expert-guided information on digital platforms and psychosocial and relationship-based digital interventions was expressed. There is a need to focus on a family-centered approach in digital health and social care and a further need in researching the suitability of digital platforms to promote resilience in the affected population. Our results can also inform city councils regarding investments in inclusive urban design allowing for disability affected groups to enjoy a better quality of life

Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study

<p/> <p>Background</p> <p>Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours.</p> <p>Methods/Design</p> <p>The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial.</p> <p>Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points.</p> <p>Discussion</p> <p>Up to now it was impossible to compare two different particle therapies, i.e. protons and carbon ions, directly at the same facility in connection with the treatment of low grade skull base chondrosarcomas.</p> <p>This trial is a phase III study to demonstrate that carbon ion radiotherapy (experimental treatment) is not relevantly inferior and at least as good as proton radiotherapy (standard treatment) with respect to 5 year LPFS in the treatment of chondrosarcomas. Additionally, we expect less toxicity in the carbon ion treatment arm.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT01182753</p

Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events