Immobilisation nach elektrothermischem Shrinkage kollagenhaltigen Gewebes:histologische Auswertung einer in-vivo Tierversuchsstudie

In dieser Studie wurden die Ligg. patellae von Kaninchen mittels Radiofrequenz (RF)-Energie verkürzt und postoperativ immobilisiert. Ziel war es, die Auswirkungen einer postoperativen Immobilisation histologisch zu untersuchen. Die Evaluation der Sehnenheilung erfolgte überwiegend durch Polarisationsmikroskopie, Immunhistologie und TUNEL-Labeling. Mittels Bildanalyse, sowie histologischer Scores wurden die Effekte von RF-Behandlung auf Zellularität und Apoptose, extrazelluläre Matrix, Nervengewebe und Vaskularisierung untersucht. RF-Behandlung induziert Apoptose von Fibroblasten. Immobilisation reduziert während der frühen Phase der Heilung die Zellularität des Gewebes. Im histologischen Vergleich zeigen die immobilisierten Sehnen bessere Ergebnisse gegenüber den mobilen Sehnen. Von einer konsekutiv reduzierten Degradation und Neusynthese der Matrix profitiert die Gewebereifung und damit auch die biomechanische Stabilität der Sehnen. Wir empfehlen nach RF eine Immobilisation für 3-6 Wochen

Nanomechanics of the endothelial glycocalyx in experimental sepsis

The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, P<0.0001) and stiffness (0.34 ± 0.03 vs. 0.21 ± 0.01 pN/mn, P<0.0001) in septic mice (1 mg E. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to controls. Corresponding in vitro experiments revealed that sepsis-associated mediators, such as thrombin, LPS or Tumor Necrosis Factor-α alone were sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (-20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel approach to uncover mechanisms involved in deterioration and refurbishment of the eGC in sepsis

Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia

Background: Excessive tryptophan metabolism to kynurenine by the rate-limiting enzyme endothelial indoleamine 2,3-dioxygenase 1 (IDO) controls arterial vessel relaxation and causes hypotension in murine endotoxemia. However, its relevance in human endotoxemia has not been investigated so far. We thus aimed to study changes in blood pressure in parallel with tryptophan and kynurenine levels during experimental endotoxemia in humans. Findings: Six healthy male volunteers were given E. coli lipopolysaccharide (LPS; 4 ng/kg) as a 1-min intravenous infusion. They had levels of soluble E-Selectin and soluble vascular cell adhesion molecule-1 as well as IDO activity assessed as the kynurenine-to-tryptophan plasma ratio by liquid chromatography-tandem mass spectrometry at various time points during a 24 h time course. During endotoxemia, IDO activity significantly increased, reaching peak levels at 8 h after LPS infusion (44.0 ± 15.2 vs. 29.4 ± 6.8 at baseline, P<0.0001). IDO activity correlated inversely with the development of hypotension as shown by random effects linear regression models. Finally, IDO activity exhibited a kinetic profile similar to that of soluble endothelial-specific adhesion molecules. Conclusions: LPS is a triggering factor for the induction of IDO in men. Our findings strongly support the concept that the induction of IDO in the vascular endothelium contributes to hypotension in human sepsis

PD-L1 Dependent Immunogenic Landscape in Hot Lung Adenocarcinomas Identified by Transcriptome Analysis

Background: Lung cancer is the most frequent cause of cancer-related deaths worldwide. The clinical development of immune checkpoint blockade has dramatically changed the treatment paradigm for patients with lung cancer. Yet, an improved understanding of PD-1/PD-L1 checkpoint blockade- responsive biology is warranted. Methods: We aimed to identify the landscape of immune cell infiltration in primary lung adenocarcinoma (LUAD) in the context of tumoral PD-L1 expression and the extent of immune infiltration (&quot;hot&quot; vs. &quot;cold&quot; phenotype). The study comprises LUAD cases (n = 138) with &quot;hot&quot; (≥150 lymphocytes/HPF) and &quot;cold&quot; (&lt;150 lymphocytes/HPF) tumor immune phenotype and positive (&gt;50%) and negative (&lt;1%) tumor PD-L1 expression, respectively. Tumor samples were immunohistochemically analyzed for expression of PD-L1, CD4, and CD8, and further investigated by transcriptome analysis. Results: Gene set enrichment analysis defined complement, IL-JAK-STAT signaling, KRAS signaling, inflammatory response, TNF-alpha signaling, interferon-gamma response, interferon-alpha response, and allograft rejection as significantly upregulated pathways in the PD-L1-positive hot subgroup. Additionally, we demonstrated that STAT1 is upregulated in the PD-L1-positive hot subgroup and KIT in the PD-L1-negative hot subgroup. Conclusion: The presented study illustrates novel aspects of PD-L1 regulation, with potential biological relevance, as well as relevance for immunotherapy response stratification

Verfügbarkeit von Patienteninformationen in der Notaufnahme

Background!#!Fast access to information from other healthcare service providers is particularly important in emergency medicine, as the patients are often unknown and treatment decisions have to be made promptly.!##!Objectives!#!The study aims to identify the challenges that emergency departments face in obtaining information on patient history, the expected benefits of easier access to information and which information is most urgently needed.!##!Materials and methods!#!An online survey throughout Germany was carried out among medical staff working in emergency departments. In all, 181 questionnaires were fully completed and could be included in the data analysis.!##!Results!#!Of the respondents, 77.9% said it was difficult or very difficult to receive external data at the point of patient care. The survey participants estimate that they need an average of around 47 min to obtain information about one patient. 99.4% believe that patient care would benefit from an easier and faster information exchange. Medication lists, discharge letters, information on previous illnesses and allergies were classified as the most important data elements.!##!Conclusions!#!There is an urgent need for action with regard to the considerable effort involved in obtaining information on emergency patients. Digital solutions such as the recently introduced emergency data set can offer additional value for clinical emergency care if they are widely used

„C-Probleme“ des nichttraumatologischen Schockraummanagements

&lt;jats:title&gt;Zusammenfassung&lt;/jats:title&gt;&lt;jats:p&gt;Im Rahmen des nichttraumatologischen Schockraummanagements zur Versorgung kritisch kranker Patienten werden akute Störungen der Vitalfunktionen rasch detektiert und behandelt. Beim „primary survey“ (Erstversorgung) dient das etablierte ABCDE-Schema der strukturierten Untersuchung aller relevanten Vitalparameter. Akute Störungen werden hierbei unmittelbar detektiert und therapiert. „C-Probleme“ stellen den größten Anteil der ABCDE-Störungen bei nichttraumatologischen Schockraumpatienten dar und zeichnen sich durch eine hämodynamische Instabilität infolge hypovolämischer, obstruktiver, distributiver oder kardiogener Schockformen aus. Abhängig von den lokalen Versorgungsstrukturen umfasst die nichttraumatologische Schockraumversorgung hierbei auch die Stabilisierung von Patienten mit akutem Koronarsyndrom oder nach prähospitaler Reanimation (Cardiac Arrest Center).&lt;/jats:p&gt