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Savigny, Clara von ; Juratli, Mazen A. ; Koch, Christine ; Gruber-Rouh, Tatjana ; Bechstein, Wolf Otto ; Schreckenbach, Teresa
Aim: The reversal of diverting loop ileostomy (DLI) is one of surgical trainees’ first procedures. Complications of DLI reversal can cause life-threatening complications and increase patient morbidity. This study compared DLI reversals performed by surgical trainees with those by attending surgeons.
Method: This retrospective cohort study was performed at a single primary care center on 300 patients undergoing DLI reversal. The primary outcome was morbidity, according to the Clavien-Dindo classification (CDC), with special attention paid to the surgeon’s level of training. The secondary endpoint was postoperative intestinal motility dysfunction.
Results: Surgical trainees had significantly longer operation times (p < 0.001) than attending surgeons. Univariate analyses revealed no influence on the level of training for postoperative morbidity. First bowel movement later than 3 days after surgery was a significant risk factor for CDC 3 (OR, 4.348; 96% CI, 1670–11.321; p = 0.003). Independent risk factors for surgical site infections (SSIs) were an elevated BMI (OR, 1.162; 95% CI, 1.043–1.1294; p = 0.007) and a delayed bowel movement (OR, 3.973; 95% CI, 1.300–12.138; p = 0.015). For postoperative intestinal motility dysfunction, an independent risk factor was a primary malignant disease (OR, 1.980; 95% CI, 1.120–3.500; p = 0.019), and side-to-side stapled anastomosis was a protective factor (OR, 0.337; 95% CI 0.155–0.733; p = 0.006).
Conclusion: Even though surgical trainees needed significantly more time to perform the surgery, the level of surgical training was not a risk factor for increased postoperative morbidity. Instead, delayed first bowel movement was predictive of SSI.
When skeletal remains are found, professionals try to identify the deceased. Specialists, i.e. forensic osteologists, forensic pathologists and anthropologists, are trained in the identification process and answer questions of human specificity, postmortem interval, individual features such as sex, age, height and ethnic origin, as well as signs of injury. Different imaging techniques can aid in the identification process. Further, there is a widely used computer software, Fordisc®, published by Stephen Ousley and Richard Jantz that uses discriminant function analysis for the classification of unknown skeletal remains regarding sex, ancestry and body height. It uses, among others, information from the Forensic Anthropology Data Bank (FDB), which is a centralized database with contemporary skeletal data from identified forensic cases. However, the applicability of Fordisc® to other populations than North America is questionable. In the past, scientists have expressed a desire for a European equivalent of the FDB or an update with a European reference sample. In order to generate a European reference sample, cranial and postcranial measurements must be collected from identified skeletal remains. This can be done either with an analog measuring technique, formed by anthropologists, or, as research has introduced, digitally. Other studies have already investigated whether classical osteometric measurements can be reconstructed and applied from post-mortem computed tomography scans. Digital osteology could be the key to generating a European reference sample more efficiently and without legal issues.
In this study, the two different methods were used to take craniometric measurements of 25 skulls. An analog and a digital measuring technique were applied to cranial and mandibular measurements, as used by the Forensic Data Bank Forms by Fordisc®. For the digital measuring technique, the skulls were first scanned with a computed tomography scanner and underwent 3D-reconstruction. The data collected from the two independent analog and digital measurements was statistically analyzed by “Comparison of multiple methods” and visualized with Bland & Altman plots. Of all the 39 measurements, 31 measurements showed a mean difference up to ±2 mm, which is the generally accepted error in an anthropological setting. Most of the measurements, which were not within the accepted error, utilized projection points in the 3D reconstructed image to measure landmarks. The statistical analysis showed significant proportional differences in 13 measurements (p<0,05). Further, the percentage errors were determined: most of the measurements had a median percentage error of < 3%, 17 of the 39 measurements had a median of < 1,5%.
This study shows that the following measurements of the Forensic Data Bank could possibly be used to collect digital cranial osseous data with a deviation of ≥- 2 mm to ≤ 2 mm: GOL, XCB, ZYB, BPL, MAB, AUB, UFHT, WFB, UFBR, NLH, NLB, OBB left, OBH right, OBH left, EKB, DKB, FRC, PAC, FOL, FOB, ASB, ZMB, MOW, HMF right, HMF left, TMF left, TMF right, GOG, CDB, WRB right, WRB left. Taking the percentage error into consideration, it is not clear whether all the measurements with an acceptable deviation still fulfill the requirements for digital data collection. Depending on the interpretation of the median percentage error, 24 to 31 accurate measurements were identified, which can possibly be used to generate a necessary reference sample from 3D reconstructed CT images for the Forensic Data Bank. This is something researchers have been asking for, as the quality of the results, when using Fordisc®, is population dependent. Nevertheless, research should continue concerning generally accepted percentage differences or errors in a digital setting, since the meaning of an accepted 2 mm deviation in anthropology, remains unclear.
Koschade, Sebastian E. ; Stratmann, Jan Alexander ; Steffen, Björn ; Shaid, Shabnam ; Finkelmeier, Fabian ; Serve, Hubert ; Miesbach, Wolfgang ; Brandts, Christian Hubertus ; Ballo, Olivier
Objectives and methods: Venous thromboembolic (VTE) events are emerging as frequent complications in acute myeloid leukemia (AML); however, there is insufficient data regarding epidemiology, risk factors, and impact on outcomes. The optimal approach to balance risks of thrombosis and hemorrhage remains unclear. This retrospective single-center study in AML patients undergoing induction chemotherapy between 2007 and 2018 assessed incidence, risk factors, features, and outcomes of early-onset VTE.
Results: 423 patients (median age 59 years) were enrolled. VTE was diagnosed in 31 patients (7.3%) within 3 months of admission. The median time to VTE was 3 days. Non-central venous catheter (CVC)-related VTE occurred in 19 patients (61%). Main risk factor for VTE was leukocytosis at admission, independent of platelet counts/INR. Four patients (13%) exhibited VTE recurrence. No deaths directly related to VTE or major bleeding events associated with platelet-adjusted anticoagulation in patients with VTE were recorded. There was no clear impact of VTE on 1-year overall survival; however, non-CVC-related VTE may be associated with adverse outcomes.
Conclusions: Early-onset VTE is a common complication in newly diagnosed AML patients admitted for induction chemotherapy. Leukocytosis is an independent VTE risk factor. The potentially adverse impact of non-CVC-related VTE merits further study.
Mende, Hannah ; Khatri, Anshu ; Lange, Carolin ; Poveda-Cuevas, Sergio Alejandro ; Tascher, Georg ; Covarrubias-Pinto, Adriana ; Löhr, Frank ; Koschade, Sebastian E. ; Đikić, Ivan ; Münch, Christian ; Bremm, Anja ; Brunetti, Lorenzo ; Brandts, Christian Hubertus ; Uckelmann, Hannah Julia ; Dötsch, Volker ; Rogov, Vladimir V. ; Bhaskara, Ramachandra M. ; Müller, Stefan
Highlights
• NPM1/NPM1c induce the autophagy-lysosome pathway by activating the master regulator TFEB
• NPM1/NPM1c bind to GABARAP proteins via an atypical module in their N-terminal regions
• The pro-autophagic activity of NPM1c depends on this GABARAP binding module
Summary
The nucleolar scaffold protein NPM1 is a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. NPM1 mutations, known as NPM1c variants promoting its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark of AML cells is their dependency on elevated autophagic flux. Here, we show that NPM1 and NPM1c induce the autophagy-lysosome pathway by activating the master transcription factor TFEB, thereby coordinating the expression of lysosomal proteins and autophagy regulators. Importantly, both NPM1 and NPM1c bind to autophagy modifiers of the GABARAP subfamily through an atypical binding module preserved within its N terminus. The propensity of NPM1c to induce autophagy depends on this module, likely indicating that NPM1c exerts its pro-autophagic activity by direct engagement with GABARAPL1. Our data report a non-canonical binding mode of GABARAP family members that drives the pro-autophagic potential of NPM1c, potentially enabling therapeutic options.
Schubert, Leonie ; Naujoks, Frank ; Störmann, Philipp ; Rüsseler, Miriam ; Herrmann, Eva ; Chobotsky, Holger ; Marzi, Ingo ; Wagner, Nils
Hintergrund: Ein steigendes Einsatzaufkommen lässt sich sowohl im Rettungsdienst als auch im notärztlichen System in Deutschland verzeichnen. Oft werden dabei Fehleinsätze durch leicht erkrankte/verletzte Patienten als wachsende Problematik vermutet. Die vorliegende Untersuchung überprüft die Hypothese von steigenden Einsatzzahlen mit gleichzeitiger Zunahme von gegebenenfalls nichtindizierten Einsätzen.
Material und Methoden: Es erfolgte eine retrospektive Analyse der notärztlichen Einsätze des an der Universitätsklinik Frankfurt am Main stationierten Notarzteinsatzfahrzeugs von 2014 bis 2019. Die Analyse berücksichtigt zudem Faktoren wie die notärztliche Tätigkeit, Behandlungspriorität, Alarmierungsart und das Patientenalter.
Ergebnisse: Im beobachteten Zeitraum lässt sich ein Anstieg der notärztlichen Einsatzzahlen um mehr als 20 % erkennen. Der größte Anstieg zeigt sich bei Einsätzen, bei denen keine notärztliche Tätigkeit (+80 %) notwendig war. Einsätze der niedrigsten Behandlungspriorität (+61 %) sowie der höchsten Behandlungspriorität (+61 %) nahmen ebenfalls signifikant zu.
Diskussion: Die vorliegenden Zahlen stützen die Hypothese, dass bei signifikant gesteigertem Einsatzaufkommen mehr Einsätze durch den Notarzt bewältigt werden müssen, bei denen er rückblickend nicht notwendig gewesen wäre. Trotzdem gibt es auch mehr Patienten, die einen sofortigen Arztkontakt benötigen. Die hieraus resultierende erhöhte Einsatzfrequenz kann zu einer erhöhten Belastung sowie erschwerten zeitgerechten Disposition der notärztlichen Ressource führen.
Bei polytraumatisierten Patienten hat das Thoraxtrauma einen großen Einfluss auf den weiteren Verlauf und die Prognose der schwerverletzten Patienten. In verschiedenen Untersuchungen konnte bereits gezeigt werden, dass Interleukin-6 bei Traumata oder Gewebeschäden durch geplante Operationen vermehrt auftritt und dass vor allem bei Verletzungen des Thorax im Vergleich zu anderen Organen und Geweben ein deutlich höherer IL-6-Wert messbar ist.
In der vorliegenden retrospektiven Studie wurde bei einem Patientenkollektiv mit vergleichbarer Verletzungsschwere untersucht, ob eine Korrelation zwischen der Höhe des initialen IL-6-Wertes und der Komplikationsentwicklung nach schwerem isolierten Thoraxtrauma nachzuweisen ist und dadurch ein höherer IL-6-Wert im Schockraum mit einem erhöhten Risiko für Lungenversagen assoziiert ist.
Hierbei wurden insgesamt 62 Patienten mit einem AISThorax ≥ 3 und einem AIS-Wert <3 bezogen auf alle anderen Organsysteme untersucht, die zwischen dem 01.01.2015 und dem 31.12.2018 über den traumatologischen Schockraum des Universitätsklinikums Frankfurt aufgenommen wurden. Die Datenerhebung über den weiteren Verlauf wurde bis zehn Tage nach Aufnahme über die klinikinterne Dokumentation und das Traumaregister® der DGU ausgewertet. Betrachtet wurden hierbei der Verlauf der IL-6-Werte sowie präklinische und klinische Vitalparameter und klinische Parameter wie die Dauer des Intensivaufenthaltes, die Beatmungspflichtigkeit und Komplikationen wie die Entwicklung einer Pneumonie. Die Patienten wurden retrospektiv nach dem schlechtesten Horovitz-Quotienten in zwei Gruppen eingeteilt. Zehn Patienten zeigten einen Horovitz-Index < 200mmHg und wurden der Gruppe ‚Organversagen Lunge Ja‘ zugeteilt, die übrigen 52 Patienten mit einem Horovitz-Index ≥ 200mg wurden der Gruppe ‚Organversagen Lunge Nein‘ zugewiesen. In den beiden Gruppen zeigte sich vor allem bei Aufnahme in den Schockraum sowie einen Tag danach ein signifikanter Unterschied der IL-6-Werte mit einem IL-6 von 1171,2 ± 2879,7 pg/ml bei Aufnahme sowie 491,3 ± 662,0 pg/ml am ersten Tag nach Aufnahme in die Klinik in der Gruppe ‚Organversagen Lunge Ja‘. Demgegenüber wiesen die Patienten in der Gruppe ‚Organversagen Lunge Nein‘ einen signifikant geringeren IL-6-Wert mit 168,7 ± 279,3 pg/ml bei Aufnahme in den Schockraum sowie 120,0 ± 136,3 pg/ml am ersten Tag nach Aufnahme auf. Der schwerere Verlauf des Thoraxtraumas zeigte sich deutlich in der Gruppe ‚Organversagen Lunge Ja‘: Neben einer initialen Beatmungspflicht von 100 % im Gegensatz zu 36,5 % der Patienten der Gruppe ‚Organversagen Lunge Nein‘ konnte auch hier eine signifikant höhere Rate von Reintubationen, Tracheotomien und Pneumonien bei deutlich längerer Zeit der invasiven Beatmung festgestellt werden. Auch die gesamte Verweildauer auf der Intensivstation war dementsprechend in der Gruppe ‚Organversagen Lunge Ja‘ mit 16,2 ± 9,0 Tagen deutlich länger als in der Gruppe ‚Organversagen Lunge Nein‘ (6,7 ± 6,5 Tage). Insgesamt bestätigen die vorliegenden Daten, dass mit einem initial erhöhten gemessenen IL-6 ein gesteigertes Risiko einhergeht, ein Lungenversagen zu entwickeln.
Drosos, Ioannis ; De Rosa, Roberta ; Cremer, Sebastian ; Seppelt, Philipp ; Hemmann, Katrin ; Oppermann, Jana ; Blessing, Recha Ruth Liselotte ; Mas-Peiro, Silvia ; Vasa-Nicotera, Mariuca ; Zeiher, Andreas M. ; Dimitriadis, Zisis
Background: Percutaneous left atrial appendage occlusion (LAAO) represents an alternative stroke prevention method in patients with atrial fibrillation and an increased bleeding risk, chronic kidney disease or contraindications to oral anticoagulants. Aim of our study was to evaluate the feasibility and safety of percutaneous LAAO in high-risk, frail patients having undergone transcatheter aortic valve implantation (TAVI).
Methods: Thirty-one patients having undergone TAVI and scheduled for LAAO were prospectively included in our study.
Results:Implantation was successful in 29 of 31 cases (93.5%).There were no patients that developed a major acute cardiovascular event, stroke, or device dislocation/embolization. There was a single case of major bleeding (3.2%) and 3 cases of acute kidney injury (9.7%). At 3 months, no patients experienced a stroke, one patient had a device-related thrombus (3.4%), one patient showed a significant peri-device leak, and one patient had a persistent iatrogenic atrial septal defect.
Conclusions: Our study shows that percutaneous LAAO may represent a feasible alternative strategy for stroke prevention, that can be safely performed in high-risk, multimorbid patients with high bleeding risk or contraindications to oral anticoagulation.
Müller, Angelina ; Gruhn, Sebastian ; Sawicki, Olga Anastasia ; Glushan, Anastasiya ; Witte, Claudia ; Klaaßen-Mielke, Renate ; Lembeck, Burkhard ; Gerlach, Ferdinand M. ; Greiner, Wolfgang ; Karimova, Kateryna
Objective: To evaluate a novel healthcare programme for the treatment of patients with hip and knee osteoarthritis in southern Germany in terms of clinical and health economic outcomes. The study is based on claims data from 2014 to 2017.
Methods: We conducted a retrospective comparative cohort study of 9768 patients with hip and knee osteoarthritis, of whom 9231 were enrolled in a collaborative ambulatory orthopaedic care programme (intervention group), and 537 patients received usual orthopaedic care (control group). Key features of the programme are coordinated care, morbidity-adapted reimbursement and extended consultation times. Multivariable analysis was performed to determine effects on health utilisation outcomes. The economic analysis considered annual costs per patient from a healthcare payer perspective, stratified by healthcare service sector. Besides multivariable regression analyses, bootstrapping was used to estimate confidence intervals for predicted mean costs by group.
Results: Musculoskeletal-disease-related hospitalisation was much less likely among intervention group patients than control group patients [odds ratio (OR): 0.079; 95% CI: 0.062–0.099]. The number of physiotherapy prescriptions per patient was significantly lower in the intervention group (RR: 0.814; 95% CI: 0.721–0.919), while the likelihood of participation in exercise programmes over one year was significantly higher (OR: 3.126; 95% CI: 1.604–6.094). Enrolment in the programme was associated with significantly higher ambulatory costs (€1048 vs. €925), but costs for inpatient care, including hospital stays, were significantly lower (€1003 vs. €1497 and €928 vs. €1300 respectively). Overall annual cost-savings were €195 per patient.
Conclusions: Collaborative ambulatory orthopaedic care was associated with reduced hospitalisation in patients with hip and knee osteoarthritis. Health costs for programme participants were lower overall, despite higher costs for ambulatory care.
Schweiger, Josef ; Erdelt, Kurt-Jürgen ; Graf, Tobias ; Sciuk, Thomas ; Edelhoff, Daniel ; Güth, Jan-Frederik
The thickness of a material has a significant impact on its fracture load. The aim of the study was to find and describe a mathematical relationship between the material thickness and the fracture load for dental all-ceramics. In total, 180 specimens were prepared from a leucite silicate ceramic (ESS), a lithium disilicate ceramic (EMX), and a 3Y-TZP zirconia ceramic (LP) in five thicknesses (0.4, 0.7, 1.0, 1.3, and 1.6 mm; n = 12). The fracture load of all specimens was determined using the biaxial bending test according to the DIN EN ISO 6872. The regression analyses for the linear, quadratic, and cubic curve characteristics of the materials were conducted, and the cubic regression curves showed the best correlation (coefficients of determination (R2): ESS R2 = 0.974, EMX R2 = 0.947, LP R2 = 0.969) for the fracture load values as a function of the material thickness. A cubic relationship could be described for the materials investigated. Applying the cubic function and material-specific fracture-load coefficients, the respective fracture load values can be calculated for the individual material thicknesses. These results help to improve and objectify the estimation of the fracture loads of restorations, to enable a more patient- and indication-centered situation-dependent material choice.
Ziel dieser Studie war es, zu untersuchen, ob der Ausbildungsstand des Operierenden einen Einfluss auf das Ergebnis der Ileostomarückverlagerung (ILSRV) bei den Patienten hat. Die ILSRV ist eine der ersten Operationen am Darm, die Assistenzärztinnen und Assistenzärzte durchführen. Dennoch können bei dieser Operation potenziell lebensbedrohliche Komplikationen, wie die Undichtigkeit der Naht (Anastomoseninsuffizienz), auftreten. Um eine ausreichende Patientensicherheit zu gewährleisten, sollte daher sichergestellt werden, dass die Durchführung dieser Operation durch Assistenzärztinnen und Assistenzärzte keine erhöhte postoperative Morbidität und Letalität für Patienten verursacht.
Für diese Studie wurden 300 Patienten mit einer Ileostomarückverlegung retrospektiv untersucht. Als primärer Endpunkt wurde die Morbidität, entsprechend der Clavien-Dindo-Klassifikation (CDC), mit besonderem Augenmerk auf den Ausbildungsstand der Operierenden definiert. Als sekundärer Endpunkt wurde die postoperative Darmmotilitätss