Surfactantproteine und ihre Vorstufen bei interstitiellen Lungenerkrankungen im Kindesalter

Veränderungen des intrazellulären Metabolismus der Surfactantproteine SP-C und SP-B sowie ihrer Vorstufen, sind in manchen Fällen verantwortlich für chronische interstitielle Lungenerkrankungen sowie unklare respiratorische Insuffizienz im Kindesalter. Um Häufigkeit und mögliche diagnostische Bedeutung dieser Veränderung zu untersuchen, analysierten wir die bronchoalveolären Lavagen von Kindern mit unklaren ILE (ILD n=49), unklarer respiratorischer Insuffizienz bei Neugeborenen (NG n=36) und unklarer respiratorischer Insuffizienz bei nicht Neugeborenen (n=7), im Vergleich zu Kindern ohne Lungenerkrankungen (n=12). Matures SP-B fand sich in allen untersuchten Fällen und schloss so eine SP- Defizienz biochemisch bei diesen Kindern aus. Die Vorformen von SP-B, pro-SP-B fanden sich bei der überwiegenden Mehrzahl der Kinder, neue oder unerwartete Banden ließen sich nicht nachweisen. Eine biochemisches Fehlen von SP-C fanden wir bei elf Proben; von diesen wurde eine genetisch auf Mutationen im SP-C Gen untersucht, eine genetische SP-C-Defizienz ließ sich nicht nachweisen. Zwei der elf Proben wurden für Mutationen im ABCA-3-Transporter untersucht, diese ließen sich bei beiden nachweisen. Des Weiteren zeigten sich bei vier Kindern Mutationen im ABCA-3-Transporter ohne das SP-C biochemisch untersucht worden war, sodass wir insgesamt bei sechs Kindern Mutationen im codierenden Bereich für den ABCA-3-Transporter nachweisen konnten. Fehlendes oder erniedrigtes SP-C in der Lavage weißt bei entsprechender Klinik auf Defekte im SP-C oder ABCA-3-Gen hin. Normalerweise findet sich kein pro-SP-C in der Lavage; wir konnten allerdings Signale nachweisen. Bei einem der drei Patienten mit genetisch determinierter SP-C-Defizienz zeigte die Probe Signale. Die quantitative Auswertung der Surfactantproteinmengen ergab keine Unterschiede zwischen den Gruppen. Leider wurde (und konnte aufgrund fehlender DNA oder Einverständniserklärungen) nur bei einem kleinen Teil der Kinder eine genetische Untersuchung durchgeführt. Ebenso zeigte unsere Auswertung der durchgeführten Diagnostik, dass viel zu selten weiterführende diagnostische Maßnahmen wie HR-CT oder Biopsien vorgenommen wurden. Bei persistierender Symptomatik sollte auch in dieser Altersgruppe entgegen der aktuellen klinischen Alltagsvorgehensweise, nach Ausschluss exogener Ursachen sowie von Systemerkrankungen, eine definitive Diagnosestellung vorangetrieben werden. Nur so kann eine ätiologische Einordnung erfolgen und es können rationale Therapieeinsätze geplant werden

Screening and treatment for tuberculosis in a cohort of unaccompanied minor refugees in Berlin, Germany

INTRODUCTION: In 2015, 4062 unaccompanied minor refugees were registered in Berlin, Germany. According to national policies, basic clinical examination and tuberculosis (TB) screening is a prerequisite to admission to permanent accommodation and schooling for every refugee. This article evaluates the use of an interferon-γ-release-assay (IGRA) during the initial examination and TB screening of 970 unaccompanied minor refugees. RESULTS: IGRA test were obtained during TB screening for 301 (31.0%) of 970 adolescents not previously screened for TB. Positive IGRA results were obtained in 13.9% (42/301). Most of the 42 IGRA-positive refugees originated from Afghanistan or Syria (n?20 and 10 respectively). Two IGRA-positive adolescents were lost to follow-up, 2 were diagnosed with TB and the remaining 38 diagnosed with latent TB infection (LTBI). Demographic features of the 40 patients with positive IGRA result were as follows: 39 male, median age 16.8 years (IQR 16.0-17.2y), none meeting underweight criteria (median BMI 21.3kg/m2). On initial chest X-ray 2/40 participants had signs of active TB, while in 38 active disease was excluded and the diagnosis of latent TB infection (LTBI) made. Active hepatitis B-co-infection was diagnosed in 3/38 patients. All patients with LTBI received Isoniazid and Rifampicin for 3 months without occurrence of severe adverse events. The most frequently observed side effect was transient upper abdominal pain (n = 5). Asymptomatic elevation of liver transaminases was seen in 2 patients. 29 patients completed treatment with no signs of TB disease at the end of chemoprevention and 9 were lost to follow up. CONCLUSION: Screening for TB infection in minor refugees was feasible in our setting with a relatively high rate of TB infection detected. Chemopreventive treatment was tolerated well regardless of underlying hepatitis-B-status. Minor refugees migrating to Germany should be screened for TB infection, instead of TB disease only, regardless of the background TB incidence

Web-based patient-reported outcomes using the International Consortium for Health Outcome Measurement dataset in a major German university hospital: observational study

Background: Collecting patient-reported outcome (PRO) data systematically enables objective evaluation of treatment and its related outcomes. Using disease-specific questionnaires developed by the International Consortium for Health Outcome Measurement (ICHOM) allows for comparison between physicians, hospitals, and even different countries. Objective: This pilot project aimed to establish a digital system to measure PROs for new patients with breast cancer who attended the Charité Breast Center. This approach should serve as a blueprint to further expand the PRO measurement to other disease entities and departments. Methods: In November 2016, we implemented a Web-based system to collect PRO data at Charité Breast Center using the ICHOM dataset. All new patients at the Breast Center were enrolled and answered a predefined set of questions using a tablet computer. Once they started their treatment at Charité, automated emails were sent to the patients at predefined treatment points. Those emails contained a Web-based link through which they could access and answer questionnaires. Results: By now, 541 patients have been enrolled and 2470 questionnaires initiated. Overall, 9.4% (51/541) of the patients were under the age of 40 years, 49.7% (269/541) between 40 and 60 years, 39.6% (214/541) between 60 and 80 years, and 1.3% (7/541) over the age of 80 years. The average return rate of questionnaires was 67.0%. When asked about the preference regarding paper versus Web-based questionnaires, 6.0% (8/134) of the patients between 50 and 60 years, 6.0% (9/150) between 60 and 70 years, and 12.7% (9/71) over the age of 70 years preferred paper versions. Conclusions: Measuring PRO in patients with breast cancer in an automated electronic version is possible across all age ranges while simultaneously achieving a high return rate

2ʹ-Deoxyadenosine 5ʹ-diphosphoribose is an endogenous TRPM2 superagonist

Transient receptor potential melastatin 2 (TRPM2) is a ligand-gated Ca2+-permeable nonselective cation channel. Whereas physiological stimuli, such as chemotactic agents, evoke controlled Ca2+ signals via TRPM2, pathophysiological stimuli such as reactive oxygen species and genotoxic stress result in prolonged TRPM2-mediated Ca2+ entry and, consequently, apoptosis. To date, adenosine 5'-diphosphoribose (ADPR) has been assumed to be the main agonist for TRPM2. Here we show that 2'-deoxy-ADPR was a significantly better TRPM2 agonist, inducing 10.4-fold higher whole-cell currents at saturation. Mechanistically, this increased activity was caused by a decreased rate of inactivation and higher average open probability. Using high-performance liquid chromatography (HPLC) and mass spectrometry, we detected endogenous 2'-deoxy-ADPR in Jurkat T lymphocytes. Consistently, cytosolic nicotinamide mononucleotide adenylyltransferase 2 (NMNAT-2) and nicotinamide adenine dinucleotide (NAD)-glycohydrolase CD38 sequentially catalyzed the synthesis of 2'-deoxy-ADPR from nicotinamide mononucleotide (NMN) and 2'-deoxy-ATP in vitro. Thus, 2'-deoxy-ADPR is an endogenous TRPM2 superagonist that may act as a cell signaling molecule

Staff and parents are discriminators for outcomes in neonatal intensive care units

AimWe investigated the associations between staff work characteristics, parents' experiences and a number of medical outcome measures. MethodsThis explorative multicentre study took place in the neonatal intensive care units (NICUs) of five German university hospitals between 2009 and 2011. We assessed staff work characteristics by surveying 126 NICU nurses and 57 physicians and asked 214 parents about their relationships with staff. The outcome variables of 230 premature infants with birth weights of less than 1500g were collected over a period of 18months. We used analysis of variance (ANOVA) and regression analyses for statistical purposes. ResultsWe found differences in outcome measures between the NICUs, particularly parameters of respiratory support, weight gain and length of stay. When we controlled for the NICUs' baseline factors, perceptions of the relationship between staff and parents (empathy, p<0.001; conversation duration and frequency, p<0.05; familiarity, p<0.05) and staff work characteristics (workload, p<0.05) were associated with at least one of these outcome measures. ConclusionStaff and parents were discriminators for neonatal outcomes through perceptions of work characteristics and the relationship between staff and parents, respectively. Respiratory support and nutrition measures were particularly sensitive. This research has prompted a nationwide, multicentre study of 66 NICUs

Interdisciplinary Online Hackathons as an Approach to Combat the COVID-19 Pandemic: Case Study

Background: The COVID-19 outbreak has affected the lives of millions of people by causing a dramatic impact on many health care systems and the global economy. This devastating pandemic has brought together communities across the globe to work on this issue in an unprecedented manner. Objective: This case study describes the steps and methods employed in the conduction of a remote online health hackathon centered on challenges posed by the COVID-19 pandemic. It aims to deliver a clear implementation road map for other organizations to follow. Methods: This 4-day hackathon was conducted in April 2020, based on six COVID-19-related challenges defined by frontline clinicians and researchers from various disciplines. An online survey was structured to assess: (1) individual experience satisfaction, (2) level of interprofessional skills exchange, (3) maturity of the projects realized, and (4) overall quality of the event. At the end of the event, participants were invited to take part in an online survey with 17 (+5 optional) items, including multiple-choice and open-ended questions that assessed their experience regarding the remote nature of the event and their individual project, interprofessional skills exchange, and their confidence in working on a digital health project before and after the hackathon. Mentors, who guided the participants through the event, also provided feedback to the organizers through an online survey. Results: A total of 48 participants and 52 mentors based in 8 different countries participated and developed 14 projects. A total of 75 mentorship video sessions were held. Participants reported increased confidence in starting a digital health venture or a research project after successfully participating in the hackathon, and stated that they were likely to continue working on their projects. Of the participants who provided feedback, 60% (n=18) would not have started their project without this particular hackathon and indicated that the hackathon encouraged and enabled them to progress faster, for example, by building interdisciplinary teams, gaining new insights and feedback provided by their mentors, and creating a functional prototype. Conclusions: This study provides insights into how online hackathons can contribute to solving the challenges and effects of a pandemic in several regions of the world. The online format fosters team diversity, increases cross-regional collaboration, and can be executed much faster and at lower costs compared to in-person events. Results on preparation, organization, and evaluation of this online hackathon are useful for other institutions and initiatives that are willing to introduce similar event formats in the fight against COVID-19

Integration of mobile sensors in a telemedicine hospital system: remote-monitoring in COVID-19 patients

Aim!#!The goal is to design and, in a next step, establish a scalable, multi-center telemonitoring platform based on existing systems for monitoring COVID-19 patients in home quarantine. In particular, the focus will be on raw data acquisition, integration of sensor data into the hospital system, structured data storage, and interoperability.!##!Subject and methods!#!Data necessary for monitoring, otherwise provided in various portals, will be continuously queried and integrated into the hospital system via a new interface in this proof-of-concept work.!##!Results!#!Based on extensive preliminary work at Klinikum rechts der Isar with a structured clinical database, we extend our system's integration of raw data and visualization in dashboards, as well as scientific provision of data from mobile sensors for monitoring patients in home quarantine.!##!Conclusion!#!Based on existing integrated telemonitoring systems supporting semantic and syntactic interoperability, short-term provision of scientific databases is possible. The integration of different mobile sensors into a clinical system for remote monitoring of patients around the clock is still new and to our knowledge unique

Clinical evaluation of a web-based personalized recommendation system with electronic health record interface to optimize healthcare resources during SARS-CoV-2 surges

Abstract During the SARS-CoV-2 pandemic, the German healthcare system faced challenges of efficiently allocating testing resources. To address this, we developed an open-source personalized recommendation system (PRS) called “CovApp”. The PRS utilized a questionnaire to estimate the risk of infection, provided personalized recommendations such as testing, self-isolation, or quarantine, and featured QR code data transmission to electronic health records. The PRS served up to 2.5 million monthly users and received 67,000 backlinks from 1800 domains. We clinically evaluated the PRS at the SARS-CoV-2 testing facility at Charité and observed a 21.7% increase in patient throughput per hour and a 22.5% increase in patients per day. Patients using the PRS were twice as likely to belong to the High Risk group eligible for testing (18.6% vs. 8.9%, p < 0.0001), indicating successful compliance with CovApp’s recommendations. CovApp served as a digital bridge between the population and medical staff and significantly improved testing efficiency. As an open-source platform, CovApp can be readily customized to address emerging public health crises. Further, given the EHR interface, the app is of great utility for other applications in clinical settings

The Roadmap for Implementing Value-Based Healthcare in European University Hospitals—Consensus Report and Recommendations

Objectives: Value-based healthcare (VBHC) aims at improving patient outcomes while optimizing the use of hospitals’ resources among medical personnel, administrations, and support services through an evidence-based, collaborative approach. In this article, we present a blueprint for the implementation of VBHC in hospitals, based on our experience as members of the European University Hospital Alliance. Methods: The European University Hospital Alliance is a consortium of 9 large hospitals in Europe and aims at increasing the quality and efficiency of care to ultimately drive better outcomes for patients. Results: The blueprint describes how to prepare hospitals for VBHC implementation; analyzes gaps, barriers, and facilitators; and explores the most effective ways to turn patient pathways into a process that results in high-value care. Using a patient-centric approach, we identified 4 core minimum components that must be established as cornerstones and 7 organizational enablers to waive the barriers to implementation and ensure sustainability. Conclusion: The blueprint guides through pathway implementation and establishment of key performance indicators in 6 phases, which hospitals can tailor to their current status on their way to implement VBHC

SARS-CoV-2 infection and transmission in school settings during the second wave in Berlin, Germany: a cross-sectional study

Background: School attendance during the SARS-CoV-2 pandemic is intensely debated. Modelling studies suggest that school closures contribute to community transmission reduction. However, data among school-attending students and staff are scarce. In November 2020, we examined SARS-CoV-2 infections and seroreactivity in 24 randomly selected school classes and connected households in Berlin, Germany. Methods: Students and school staff were examined, oro-nasopharyngeal swabs and blood samples collected, and SARS-CoV-2 infection and IgG antibodies detected by RT-PCR and ELISA. Household members performed self-swabs. Individual and institutional infection prevention and control measures were assessed. Classes with SARS-CoV-2 infection and connected household members were re-tested after one week. Findings: 1119 participants were examined, including 177 primary and 175 secondary school students, 142 staff, and 625 household members. Participants reported mainly cold symptoms (19·4%). SARS-CoV-2 infection occurred in eight of 24 classes affecting each 1-2 individuals. Infection prevalence was 2·7% (95%CI; 1·2-5·0%; 9/338), 1·4% (0·2-5·1%; 2/140), and 2·3% (1·3-3·8%; 14/611) among students, staff and household members, respectively, including quarantined persons. Six of nine infected students were asymptomatic. Prevalence increased with inconsistent facemask use in school, way to school on foot, and case-contacts outside school. IgG antibodies were detected in 2·0% (0·8-4·1%; 7/347), 1·4% (0·2-5·0%; 2/141) and 1·4% (0·6-2·7%; 8/576), respectively. For three of nine households with infection(s) detected at cross-sectional assessment, origin in school seemed possible. After one week, no school-related, secondary infections appeared in affected classes; the attack rate in connected households was 1·1%. Interpretation: These data suggest that school attendance under preventive measures is feasible, provided their rigorous implementation. In balancing threats and benefits of open versus closed schools during the pandemic, parents and society need to consider possible spill-overs into their households. Deeper insight is needed into the infection risks due to being a schoolchild as compared to attending school