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Mühlenfeld, Nils ; Vollrath, Jan Tilmann ; Hörauf, Jason-Alexander ; Schöffski, Oliver ; Sterz, Jasmina ; Riemenschneider, Julia ; Störmann, Philipp ; Marzi, Ingo ; Verboket, René
Hintergrund: Viele Patienten mit Bagatellverletzungen gehen heutzutage häufig vorschnell in die Notaufnahmen und binden dort Ressourcen und Personal.
Ziel der Arbeit: Das Erstellen des Kosten-Erlös-Verhältnis der ambulanten Versorgung von Bagatellverletzungen in der unfallchirurgischen Notaufnahme.
Material und Methoden: Die Kalkulation erfolgte anhand der einheitlich abgerechneten Notfallpauschalen des Einheitlichen Bemessungsmaßstabes (EBM). Mittels der gängigen Tarifverträge für Ärzte und Pflegepersonal wurden Minutenkosten berechnet. Der zeitliche Behandlungsaufwand wurde anhand von 100 Referenzpatienten mit einer Bagatellverletzung ermittelt. Die Fallkostenkalkulation mit den jeweilig anfallenden Ressourcen erfolgte mit dem operativen Controlling des Universitätsklinikums Frankfurt.
Ergebnisse: Eingeschlossen wurden 4088 Patienten mit Bagatellverletzungen, welche sich 2019 eigenständig fußläufig vorstellten. Die häufigsten Gründe für die Vorstellung waren Prellungen der unteren (31,9 %; n = 1303) und oberen Extremität (16,6 %; n = 677). Kalkuliert wurden Zeitaufwände von 166,7 min/Tag für das ärztliche und 213,8 min/Tag für das Pflegepersonal. Es wurde ein Gesamterlös von 29.384,31 € und Gesamtlosten von 69.591,22 € berechnet. Somit lässt sich ein Erlösdefizit von 40.206,91 € für das Jahr 2019 berechnen. Das entspricht einem monetären Defizit von 9,84 €/Patienten.
Diskussion: Es herrscht Knappheit an der medizinischen Ressource „Personal“, um das heutzutage hohe Aufkommen an sich selbst vorstellenden fußläufigen Patienten mit Bagatellverletzungen zufriedenstellend und ökonomisch zu bewältigen. Die bisherige Vergütung der Behandlung von Bagatellverletzungen durch den EBM ist für den Krankenhaussektor unzureichend.
Krambeck, Alexa ; Loth, Andreas German ; Leinung, Martin ; Syed-Ali, Anwar ; Filmann, Sonja Natalie ; Kramer, Sabine Maria ; Baumann, Uwe ; Stöver, Timo ; Diensthuber, Marc
Hintergrund und Fragestellung: Die Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)-Pandemie hat die Ausbildung von Medizinstudierenden grundlegend verändert. Die Notwendigkeit von Kontaktbeschränkungen und die damit einhergehende Forderung nach Distanzunterricht hat dazu geführt, dass innerhalb kurzer Zeit digitale Lehrformate umgesetzt werden mussten. Ziel dieser Arbeit war die Auswertung der studentischen Evaluationsergebnisse für virtuellen Unterricht im Fach Hals-Nasen-Ohren-Heilkunde während der SARS-CoV-2-Pandemie und ein Vergleich mit den zuvor erhobenen Evaluationsergebnissen unter Präsenzbedingungen.
Material und Methoden: Untersucht wurden die Evaluationsergebnisse für die Blockpraktika im Wintersemester 2020/21 und im Sommersemester 2021, die in einem virtuellen Format mit kurzer Präsenzphase durchgeführt wurden, sowie die der komplett im konventionellen Präsenzformat durchgeführten Praktika von Sommersemester 2018 bis Wintersemester 2019/20. Die anonyme Befragung der Studierenden bezog sich auf verschiedene Aspekte der Lehrveranstaltung, wie z. B. Organisation, Didaktik und Lernatmosphäre.
Ergebnisse: Von 16 abgefragten Kategorien zeigten 14 (87,5%) signifikant bessere Evaluationsergebnisse für die virtuellen Praktika verglichen mit den zuvor im Präsenzformat durchgeführten Praktika. Diese sehr positive Bewertung des digitalen Lehrangebots zeigte im Pandemieverlauf über die Dauer von zwei Semestern keine signifikante Änderung.
Schlussfolgerung: Die vorliegenden Daten belegen die hohe Akzeptanz eines digitalen Lehrangebots im Fach HNO-Heilkunde für Studierende. Auch wenn unerlässliche Bestandteile der ärztlichen Ausbildung, wie der Unterricht am Patienten und das Erlernen klinisch-praktischer Fertigkeiten, weiterhin nur im Präsenzformat realisiert werden können, legen die Ergebnisse nahe, dass digitale Elemente auch nach der SARS-CoV-2-Pandemie eine Rolle im Medizinstudium spielen könnten.
Tanneberger, Anna Maria ; Maawi, Sarah al- ; Herrera-Vizcaíno, Carlos ; Orlowska, Anna ; Kubesch, Alica ; Sader, Robert Alexander ; Kirkpatrick, Charles James ; Ghanaati, Shahram Michael
Objectives: The aim of the present study was to characterize the cellular reaction to a xenogeneic resorbable collagen membrane of porcine origin using a subcutaneous implantation model in Wistar rats over 30 days.
Materials and methods: Ex vivo, liquid platelet-rich fibrin (PRF), a leukocyte and platelet-rich cell suspension, was used to evaluate the blood cell membrane interaction. The material was implanted subcutaneously in rats. Sham-operated rats without biomaterial displayed physiological wound healing (control group). Histological, immunohistological, and histomorphometric analyses were focused on the inflammatory pattern, vascularization rate, and degradation pattern.
Results: The membrane induced a large number of mononuclear cells over the observation period, including lymphocytes, macrophages, and fibroblasts. After 15 days, multinucleated giant cells (MNGCs) were observed on the biomaterial surface. Their number increased significantly, and they proceeded to the center of the biomaterial on day 30. These cells highly expressed CD-68, calcitonin receptor, and MMP-9, but not TRAP or integrin-ß3. Thus, the membrane lost its integrity and underwent disintegration as a consequence of the induction of MNGCs. The significant increase in MNGC number correlated with a high rate of vascularization, which was significantly higher than the control group. Physiological wound healing in the control group did not induce any MNGCs at any time point. Ex vivo blood cells from liquid-PRF did not penetrate the membrane.
Conclusion: The present study suggests a potential role for MNGCs in biomaterial degradation and questions whether it is beneficial to accept them in clinically approved biomaterials or focus on biomaterials that induce only mononuclear cells. Thus, further studies are necessary to identify the function of biomaterial-induced MNGCs.
Clinical relevance: Understanding the cellular reaction to biomaterials is essential to assess their suitability for specific clinical indications and outline the potential benefit of specific group of biomaterials in the respective clinical indications.
Maurer-Grubinger, Christian ; Adjami, Frederic ; Avaniadi, Ioanna ; Christian, Wolfgang ; Doerry, Charlotte ; Fay, Viola Nathalie ; Fisch, Vanessa ; Gerez, Ali ; Goecke, Julian ; Kaya, Ugur ; Keller, Julia ; Krüger, Kai-Dominik ; Pflaum, Julia ; Porsch, Laurin ; Wischnewski, Christina ; Scharnweber, Benjamin ; Sosnov, Polyna ; Oremek, Gerhard ; Groneberg, Jan David Alexander ; Ohlendorf, Daniela Maren
Objectives: Symmetrical dental occlusion blocking is used in dentistry as a quick diagnostic tool to test for potential influences of the craniomandibular system on body sway and weight distribution. This study presents the changes of body sway and pressure distribution in healthy subjects, free of a temporomandibular dysfunction (TMD). Immediate effects between occlusal blocking and rest position on body sway and body weight distribution in general, as well as for both genders and for four age decades will be evaluated.
Materials and methods: 725 (396f/329 m) subjects (neither subjective signs of TMD nor acute/chronic complaints in the musculoskeletal system) volunteered (21 to 60 years) while both genders were divided into four age groups according to decades. A pressure measuring platform was used. Body sway and weight distribution were recorded in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking (bicuspid region) by cotton rolls.
Results: Both, the frontal sway and the sagittal sway reduced by 0.67 mm (t(724) = − 3.9 (p < 0.001)) and by 0.33 mm (t(724) = − 3.4 (p < 0.001)). The relative pressure under the left forefoot increased by 0.33% (t(724) = 2.88 (p < 0.001)) and the relative pressure overall under the forefoot increased by 0.67% (t(724) = − 3.4 (p < 0.001)). Gender-specific, age-specific and BMI-specific reactions could not be identified.
Conclusions: Subjects, free of any TMD and with no complaints of the musculoskeletal system, show small changes of the body sway and weight distribution when biting symmetrically on a cotton roll. These changes are independent of age, gender or body mass index (BMI). Due to the relative large sample size, the presented results can also be seen as norm values when body sway is used as an additional assessment of a TMD.
Wenzel, Mike ; Yu, Hang ; Uhlig, Annemarie ; Würnschimmel, Christoph ; Wallbach, Manuel ; Becker, Andreas ; Fisch, Margit ; Chun, Felix ; Meyer, Christian P. ; Leitsmann, Marianne
Purpose: To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function.
Methods: From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m2). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation.
Results: Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10–20), rates of eGFR < 60 ml/min/1.73m2 were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m2 in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m2. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2–1.3 mg/dl, when graphically depicted vs. postoperative CysC values (‘creatinine blind area’).
Conclusion: Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting.
Engler, Jennifer ; Güthlin, Corina ; Bertram, Laura ; Tesky, Valentina ; Schall, Arthur ; Joos, Stefanie ; Valentini, Jan
Objective: Our aim was to explore whether general practitioners (GPs) communicate with cancer patients on complementary and integrative medicine (CIM) in a patient-centred and case-specific manner.
Methods: We designed two cases of standardised breast cancer patients and allocated 29 GPs to hold a consultation either with Case 1 or Case 2. Case 1 presented with fears of possible physical side effects of hormone treatment. Case 2 feared a loss in social functioning because of nausea and emesis as possible side effects of chemotherapy. Consultations were audiotaped and analysed using the Roter Interaction Analysis System (RIAS). We analysed whether recommended CIM treatments and GPs' focus on psychosocial or medical and therapy-related content differed according to whether they were counselling Case 1 or Case 2.
Results: In consultations with Case 1, GPs rather focused on medical and therapy-related content and most often recommended mistletoe, diets and sports. In contrast, GPs focused on psychosocial content and they most often recommended methods of self-care when counselling Case 2.
Conclusion: The GPs in our sample reacted case-specifically to the patients' interest in CIM. Such responsive and patient-centred communication is a valuable resource but is often time-consuming. Adequate training and reimbursement should therefore be considered for GPs.
Sriha, Jessica ; Louis-Brennetot, Caroline ; Pierre-Eugène, Cécile ; Baulande, Sylvain ; Raynal, Virginie ; Kramdi, Amira ; Adameyko, Igor ; Ernsberger, Uwe ; Deller, Thomas ; Delattre, Olivier ; Janoueix-Lerosey, Isabelle ; Rohrer, Hermann
Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this question, we first set up cultures of mouse sympathetic neuroblasts and adrenal chromaffin cells. These cultures were then treated with various proliferation inhibitors to identify lineage-specific responses. We show that neuroblast and chromaffin cell proliferation was affected by WNT, ALK, IGF1, and PRC2/EZH2 signaling inhibitors to a similar extent. However, differential effects were observed in response to bromodomain and extraterminal (BET) protein inhibitors (JQ1, GSK1324726A) and to the CDK-7 inhibitor THZ1, with BET inhibitors preferentially affecting chromaffin cells, and THZ1 preferentially affecting neuroblasts. The differential dependence of chromaffin cells and neuroblasts on BET and CDK signaling may indicate different mechanisms during tumor initiation in sympathetic ganglia and adrenal.
Brünn, Robin ; Lemke, Dorothea ; Basten, Jale ; Kellermann-Mühlhoff, Petra ; Köberlein-Neu, Juliane ; Muth, Christiane ; Akker, Marjan van den
Polypharmacy is associated with a risk of negative health outcomes. Potentially inappropriate medications, interactions resulting from contradicting medical guidelines, and inappropriate monitoring, all increase the risk. This process evaluation (PE) of the AdAM study investigates implementation and use of a computerized decision-support system (CDSS). The CDSS analyzes medication appropriateness by including claims data, and hence provides general practitioners (GPs) with full access to patients’ medical treatments. We based our PE on pseudonymized logbook entries into the CDSS and used the four dimensions of the Medical Research Council PE framework. Reach, which examines the extent to which the intended study population was included, and Dose, Fidelity, and Tailoring, which examine how the software was actually used by GPs. The PE was explorative and descriptive. Study participants were representative of the target population, except for patients receiving a high level of nursing care, as they were treated less frequently. GPs identified and corrected inappropriate prescriptions flagged by the CDSS. The frequency and intensity of interventions documented in the form of logbook entries lagged behind expectations, raising questions about implementation barriers to the intervention and the limitations of the PE. Impossibility to connect the CDSS to GPs’ electronic medical records (EMR) of GPs due to technical conditions in the German healthcare system may have hindered the implementation of the intervention. Data logged in the CDSS may underestimate medication changes in patients, as documentation was voluntary and already included in EMR.
Köllermann, Jens ; Höh, Robert Benedikt ; Ruppel, Daniel ; Smith, Kevin ; Reis, Henning ; Wenzel, Mike ; Preißer, Felix Martin ; Kosiba, Marina ; Mandel, Philipp ; Karakiewicz, Pierre I. ; Becker, Andreas ; Chun, Felix ; Wild, Peter Johannes ; Kluth, Luis
The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium–aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1–38) vs. a median of 15 (range 2–74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.
Background: Some studies suggest a mood-congruent attentional bias in bipolar patients. However, for euthymic patients, especially in dependence on the predominant polarity, there is little and inconsistent data. A clearer understanding of emotion-related attentional biases and their relationship to dysfunctional emotion regulation could help improving the diagnostics and treatment of bipolar disorder (BD). Twenty bipolar patients in a depressive state (BP-acute-D), 32 euthymic patients with manic (BP-euth-M) or depressive (BP-euth-D) predominant polarity, and 20 healthy control participants (HC) performed a dot-probe task (DPT) with happy and sad faces presented for 250 ms or 1250 ms in two different runs. Emotion regulation strategies were assessed with two questionnaires.
Results: In the short presentation condition of the DPT, BP-euth-M showed less attention for happy faces than HC (p = .03, r = − 0.48). BP-acute-D scored lower in cognitive reappraisal and putting into perspective and higher in suppression, catastrophizing, and rumination than HC. BP-euth-M scored higher in rumination and BP-euth-D lower in putting into perspective and higher in catastrophizing than HC. In BP-euth-D and HC, bias scores for sad faces in the longer presentation condition and reappraisal scores correlated positively.
Conclusions: Results of the DPT suggest an avoidance of happy faces for BP-euth-M which we interpret as a protection mechanism for triggers of mania. That individuals who apply more reappraisal show more selective attention to sad faces could on the one hand reflect a mental effort in reevaluating the sad emotional input and on the other hand a greater tolerance for it.
Nowotny, Hanna ; Neumann, Uta ; Tardy-Guidollet, Véronique ; Ahmed, S. Faisal ; Baronio, Federico ; Battelino, Tadej ; Bertherat, Jérôme ; Blankenstein, Oliver ; Bonomi, Marco ; Bouvattier, Claire ; Brac de la Perrière, Aude ; Brucker, Sara ; Cappa, Marco ; Chanson, Philippe ; Claahsen-van der Grinten, Hedi L. ; Colao, Annamaria ; Cools, Martine ; Davies, Justin H. ; Dörr, Helmuth-Günther ; Fenske, Wiebke Kristin ; Ghigo, Ezio ; Giordano, Roberta ; Gravholt, Claus H. ; Huebner, Angela ; Husebye, Eystein Sverre ; Igbokwe, Rebecca ; Juul, Anders ; Kiefer, Florian ; Léger, Juliane ; Menassa, Rita ; Meyer, Gesine ; Neocleous, Vassos ; Phylactou, Leonidas A. ; Rohayem, Julia ; Russo, Gianni ; Scaroni, Carla ; Touraine, Philippe ; Unger, Nicole ; Vojtková, Jarmila ; Yeste, Diego ; Lajic, Svetlana ; Reisch, Nicole
Objective: To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency.
Design and methods: A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN.
Results: Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4–5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France.
Conclusions: This study reveals a high international variability and discrepancy in the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence-based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH.
Relationship between regional white matter hyperintensities and alpha oscillations in older adults
(2021)
Kumral, Deniz ; Cesnaite, Elena ; Beyer, Frauke ; Hofmann, Simon M. ; Hensch, Tilman ; Sander, Christian ; Hegerl, Ulrich ; Haufe, Stefan ; Villringer, Arno ; Witte, A. Veronica ; Nikulin, Vadim V.
Aging is associated with increased white matter hyperintensities (WMHs) and with alterations of alpha oscillations (7–13 Hz). However, a crucial question remains, whether changes in alpha oscillations relate to aging per se or whether this relationship is mediated by age-related neuropathology like WMHs. Using a large cohort of cognitively healthy older adults (N = 907, 60–80 years), we assessed relative alpha power, alpha peak frequency, and long-range temporal correlations from resting-state EEG. We further associated these parameters with voxel-wise WMHs from 3T MRI. We found that a higher prevalence of WMHs in the superior and posterior corona radiata as well as in the thalamic radiation was related to elevated alpha power, with the strongest association in the bilateral occipital cortex. In contrast, we observed no significant relation of the WMHs probability with alpha peak frequency and long-range temporal correlations. Finally, higher age was associated with elevated alpha power via total WMH volume. We suggest that an elevated alpha power is a consequence of WMHs affecting a spatial organization of alpha sources.
Middeke, Jan Moritz ; Metzeler, Klaus Hans ; Röllig, Christoph ; Krämer, Michael ; Eckardt, Jan-Niklas ; Stasik, Sebastian ; Greif, Philipp ; Spiekermann, Karsten ; Rothenberg-Thurley, Maja ; Krug, Utz ; Braess, Jan ; Krämer, Alwin ; Hochhaus, Andreas ; Brümmendorf, Tim Henrik ; Naumann, Ralph ; Steffen, Björn ; Einsele, Hermann ; Schaich, Markus ; Burchert, Andreas ; Neubauer, Andreas ; Görlich, Dennis ; Sauerland, Cristina ; Schäfer-Eckart, Kerstin ; Schliemann, Christoph ; Krause, Stefan W. ; Hänel, Mathias ; Frickhofen, Norbert ; Noppeney, Richard ; Kaiser, Ulrich ; Kaufmann, Martin ; Kunadt, Désirée ; Wörmann, Bernhard ; Sockel, Katja ; Bonin, von Malte ; Herold, Tobias ; Müller-Tidow, Carsten ; Platzbecker, Uwe ; Berdel, Wolfgang E. ; Serve, Hubert ; Baldus, Claudia ; Ehninger, Gerhard ; Schetelig, Johannes ; Hiddemann, Wolfgang ; Bornhäuser, Martin ; Stölzel, Friedrich ; Thiede, Christian
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
Zöllner, Johann Philipp ; Grau, Janina ; Rosenow, Felix ; Sauter, Matthias ; Knuf, Markus ; Kurlemann, Gerhard ; Mayer, Thomas ; Hertzberg, Christoph ; Bertsche, Astrid ; Immisch, Ilka ; Klein, Karl Martin ; Knake, Susanne ; Marquard, Klaus ; Meyer, Sascha ; Noda, Anna ; Podewils, Felix von ; Schäfer, Hannah ; Thiels, Charlotte ; Willems, Laurent Maximilian ; Zukunft, Bianca ; Schubert-Bast, Susanne ; Strzelczyk, Adam
Background: Tuberous sclerosis complex (TSC) is a monogenetic, multisystem disorder characterized by benign growths due to TSC1 or TSC2 mutations. This German multicenter study estimated the costs and related cost drivers associated with organ manifestations in adults with TSC.
Methods: A validated, three-month, retrospective questionnaire assessed the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket (OOP), and nursing care-level costs among adult individuals with TSC throughout Germany from a societal perspective (costing year: 2019).
Results: We enrolled 192 adults with TSC (mean age: 33.4 ± 12.7 years; range: 18–78 years, 51.6% [n = 99] women). Reported TSC disease manifestations included skin (94.8%) and kidney and urinary tract (74%) disorders, epilepsy (72.9%), structural brain defects (67.2%), psychiatric disorders (50.5%), heart and circulatory system disorders (50.5%), and lymphangioleiomyomatosis (11.5%). TSC1 and TSC2 mutations were reported in 16.7% and 25% of respondents, respectively. Mean direct health care costs totaled EUR 6452 (median EUR 1920; 95% confidence interval [CI] EUR 5533–7422) per patient over three months. Medication costs represented the major direct cost category (77% of total direct costs; mean EUR 4953), and mechanistic target of rapamycin (mTOR) inhibitors represented the largest share (68%, EUR 4358). Mean antiseizure drug (ASD) costs were only EUR 415 (6%). Inpatient costs (8%, EUR 518) and outpatient treatment costs (7%; EUR 467) were important further direct cost components. The mean care grade allowance as an approximator of informal nursing care costs was EUR 929 (median EUR 0; 95% CI EUR 780–1083) over three months. Mean indirect costs totaled EUR 3174 (median EUR 0; 95% CI EUR 2503–3840) among working-age individuals (< 67 years in Germany). Multiple regression analyses revealed mTOR inhibitor use and persistent seizures as independent cost-driving factors for total direct costs. Older age and disability were independent cost-driving factors for total indirect costs, whereas epilepsy, psychiatric disease, and disability were independent cost-driving factors for nursing care costs.
Conclusions: This three-month study revealed substantial direct healthcare, indirect healthcare, and medication costs associated with TSC in Germany. This study highlights the spectrum of organ manifestations and their associated treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.
Wiercinska, Eliza ; Schlipfenbacher, Vera Barbara Franziska ; Bug, Gesine ; Bader, Peter ; Verbeek, Mareike ; Seifried, Erhard ; Bönig, Halvard-Björn
Background: Because of limitations of transportation imposed by the COVID-19 pandemic, current recommendation calls for cryopreservation of allogeneic stem cell transplants before patient conditioning. A single cell therapy laboratory was selected to function as the central cryopreservation hub for all European registry donor transplants intended for the Australian-Pacific region. We examined properties of these transplants to ascertain how quality is maintained.
Methods: We analyzed 100 pandemic-related allogeneic mobilized blood-derived stem cell apheresis products generated at 30 collection sites throughout Europe, shipped to and cryopreserved at our center between April and November of 2020. Products were shipped in the cool, subsequently frozen with DMSO as cryoprotectant. Irrespective of origin, all products were frozen within the prescribed shelf-life of 72 h.
Results: Prior to cryopreservation, viable stem cell and leukocyte count according to the collection site and our reference laboratory were highly concordant (r2 = 0.96 and 0.93, respectively) and viability was > 90% in all instances. Median nominal post-thaw recovery of viable CD34+ cells was 42%. Weakly associated with poorer CD34+ cell recovery was higher leukocyte concentration, but not time lag between apheresis or addition of cryopreservant, respectively, and start of freezing. The correlation between pre- and post-thaw CD34+ cell dose was high (r2 = 0.85), hence predictable. Neutrophil and platelet engraftment were prompt with no evidence of dose dependency within the range of administered cell doses (1.31–15.56 × 106 CD34+ cells/kg).
Conclusions: General cryopreservation of allogeneic stem cell transplants is feasible. While more than half of the CD34+ cell content is lost, the remaining stem cells ensure timely engraftment.
Rappl, Peter ; Rösser, Silvia ; Maul, Patrick ; Bauer, Rebekka ; Huard, Arnaud ; Schreiber, Yannick ; Thomas, Dominique ; Geisslinger, Gerd ; Jakobsson, Per-Johan ; Weigert, Andreas ; Brüne, Bernhard ; Schmid, Tobias
Despite the progress to understand inflammatory reactions, mechanisms causing their resolution remain poorly understood. Prostanoids, especially prostaglandin E2 (PGE2), are well-characterized mediators of inflammation. PGE2 is produced in an inducible manner in macrophages (Mϕ) by microsomal PGE2-synthase-1 (mPGES-1), with the notion that it also conveys pro-resolving properties. We aimed to characterize the role of mPGES-1 during resolution of acute, zymosan-induced peritonitis. Experimentally, we applied the mPGES-1 inhibitor compound III (CIII) once the inflammatory response was established and confirmed its potent PGE2-blocking efficacy. mPGES-1 inhibition resulted in an incomplete removal of neutrophils and a concomitant increase in monocytes and Mϕ during the resolution process. The mRNA-seq analysis identified enhanced C-X3-C motif receptor 1 (CX3CR1) expression in resident and infiltrating Mϕ upon mPGES-1 inhibition. Besides elevated Cx3cr1 expression, its ligand CX3CL1 was enriched in the peritoneal lavage of the mice, produced by epithelial cells upon mPGES-1 inhibition. CX3CL1 not only increased adhesion and survival of Mϕ but its neutralization also completely reversed elevated inflammatory cell numbers, thereby normalizing the cellular, peritoneal composition during resolution. Our data suggest that mPGES-1-derived PGE2 contributes to the resolution of inflammation by preventing CX3CL1-mediated retention of activated myeloid cells at sites of injury.
Einleitung: Knochenersatzmaterialien gewinnen in der regenerativen Medizin immer weiter an Bedeutung. Polylactid-co-Glycolid (PLGA) wird als etabliertes synthetisches Biomaterial bereits vielseitig in der medizinischen Versorgung eingesetzt, häufig in Form von Mikropartikeln oder Platzhaltern beladen mit Antibiotika oder immunaktiven Zellen zur topischen Antibiotikatherapie und Freisetzung von regenerativen Zellen in einer Defektzone. Ziel dieser Studie war die Charakterisierung einer neuen Darbietungsform von PLGA auf ihre physikalischen Eigenschaften, ihre immunologische Signatur und Zytokompatibilität. Dieses Material soll den Einsatz von PLGA in Form einer porösen Membran zur Abdeckung von großen Knochendefekten ermöglichen.
Material und Methoden: Das PLGA-Gemisch wurde in Form von scheibenförmigen Prüfkörpern und Membranen aufbereitet. Es wurde eine biomechanische Analyse des Materials auf Bruchfestigkeit, Biegesteifigkeit und seine Diffusionskapazität durchgeführt. Die Scaffolds wurden mit Knochenmarkstammzellen (BMC und MSC) besiedelt. Mittels MTT-Tests wurde die Lebensdauer und die Viabilität der Zellen auf der Prüfkörperoberfläche ermittelt. Die Zellen wurden durch PCR-Analyse auf osteogene Differenzierung untersucht. Zur Erfassung der immunologischen Signatur erfolgte ein Vollblutstimulationstest mit anschließender umfassender Auswertung des Sekretoms mittels Proteom Profiler-Analyse.
Ergebnisse: Das Material wies eine geringe mechanische Stabilität auf. Die PLGA-Membran zeigte sich für Proteine bis 11,4 kDa durchlässig. Es konnte eine stetige Degeneration des Materials in wässrigem Milieu festgestellt werden. In der Sekretom-Analyse des Vollblutstimulationstests zeigte sich eine für die PLGAMembran charakteristische immunologische Signatur mit Aktivierung von proinflammatorischen Faktoren. Das Zellüberleben auf der Prüfkörperoberfläche nahm während des Erfassungszeitraums konstant ab, während die Zellviabiliät auf dem Wellboden stieg. Es konnte keine signifikante osteogene Differenzierung der Stammzellen festgestellt werden.
Diskussion: Die schnelle Degeneration des Materials in wässriger Umgebung beeinflusste sowohl die Stabilität der Membran als auch die Zelladhäsion auf den Scaffolds negativ. Das Material wirkte dabei weder toxisch auf die Zellen, noch induzierte es eine osteogene Differenzierung. Die Analyse der Immunsignatur ließ eine frühe und starke Entzündungsreaktion nach Implantation des Materials vermuten.
Schlussfolgerung und Ausblick: Während das vorgelegte PLGA-Gemisch nicht die mechanischen Eigenschaften eines gewichttragenden Knochenersatzstoffes aufweist, so lässt es sich dennoch erfolgreich mit Stammzellen beladen, die nach Implantation gezielt in der Defektzone freigesetzt werden können. Die Anregung einer starken Immunantwort kann gerade in der frühen Heilungsphase hilfreich sein. Weitere in vivo-Untersuchungen am Tiermodell sind notwendig zur Optimierung möglicher therapeutischer Anwendungen.
Weingärtner, Karoline Maj ; Störmann, Philipp ; Schramm, David ; Wutzler, Sebastian ; Zacharowski, Kai ; Marzi, Ingo ; Lustenberger, Thomas
Background: Every year, ~ 210,000 initial implantations of hip endoprostheses are carried out in Germany alone. The “bone cement implantation syndrome” (BCIS) is considered a severe peri- and early-postoperative complication when implanting cemented prostheses. The origin of the BCIS and its impact on the clinical outcome are still uncertain. This study investigates the clinical progression after BCIS cases in patients with cemented hemiarthroplasty. Risk factors for the occurrence of BCIS are evaluated.
Material and methods* Clinical data of all patients with a proximal femur fracture and which received a cemented hemiarthroplasty within a period of 9.5 years have been collected. BCIS (+) patients and BCIS (−) patients were compared with respect to their demographics and clinical outcome. Risk factors for the development of BCIS were identified.
Results: A total of 208 patients could be included with complete data sets. The mean age was 81.1 ± 10.0 years. Overall, 37% of the patients showed symptoms of BCIS. In comparison to BCIS (−) patients there was a significantly higher rate of cardiovascular complications (27.3% vs. 13.7%, p = 0.016) and a higher in-hospital mortality rate (15.6% vs. 4.6%, p = 0.006) in BCIS (+) patients. Age, absence of a femoral borehole and ASA status were identified as statistically significant risk factors of BCIS.
Conclusion: BCIS is frequently observed and in some cases severe complication. The therapy is exclusively symptomatic; identifying preventional measures might reduce the occurrence of BCIS.
Hintergrund: Die Erstversorgung von Wunden und kleinere chirurgische Eingriffe gehören neben der hochspezialisierten Medizin zu den allgemein notwendigen Grundleistungen der Notfallversorgung in den Kliniken. Die Vergütung der ambulanten Notfallleistungen für gesetzlich Versicherte erfolgt derzeit nach dem Einheitlichen Bewertungsmaßstab (EBM), welchem die betriebswirtschaftliche Aufwandserfassung des niedergelassenen Sektors als Kalkulationsgrundlage dient. Krankenhäuser haben im Vergleich zu Arztpraxen wesentlich höhere Vorhaltungskosten.
Ziel der Arbeit: In dieser Arbeit wird das entstehende Kosten-Erlös-Verhältnis der ambulanten Wundversorgung in einer Notaufnahme durch die Vergütung nach EBM analysiert.
Material und Methoden: Die Daten wurden in der Notaufnahme des Universitätsklinikums Frankfurt am Main über 12 Monate erhoben. Eingeschlossen wurden alle Patienten, die in diesem Zeitraum eine Wundversorgung mittels Naht erhielten. Die Kosten wurden der Abrechnung nach EBM 01210 (bzw. 01212) mit der Zusatzpauschale für kleinchirurgische Eingriffe EBM 02301 gegenübergestellt.
Ergebnisse: Im Beobachtungszeitraum wurden 1548 Patienten versorgt; das entspricht 19,52 % aller unfallchirurgischen Fälle. Den Kosten einer Standardwundversorgung in Höhe von 45,40 € steht eine Vergütung von 31,83 € gegenüber. Die Berechnung des Gesamterlöses weist einen Defizitbetrag von 13,57 € pro ambulantem Fall auf; dies entspricht einem Jahresdefizit von 21.006,36 €.
Diskussion: Es konnte gezeigt werden, dass ohne Betrachtung der relevanten Vorhaltekosten in keinem Fall eine Kostendeckung erreicht werden kann.
Die bisherige Vergütung der ambulanten Wundversorgung nach EBM erscheint unzureichend. Eine Anpassung bzw. Zusatzvergütung scheint notwendig, um eine ausreichende Versorgungsqualität in Zukunft sicherstellen zu können.