Use of the GlideScope®-Ranger for pre-hospital intubations by anaesthesia trained emergency physicians – an observational study

Background: Pre-hospital endotracheal intubation is more difficult than in the operating room (OR). Therefore, enhanced airway management devices such as video laryngoscopes may be helpful to improve the success rate of pre-hospital intubation. We describe the use of the Glidescope®-Ranger (GS-R) as an alternative airway tool used at the discretion of the emergency physician (EP) in charge. Methods: During a 3.5 year period, the GS-R was available to be used either as the primary or backup tool for pre-hospital intubation by anaesthesia trained EP with limited expertise using angulated videolaryngoscopes. Results: During this period 672 patients needed pre-hospital intubation of which the GS-R was used in 56 cases. The overall GS-R success rate was 66 % (range of 34–100 % among EP). The reasons for difficulties or failure included inexperience of the EP with the GS-R, impaired view due to secretion, vomitus, blood or the inability to see the screen in very bright environment due to sunlight. Conclusion: Special expertise and substantial training is needed to successfully accomplish tracheal intubation with the GS-R in the pre-hospital setting. Providers inexperienced with DL as well as video-assisted intubation should not expect to be able to perform tracheal intubation easily just because a videolaryngoscope is available. Additionally, indirect laryngoscopy might be difficult or even impossible to achieve in the pre-hospital setting due to impeding circumstances such as blood, secretions or bright sun-light. Therefore, videolaryngoscopes, here the GS-R, should not be considered as the “Holy Grail” of endotracheal intubation, neither for the experts nor for inexperienced providers. Electronic supplementary material The online version of this article (doi:10.1186/s12873-016-0069-2) contains supplementary material, which is available to authorized users

Electrospun PLLA Nanofiber Scaffolds and Their Use in Combination with BMP-2 for Reconstruction of Bone Defects

Introduction Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). Materials and Methods The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). Results PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. Conclusion Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus

Genetic screens identify a context-specific PI3K/p27Kip1 node driving extrahepatic biliary cancer

Biliary tract cancer ranks among the most lethal human malignancies, representing an unmet clinical need. Its abysmal prognosis is tied to an increasing incidence and a fundamental lack of mechanistic knowledge regarding the molecular basis of the disease. Here, we show that the Pdx1-positive extrahepatic biliary epithelium is highly susceptible toward transformation by activated PIK3CAH1047R but refractory to oncogenic KrasG12D. Using genome-wide transposon screens and genetic loss-of-function experiments, we discover context-dependent genetic interactions that drive extrahepatic cholangiocarcinoma (ECC) and show that PI3K signaling output strength and repression of the tumor suppressor p27Kip1 are critical context-specific determinants of tumor formation. This contrasts with the pancreas, where oncogenic Kras in concert with p53 loss is a key cancer driver. Notably, inactivation of p27Kip1 permits KrasG12D-driven ECC development. These studies provide a mechanistic link between PI3K signaling, tissue-specific tumor suppressor barriers, and ECC pathogenesis, and present a novel genetic model of autochthonous ECC and genes driving this highly lethal tumor subtype

High class filtering facepiece (FFP) are fundamental and effective in protection of emergency health care workers: an observational cohort study in a German community

Background!#!Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious airborne virus inducing pandemic coronavirus disease 2019 (COVID-19). This is most relevant for medical staff working under harmful conditions in emergencies often dealing with patients and an undefined SARS-CoV-2 status. We aimed to measure the effect of high-class filtering facepieces (FFP) in emergency medical service (EMS) staff by analyzing seroprevalence and history of positive polymerase chain reaction (PCR) for SARS-CoV-2.!##!Method!#!This observational cohort study included workers in EMS, who were compared with hospital staff (HS) and staff, which was not directly involved in patient care (NPC). All direct patient contacts of EMS workers were protected by FFP2/N95 (filtering face piece protection class 2/non-oil-based particulates filter efficiency 95%) masks, whereas HS was protected by FFP2/N95 exclusively when a patient had a proven or suspected SARS-CoV-2 infection. NPC was not protected by higher FFP. The seroprevalence of SARS-CoV-2 antibodies was analyzed by immunoassay by end of 12/2020 together with the history of a positive PCR. In addition, a self-assessment was performed regarding the quantity of SARS-CoV-2 positive contacts, about flu symptoms and personal belief of previous COVID-19 infections.!##!Results!#!The period in which contact to SARS-CoV-2 positive patients has been possible was 10 months (March to December 2020)-with 54,681 patient contacts documented for EMS-either emergencies (n = 33,241) or transportation services (n = 21,440). Seven hundred-thirty (n = 730) participants were included into the study (n = EMS: 325, HS: 322 and NPC: 83). The analysis of the survey showed that the exposure to patients with an unknown and consecutive positive SARS-CoV-2 result was significantly higher for EMS when compared to HS (EMS 55% vs. HS 30%, p = 0.01). The incidence of a SARS-CoV-2 infection in our cohort was 1.2% (EMS), 2.2% (HS) and 2.4% (NPC) within the three groups (ns) and lowest in EMS. Furthermore, the belief of previous COVID-19 was significant higher in EMS (19% vs. 10%), CONCLUSION: The consistent use of FFP2/N95 in EMS is able to prevent work-related SARS-CoV-2 infections in emergency situations. The significance of physical airway protection in exposed medical staff is still relevant especially under the aspect of new viral variants and unclear effectiveness of new vaccines

Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers

X-ray crystallography at X-ray free-electron laser sources is a powerful method for studying macromolecules at biologically relevant temperatures. Moreover, when combined with complementary techniques like X-ray emission spectroscopy, both global structures and chemical properties of metalloenzymes can be obtained concurrently, providing insights into the interplay between the protein structure and dynamics and the chemistry at an active site. The implementation of such a multimodal approach can be compromised by conflicting requirements to optimize each individual method. In particular, the method used for sample delivery greatly affects the data quality. We present here a robust way of delivering controlled sample amounts on demand using acoustic droplet ejection coupled with a conveyor belt drive that is optimized for crystallography and spectroscopy measurements of photochemical and chemical reactions over a wide range of time scales. Studies with photosystem II, the phytochrome photoreceptor, and ribonucleotide reductase R2 illustrate the power and versatility of this method