A symptom-related monitoring program following pulmonary embolism for the early detection of CTEPH: a prospective observational registry study

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term complication following an acute pulmonary embolism (PE). It is frequently diagnosed at advanced stages which is concerning as delayed treatment has important implications for favourable clinical outcome. Performing a follow-up examination of patients diagnosed with acute PE regardless of persisting symptoms and using all available technical procedures would be both cost-intensive and possibly ineffective. Focusing diagnostic procedures therefore on only symptomatic patients may be a practical approach for detecting relevant CTEPH. This study aimed to evaluate if a follow-up program for patients with acute PE based on telephone monitoring of symptoms and further examination of only symptomatic patients could detect CTEPH. In addition, we investigated the role of cardiopulmonary exercise testing (CPET) as a diagnostic tool. Methods In a prospective cohort study all consecutive patients with newly diagnosed PE (n=170, 76 males, 94 females within 26 months) were recruited according to the inclusion and exclusion criteria. Patients were contacted via telephone and asked to answer standardized questions relating to symptoms. At the time of the final analysis 130 patients had been contacted. Symptomatic patients underwent a structured evaluation with echocardiography, CPET and complete work-up for CTEPH. Results 37.7%, 25.5% and 29.3% of the patients reported symptoms after three, six, and twelve months respectively. Subsequent clinical evaluation of these symptomatic patients saw 20.4%, 11.5% and 18.8% of patients at the respective three, six and twelve months time points having an echocardiography suggesting pulmonary hypertension (PH). CTEPH with pathological imaging and a mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg at rest was confirmed in eight subjects. Three subjects with mismatch perfusion defects showed an exercise induced increase of PAP without increasing pulmonary artery occlusion pressure (PAOP). Two subjects with pulmonary hypertension at rest and one with an exercise induced increase of mPAP with normal PAOP showed perfusion defects without echocardiographic signs of PH but a suspicious CPET. Conclusion A follow-up program based on telephone monitoring of symptoms and further structured evaluation of symptomatic subjects can detect patients with CTEPH. CPET may serve as a complementary diagnostic tool

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process

Background Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage. Methods This cross-sectional study was conducted at 30 pediatric hematology and oncology centers in 2020 and 2021. Centers affiliated to the German Society for Pediatric Oncology and Hematology were invited to join, and an existing institutional standard was a prerequisite to participate. We included hematologic/oncologic inpatients under 19 years old, who had a systemic antimicrobial treatment on the day of the point prevalence survey. In addition to a one-day, point-prevalence survey, external experts individually assessed the appropriateness of each therapy. This step was followed by an expert panel adjudication based upon the participating centers’ institutional standards, as well as upon national guidelines. We analyzed antimicrobial prevalence rate, along with the rate of appropriate, inappropriate, and indeterminate antimicrobial therapies with regard to institutional and national guidelines. We compared the results of academic and non-academic centers, and performed a multinomial logistic regression using center- and patient-related data to identify variables that predict inappropriate therapy. Findings At the time of the study, a total of 342 patients were hospitalized at 30 hospitals, of whom 320 were included for the calculation of the antimicrobial prevalence rate. The overall antimicrobial prevalence rate was 44.4% (142/320; range 11.1–78.6%) with a median antimicrobial prevalence rate per center of 44.5% (95% confidence interval [CI] 35.9–49.9). Antimicrobial prevalence rate was significantly higher (p < 0.001) at academic centers (median 50.0%; 95% CI 41.2–55.2) compared to non-academic centers (median 20.0%; 95% CI 11.0–32.4). After expert panel adjudication, 33.8% (48/142) of all therapies were labelled inappropriate based upon institutional standards, with a higher rate (47.9% [68/142]) when national guidelines were taken into consideration. The most frequent reasons for inappropriate therapy were incorrect dosage (26.2% [37/141]) and (de-)escalation/spectrum-related errors (20.6% [29/141]). Multinomial, logistic regression yielded the number of antimicrobial drugs (odds ratio, OR, 3.13, 95% CI 1.76–5.54, p < 0.001), the diagnosis febrile neutropenia (OR 0.18, 95% CI 0.06–0.51, p = 0.0015), and an existing pediatric antimicrobial stewardship program (OR 0.35, 95% CI 0.15–0.84, p = 0.019) as predictors of inappropriate therapy. Our analysis revealed no evidence of a difference between academic and non-academic centers regarding appropriate usage. Interpretation Our study revealed there to be high levels of antimicrobial usage at German and Austrian pediatric oncology and hematology centers with a significant higher number at academic centers. Incorrect dosing was shown to be the most frequent reason for inappropriate usage. Diagnosis of febrile neutropenia and antimicrobial stewardship programs were associated with a lower likelihood of inappropriate therapy. These findings suggest the importance of febrile neutropenia guidelines and guidelines compliance, as well as the need for regular antibiotic stewardship counselling at pediatric oncology and hematology centers. Funding European Society of Clinical Microbiology and Infectious Diseases, Deutsche Gesellschaft für Pädiatrische Infektiologie, Deutsche Gesellschaft für Krankenhaushygiene, Stiftung Kreissparkasse Saarbrücken

MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation.

Stephan T, Bruser C, Deckers M, et al. MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation. The EMBO journal. 2020: e104105.Mitochondrial function is critically dependent on the folding of the mitochondrial inner membrane into cristae; indeed, numerous human diseases are associated with aberrant crista morphologies. With the MICOS complex, OPA1 and the F1 Fo -ATP synthase, key players of cristae biogenesis have been identified, yet their interplay is poorly understood. Harnessing super-resolution light and 3D electron microscopy, we dissect the roles of these proteins in the formation of cristae in human mitochondria. We individually disrupted the genes of all seven MICOS subunits in human cells and re-expressed Mic10 or Mic60 in the respective knockout cell line. We demonstrate that assembly of the MICOS complex triggers remodeling of pre-existing unstructured cristae and de novo formation of crista junctions (CJs) on existing cristae. We show that the Mic60-subcomplex is sufficient for CJ formation, whereas the Mic10-subcomplex controls lamellar cristae biogenesis. OPA1 stabilizes tubular CJs and, along with the F1 Fo -ATP synthase, fine-tunes the positioning of the MICOS complex and CJs. We propose a new model of cristae formation, involving the coordinated remodeling of an unstructured crista precursor into multiple lamellar cristae. © 2020 The Authors. Published under the terms of the CC BY 4.0 license

On Teaching International Courses on Health Information Systems: Lessons Learned during 16 Years of Frank – van Swieten Lectures on Strategic Information Management in Health Information Systems

Background: Health information systems (HIS) are one of the most important areas for biomedical and health informatics. In order to professionally deal with HIS well-educated informaticians are needed. Because of these reasons, in 2001 an international course has been established: The Frank – van Swieten Lectures on Strategic Information Management of Health Information Systems. Objectives: Reporting about the Frank – van Swieten Lectures and about our students‘ feedback on this course during the last 16 years. Summarizing our lessons learned and making recommendations for such international courses on HIS. Methods: The basic concept of the Frank – van Swieten lectures is to teach the theoretical background in local lectures, to organize practical exercises on modelling sub-information systems of the respective local HIS and finally to conduct Joint Three Days as an international meeting were the resulting models are introduced and compared. Results: During the last 16 years, the Universities of Amsterdam, Braunschweig, Heidelberg/Heilbronn, Leipzig as well as UMIT were involved in running this course. Overall, 517 students from these universities participated. Our students‘ feedback was clearly positive. The Joint Three Days of the Frank – van Swieten Lectures, where at the end of the course all students can meet, turned out to be an important component of this course. Based on the last 16 years, we recommend common teaching materials, agreement on equivalent clinical areas for the exercises, support of group building of international student groups, motivation of using a collaboration platform, ensuring quality management of the course, addressing different levels of knowledge of the students, and ensuring sufficient funding for joint activities. Conclusions: Although associated with considerable additional efforts, we can clearly recommend establishing such international courses on HIS, such as the Frank – van Swieten Lectures