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Zusammenfassung Hintergrund Im Medizinstudium in Deutschland ist seit 2016 ein gesonderter Leistungsnachweis auf dem Gebiet der Schmerzmedizin zu erwerben. Bislang fehlen Untersuchungen über die Effekte dieser Einführung auf Kompetenzen von Studierenden im Themengebiet Schmerzmedizin. Ziel der Arbeit Ziel war es herauszufinden, inwieweit die Einführung des Fachgebiets Schmerzmedizin als Querschnittsbereich 14 den Kompetenzerwerb der Studierenden im Bereich Schmerzmedizin gemessen über eine Selbsteinschätzung positiv beeinflusst. Material und Methoden Die Entwicklung des longitudinalen Curriculums wurde mithilfe des Kern-Zyklus durchgeführt. Parallel erfolgte die Erstellung eines Fragebogens zur Selbsteinschätzung der Studierenden auf einer 5‑stufigen Likert-Skala bzgl. des eigenen Wissensstands und der Bedeutung schmerzmedizinischer Lehrinhalte. Die Befragungen wurden vor Einführung der Veranstaltungsreihe (2014), nach Abschluss der ersten Kohorte (2016) und 5 Jahre nach Einführung (2019) durchgeführt und mittels Kruskal-Wallis-Tests verglichen. Ergebnisse Die Einführung des Curriculums hat zu einer signifikanten Verbesserung in relevanten Punkten geführt. So fühlen sich die Studierenden insgesamt besser auf die Behandlung von Schmerzpatienten vorbereitet (2,67 im Jahr 2014 vs. 3,18 im Jahr 2019). Teilaspekte wie die Erhebung einer Schmerzanamnese (3,63 vs. 4,10) oder die Erstellung eines Analgesieschemas (3,56 vs. 4,14) werden nun subjektiv deutlich besser beherrscht. Diskussion Trotz erfreulicher Ergebnisse besteht in Teilbereichen noch Verbesserungspotenzial. Beispielsweise ist die Bewertung der Studierenden zur Frage nach der Vorbereitung auf die Behandlung von Schmerzpatienten noch nicht zufriedenstellend. Hier gilt es, das Curriculum mit Fokus auf die Kompetenzorientierung weiterzuentwickeln. Dabei können digitale Lehrformate ebenso integriert werden wie interprofessionelle Einheiten und Simulationspatienten. Zudem sind jedoch gleichzeitig auch die Prüfungsformate hin zu standardisierten praktischen Prüfungen weiterzuentwickeln.

Background: Recent data suggest that anesthesiologic interventions—e.g., the choice of the anesthetic regimen or the administration of blood products—might play a major role in determining outcome after tumor surgery. In contrast to adult patients, only limited data are available regarding the potential association of anesthesia and outcome in pediatric cancer patients. Methods: A retrospective multicenter study assessing data from pediatric patients (0–18 years of age) undergoing surgery for nephroblastoma between 2004 and 2018 was conducted at three academic centers in Europe. Overall and recurrence-free survival were the primary outcomes of the study and were evaluated for a potential impact of intraoperative administration of erythrocyte concentrates, the use of regional anesthesia and the choice of the anesthetic regimen. The length of stay on the intensive care unit, the time to hospital discharge after surgery and blood neutrophil-to-lymphocyte ratio were defined as secondary outcomes. Results: In total, data from 65 patients were analyzed. Intraoperative administration of erythrocyte concentrates was associated with a reduction in recurrence-free survival (hazard ratio (HR) 7.59, 95% confidence interval (CI) 1.36–42.2, p = 0.004), whereas overall survival (HR 5.37, 95% CI 0.42–68.4, p = 0.124) was not affected. The use of regional anesthesia and the choice of anesthetic used for maintenance of anesthesia did not demonstrate an effect on the primary outcomes. It was, however, associated with fewer ICU transfers, a shortened time to discharge and a decreased postoperative neutrophil-to-lymphocyte ratio. Conclusions: The current study provides the first evidence for a possible association between blood transfusion as well as anesthesiologic interventions and outcome after pediatric cancer surgery.

As a part of a major reform of the medical curriculum in Germany, the national catalogue of learning objectives is being revised with the focus shifting from theory-based learning to teaching practical skills. Therefore, we conducted an online survey to answer the question, which practical skills are essential in anesthesia. Participants were asked to rate the relevance of several skills, that medical students should be able to perform at the time of graduation. A total of 2898 questionnaires could be evaluated. The highest ratings were made for “bringing a patient into lateral recumbent position” and “diagnosing a cardiac arrest”. All learning objectives regarding regional anesthesia were rated as irrelevant. Furthermore, learning objectives like “performing a bronchoscopy” or “performing a rapid sequence induction” had low ratings. In the subgroup analysis, physicians with advanced training and those who were working at university hospitals rated most skills with higher relevance compared to others. Our survey provides a good prioritization of practical skills for the development of new curricula and assessment frameworks. The results can also help to establish our discipline as a cross-sectional subject in competency-based medical education, thus further increasing the attractiveness for medical students.

Endoreplication, duplication of the nuclear genome without cell division, occurs in disease to drive morphologic growth, cell fate, and function. Despite its criticality, the metabolic underpinnings of disease-induced endoreplication and its link to morphologic growth are unknown. Heart disease is characterized by endoreplication preceding cardiac hypertrophy. We identify ATP synthase as a central control node and determinant of cardiac endoreplication and hypertrophy by rechanneling free mitochondrial ADP to methylenetetrahydrofolate dehydrogenase 1 L (MTHFD1L), a mitochondrial localized rate-limiting enzyme of formate and de novo nucleotide biosynthesis. Concomitant activation of the adenosine monophosphate–activated protein kinase (AMPK)–retinoblastoma protein (Rb)-E2F axis co-opts metabolic products of MTHFD1L function to support DNA endoreplication and pathologic growth. Gain- and loss-of-function studies in genetic and surgical mouse heart disease models and correlation in individuals confirm direct coupling of deregulated energetics with endoreplication and pathologic overgrowth. Together, we identify cardiometabolic endoreplication as a hitherto unknown mechanism dictating pathologic growth progression in the failing myocardium.

The field of pain medicine was established as an obligatory subject area of medical schools in Germany in 2016. No prior study has evaluated the effects of this curricular change on students' competences in the field of pain medicine.The aim of this study was to find out to what extent the introduction of the additional subject "pain medicine" positively influenced the students' acquisition of competences measured via a self-assessment.A longitudinal and interdisciplinary curriculum for pain medicine was developed according to the current recommendations for curriculum development for medical education. In parallel, a questionnaire was created for the students' self-assessment of their own level of knowledge and the importance of pain medicine teaching content on a 5-stage Likert scale. The surveys were conducted before the implementation of the curriculum (2014), directly after the first cohort finished (2016) and 5 years after the implementation (2019) and compared by Kruskal-Wallis test.The implementation of the curriculum has led to significant improvement in relevant aspects. For example, students now feel better prepared overall for the treatment of pain patients (2.67 in 2014 vs. 3.18 in 2019). Individual sub-aspects such as taking a pain history (3.63 vs. 4.10) or drawing up an analgesia scheme (3.56 vs. 4.14) are now also subjectively better mastered.Even though the results are encouraging, there is further potential for improvement in some sub-areas. For example, the students' rating regarding the question about their preparation for treating patients in pain is not yet satisfactory. Therefore, the curriculum should be developed further with a focus on competence orientation. Digital teaching formats can be integrated as well as interprofessional units and simulated patients. Additionally, the examination formats should be further developed towards standardized practical examinations.HINTERGRUND: Im Medizinstudium in Deutschland ist seit 2016 ein gesonderter Leistungsnachweis auf dem Gebiet der Schmerzmedizin zu erwerben. Bislang fehlen Untersuchungen über die Effekte dieser Einführung auf Kompetenzen von Studierenden im Themengebiet Schmerzmedizin.Ziel war es herauszufinden, inwieweit die Einführung des Fachgebiets Schmerzmedizin als Querschnittsbereich 14 den Kompetenzerwerb der Studierenden im Bereich Schmerzmedizin gemessen über eine Selbsteinschätzung positiv beeinflusst.Die Entwicklung des longitudinalen Curriculums wurde mithilfe des Kern-Zyklus durchgeführt. Parallel erfolgte die Erstellung eines Fragebogens zur Selbsteinschätzung der Studierenden auf einer 5‑stufigen Likert-Skala bzgl. des eigenen Wissensstands und der Bedeutung schmerzmedizinischer Lehrinhalte. Die Befragungen wurden vor Einführung der Veranstaltungsreihe (2014), nach Abschluss der ersten Kohorte (2016) und 5 Jahre nach Einführung (2019) durchgeführt und mittels Kruskal-Wallis-Tests verglichen.Die Einführung des Curriculums hat zu einer signifikanten Verbesserung in relevanten Punkten geführt. So fühlen sich die Studierenden insgesamt besser auf die Behandlung von Schmerzpatienten vorbereitet (2,67 im Jahr 2014 vs. 3,18 im Jahr 2019). Teilaspekte wie die Erhebung einer Schmerzanamnese (3,63 vs. 4,10) oder die Erstellung eines Analgesieschemas (3,56 vs. 4,14) werden nun subjektiv deutlich besser beherrscht.Trotz erfreulicher Ergebnisse besteht in Teilbereichen noch Verbesserungspotenzial. Beispielsweise ist die Bewertung der Studierenden zur Frage nach der Vorbereitung auf die Behandlung von Schmerzpatienten noch nicht zufriedenstellend. Hier gilt es, das Curriculum mit Fokus auf die Kompetenzorientierung weiterzuentwickeln. Dabei können digitale Lehrformate ebenso integriert werden wie interprofessionelle Einheiten und Simulationspatienten. Zudem sind jedoch gleichzeitig auch die Prüfungsformate hin zu standardisierten praktischen Prüfungen weiterzuentwickeln.

Septic cardiomyopathy is a severe complication of sepsis and septic shock. This study aimed to evaluate the role of thrombomodulin and its lectin-like domain (LLD-TM) in the development of septic cardiomyopathy and the link between LLD-TM, HMGB-1, and toll-like receptors 2/4 (TLR 2/4) to intracellular mechanisms resulting in reduced cardiac function.Sepsis was induced using a polymicrobial peritoneal infection model in wildtype and mice lacking the lectin-like domain of thrombomodulin (TMLack of the LLD-TM results in a significant increase in severity of disease, decreased survival and impaired cardiac function in septic mice. In vivo and in vitro analyses of cardiomyocytes displayed high levels of inflammatory cytokines causing cardio-depression. In vitro results showed a strong correlation between elevated HMGB-1 levels and elevated troponin-1 levels. No connection was found between HMGB-1 and TLR-2 and/or -4 signalling pathways. Phospholamban mediated dysregulation of calcium homeostasis resulted in a general impairment after sepsis induction, but showed no connection to LLD-TM.Lack of LLD-TM results in an increase in general severity of disease, decreased survival and impaired cardiac function in sepsis. TLR-2 and TLR 4 do not participate as mediating factors in the development of septic cardiomyopathy.

As of late 2019, the COVID-19 pandemic has been a challenge to health care systems worldwide. Rapidly rising local COVID-19 incidence rates, result in demand for high hospital and intensive care bed capacities on short notice. A detailed up-to-date regional surveillance of the dynamics of the pandemic, precise prediction of required inpatient capacities of care as well as a centralized coordination of the distribution of regional patient fluxes is needed to ensure optimal patient care. In March 2020, the German federal state of Saxony established three COVID-19 coordination centers located at each of its maximum care hospitals, namely the University Hospitals Dresden and Leipzig and the hospital Chemnitz. Each center has coordinated inpatient care facilities for the three regions East, Northwest and Southwest Saxony with 36, 18 and 29 hospital sites, respectively. Fed by daily data flows from local public health authorities capturing the dynamics of the pandemic as well as daily reports on regional inpatient care capacities, we established the information and prognosis tool DISPENSE. It provides a regional overview of the current pandemic situation combined with daily prognoses for up to seven days as well as outlooks for up to 14 days of bed requirements. The prognosis precision varies from 21% and 38% to 12% and 15% relative errors in normal ward and ICU bed demand, respectively, depending on the considered time period. The deployment of DISPENSE has had a major positive impact to stay alert for the second wave of the COVID-19 pandemic and to allocate resources as needed. The application of a mathematical model to forecast required bed capacities enabled concerted actions for patient allocation and strategic planning. The ad-hoc implementation of these tools substantiates the need of a detailed data basis that enables appropriate responses, both on regional scales in terms of clinic resource planning and on larger scales concerning political reactions to pandemic situations.

Background The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. Methods We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. Results A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10− 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p

Background: Intraoperative hypotension is a common problem and direct or indirect sympathomimetic drugs are frequently needed to stabilize blood pressure. AkrinorTM consists of the direct and the indirect sympathomimetic noradrenaline and norephedrine. Both substances are covalently bound to the phosphodiesterase (PDE) inhibitor theophylline, yielding theodrenaline and cafedrine, respectively. We investigated pharmacodynamic effects of AkrinorTM and its constituents on contractile force and tension in human atrial trabeculae and internal A. mammaria rings. Methods: Isometric contractions were measured in human atrial trabeculae at 1 Hz and 37°C. CGP 20712A and ICI 118,551 were used to elaborate β1- and β2-adrenoceptor (AR) subtypes involved and phenoxybenzamine to estimate indirect sympathomimetic action. PDE-inhibition was measured as a potentiation of force increase upon direct activation of adenylyl cyclase by forskolin. Human A. mammaria preparations were used to estimate intrinsic vasoconstriction and impact on the noradrenaline-induced vasoconstriction. Results: Clinically relevant concentrations of AkrinorTM (4.2–420 mg/l) robustly increased force in human atrial trabeculae (EC50 41 ± 3 mg/l). This direct sympathomimetic action was mediated via β1-AR and the effect size was as large as with high concentrations of calcium. Only the highest and clinically irrelevant concentration of AkrinorTM increased the potency of forskolin to a minor extent. Norephedrine has lost its indirect sympathomimetic effect when bound to theophylline. Increasing concentrations of AkrinorTM (4.2–168 mg/l) alone did not affect the tension of human A. mammaria interna rings, but shifted the noradrenaline curve rightward from -logEC50 6.18 ± 0.08 to 5.23 ± 0.05 M. Conclusion: AkrinorTM increased cardiac contractile force by direct sympathomimetic actions and PDE inhibition, did not constrict A. mammaria preparations, but shifted the concentration-response curve to the right, compatible with an α-AR antagonistic effect or PDE inhibition. The pharmacodynamic profile and potency of AkrinorTM differs from noradrenaline and norephedrine in vitro. We anticipate metabolism of theodrenaline and cafedrine resulting in a different pharmacodynamic profile of AkrinorTM in vivo.

Heart failure is a common disease which is associated with an increased perioperative risk. In the following, we summarize pathophysiology, momentary treatment options and a preoperative approach to patients with heart failure.

A decreasing number of young physicians go for an academic career. The most frequently cited reasons are deficient structures and a lack of perspectives. The German Research Foundation warned against supply gaps in the medical sciences and in 2010 published recommendations for the improvement of professional development at all levels of medical education. A systematic survey of existing support tools and their dissemination among the medical societies has not yet been conducted.Network members of the AWMF were contacted by e-mail and asked to answer 59 questions regarding the support of junior scientists in their respective societies.28 out of 147 societies replied to the questionnaire. Most of the societies offer at least one of the following tools (multiple responses; selective topics): award for oral presentations (n=27), free attendance at conferences (n=15), financial research funding (n=19), assessment of any funding application (n=10), mentoring (n=6), support of students working on their doctoral thesis (n=26), support of studies abroad (n=16), training course on statistics/ laboratory methods (n=17), support with clinical studies (n=22).Here, we present our survey findings on established support tools for junior scientists for the first time. Apart from the medical schools, several medical-scientific societies have also started to provide tools of support for their junior scientists. However, to ensure that long-term perspectives and attractive conditions are provided in the field of medical science for junior scientists, broader support and interdisciplinary exchange of established tools are needed.

Our group has synthesized technetium-labeled fatty acids (FA) that are extracted into the myocardium and sequestered due to heart-type fatty acid binding protein (H-FABP) binding. In this article, we further address the detailed subcellular distribution and potential myocardial metabolism of [(99m)Tc]"4+1" FA.Experiments were conducted using isolated hearts of Wistar rats, as well as of wild-type and H-FABP(-/-) mice. Myocardium samples underwent subcellular fractionation [subsarcolemmal mitochondria (SM), intermyofibrillar mitochondria (IM), cytosol with microsomes, and nuclei and crude membranes] and analysis by thin-layer chromatography and high-performance liquid chromatography.The largest fraction of tissue radioactivity was associated with cytosol [79.69+/-8.88% of infused dose]. About 9.07+/-0.95% and 3.43+/-1.38% of the infused dose were associated with SM and IM fractions, respectively. In the rat heart, etomoxir, an inhibitor of carnitin-palmitoyl transferase I, did not significantly decrease radioactivity associated with mitochondrial fractions, whereas myocardial extraction of [(123)I]-labeled 15-(p-iodophenyl)-pentadecanoic acid (13.26% vs. 49.49% in controls) and the radioactivity associated with the SM and IM fractions were blunted. The percentage of the infused dose in the mitochondrial and crude fractions increased with the number of NH-amide groups of the FA derivative. Absence of H-FABP significantly decreased radioactivity count in the cytosolic fraction (P.001). No metabolic product of [(99m)Tc]"4+1" FA could be detected in any isolated heart.Myocardial [(99m)Tc]"4+1" FA extraction reflects binding to H-FABP and membrane structures (including the mitochondrial membrane). However, the compounds do not undergo mitochondrial metabolism because they do not reach the mitochondrial matrix.

(13)C, (18)F and (123)I fatty acids (FA) are used for myocardial imaging. Recently, our group showed that [(99m)Tc]-labeled "4+1" FA are extracted into the rat and guinea pig myocardium. The present study evaluates determinants of myocardial uptake and whole body biodistribution of these FA derivatives.Studies were performed with isolated perfused hearts of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with a FAT/CD36 deficiency, as well as with heart type FA binding protein knockout mice (H-FABP)(-/-) and H-FABP(+/+). Eight 4+1-(99m)Tc-FA were applied for 3 min followed by 1-min washout. A mathematical model was used to analyze FA dynamics and binding to proteins. Whole-body distribution was studied in rats with and without Tween 80. In vitro fractionation studies with [(99m)Tc]-FA assessed red blood cell uptake as well as association with plasma lipoproteins very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL).Myocardial extraction was 19.0-33.0% of the infused dose in isolated WKY and 15.2-26.4% in SHR hearts. However, H-FABP(-/-) showed a marked reduction of tracer extraction [2.8+/-0.6%ID (percent injected dose) vs. 17+/-2%ID P.001]. Uptake in red blood cells (1.2%ID) and incorporation into lipoproteins were negligible. Incubation of (99m)Tc-FA with albumin reduced ventricular extraction (P.001) into the range of established iodinated FA tracers. polyoxyethylene(20) sorbitan monooleate improved the heart-to-liver ratio in the biodistribution studies.Myocardial uptake of [(99m)Tc]-FA 4+1 derivatives is dependent on H-FABP. These substances may therefore provide a new tool to specifically assess regional myocardial changes of H-FABP.