Value of arterial blood gas analysis in patients with acute dyspnea: an observational study

ABSTRACT: INTRODUCTION: The diagnostic and prognostic value of arterial blood gas analysis (ABGA) parameters in unselected patients presenting with acute dyspnea to the Emergency Department (ED) is largely unknown. METHODS: We performed a post-hoc analysis of two different prospective studies to investigate the diagnostic and prognostic value of ABGA parameters in patients presenting to the ED with acute dyspnea. RESULTS: We enrolled 530 patients (median age 74 years). ABGA parameters were neither useful to distinguish between patients with pulmonary disorders and other causes of dyspnea nor to identify specific disorders responsible for dyspnea. Only in patients with hyperventilation from anxiety disorder, the diagnostic accuracy of pH and hypoxemia rendered valuable with an area under the receiver operating characteristics curve (AUC) of 0.86. Patients in the lowest pH tertile more often required admission to Intensive Care Unit (28% vs 12% in the first tertile, P >0.001) and had higher in-hospital (14% vs 5%, P =0.003) and 30-day mortality (17% vs 7%, P =0.002). Cumulative mortality rate was higher in the first (37%), than in the second (28%), and the third tertile (23%, P =0.005) during 12 months follow-up. pH at presentation was an independent predictor of 12-month mortality in multivariable Cox proportional hazard analysis both for patients with pulmonary (P =0.043) and non-pulmonary disorders (P =0.038). CONCLUSIONS: ABGA parameters provide limited diagnostic value in patients with acute dyspnea, but pH is an independent predictor of 12 months mortality

On the reproducibility of extrusion-based bioprinting: round robin study on standardization in the field

The outcome of three-dimensional (3D) bioprinting heavily depends, amongst others, on the interaction between the developed bioink, the printing process, and the printing equipment. However, if this interplay is ensured, bioprinting promises unmatched possibilities in the health care area. To pave the way for comparing newly developed biomaterials, clinical studies, and medical applications (i.e. printed organs, patient-specific tissues), there is a great need for standardization of manufacturing methods in order to enable technology transfers. Despite the importance of such standardization, there is currently a tremendous lack of empirical data that examines the reproducibility and robustness of production in more than one location at a time. In this work, we present data derived from a round robin test for extrusion-based 3D printing performance comprising 12 different academic laboratories throughout Germany and analyze the respective prints using automated image analysis (IA) in three independent academic groups. The fabrication of objects from polymer solutions was standardized as much as currently possible to allow studying the comparability of results from different laboratories. This study has led to the conclusion that current standardization conditions still leave room for the intervention of operators due to missing automation of the equipment. This affects significantly the reproducibility and comparability of bioprinting experiments in multiple laboratories. Nevertheless, automated IA proved to be a suitable methodology for quality assurance as three independently developed workflows achieved similar results. Moreover, the extracted data describing geometric features showed how the function of printers affects the quality of the printed object. A significant step toward standardization of the process was made as an infrastructure for distribution of material and methods, as well as for data transfer and storage was successfully established

On the reproducibility of extrusion-based bioprinting: round robin study on standardization in the field

The outcome of three-dimensional (3D) bioprinting heavily depends, amongst others, on the interaction between the developed bioink, the printing process, and the printing equipment. However, if this interplay is ensured, bioprinting promises unmatched possibilities in the health care area. To pave the way for comparing newly developed biomaterials, clinical studies, and medical applications (i.e. printed organs, patient-specific tissues), there is a great need for standardization of manufacturing methods in order to enable technology transfers. Despite the importance of such standardization, there is currently a tremendous lack of empirical data that examines the reproducibility and robustness of production in more than one location at a time. In this work, we present data derived from a round robin test for extrusion-based 3D printing performance comprising 12 different academic laboratories throughout Germany and analyze the respective prints using automated image analysis (IA) in three independent academic groups. The fabrication of objects from polymer solutions was standardized as much as currently possible to allow studying the comparability of results from different laboratories. This study has led to the conclusion that current standardization conditions still leave room for the intervention of operators due to missing automation of the equipment. This affects significantly the reproducibility and comparability of bioprinting experiments in multiple laboratories. Nevertheless, automated IA proved to be a suitable methodology for quality assurance as three independently developed workflows achieved similar results. Moreover, the extracted data describing geometric features showed how the function of printers affects the quality of the printed object. A significant step toward standardization of the process was made as an infrastructure for distribution of material and methods, as well as for data transfer and storage was successfully established

Value of arterial blood gas analysis in patients with acute dyspnea: an observational study

The diagnostic and prognostic value of arterial blood gas analysis (ABGA) parameters in unselected patients presenting with acute dyspnea to the Emergency Department (ED) is largely unknown. We performed a post-hoc analysis of two different prospective studies to investigate the diagnostic and prognostic value of ABGA parameters in patients presenting to the ED with acute dyspnea. We enrolled 530 patients (median age 74 years). ABGA parameters were neither useful to distinguish between patients with pulmonary disorders and other causes of dyspnea nor to identify specific disorders responsible for dyspnea. Only in patients with hyperventilation from anxiety disorder, the diagnostic accuracy of pH and hypoxemia rendered valuable with an area under the receiver operating characteristics curve (AUC) of 0.86. Patients in the lowest pH tertile more often required admission to intensive care unit (28% vs 12% in the first tertile, P < 0.001) and had higher in-hospital (14% vs 5%, P = 0.003) and 30-day mortality (17% vs 7%, P = 0.002). Cumulative mortality rate was higher in the first (37%), than in the second (28%), and the third tertile (23%, P = 0.005) during 12 months follow-up. pH at presentation was an independent predictor of 12-month mortality in multivariable Cox proportional hazard analysis both for patients with pulmonary (P = 0.043) and non-pulmonary disorders (P = 0.038). ABGA parameters provide limited diagnostic value in patients with acute dyspnea, but pH is an independent predictor of 12 months mortality

An In Vitro Model Using TRIS-Buffered Plasma-Activated Water to Reduce Pathogenic Microorganisms Involved in Digital Dermatitis Infection in Cattle

Bovine digital dermatitis is an important infectious claw disease caused by multimicrobial infections with bacteria such as Fusobacterium (F.) necrophorum or Porphyromonas (P.) levii. To analyze the antibacterial effects of a TRIS-buffered plasma-activated water (Tb-PAW) on the bacterial number of F. necrophorum, P. levii, Escherichia (E.) coli, Staphylococcus (S.) aureus and Clostridium (C.) sporogenes 1 mL of each bacterial solution (106–108 CFU/mL) was incubated with 9 mL Tb-PAW up to 15 min. E. coli, F. necrophorum and P. levii were significantly reduced by 5.0 log after 1 min of treatment, while S. aureus and C. sporogenes required 15 min to reach a 3.0 log reduction. The addition of bovine serum albumin did not negatively affect the bactericidal effect. Tb-PAW storage at 7 °C and 21 °C is possible for up to 24 h without any change in the bactericidal effect, while Tb-PAW stored at 30 °C can only be used for a period of 12 h. The present data indicate that Tb-PAW can be used to reduce various bacteria even under the influence of different parameters. However, due to the complexity of Tb-PAW, further studies are required to ensure its microbicidal activity before practical application

An In Vitro Model Using TRIS-Buffered Plasma-Activated Water to Reduce Pathogenic Microorganisms Involved in Digital Dermatitis Infection in Cattle

Bovine digital dermatitis is an important infectious claw disease caused by multimicrobial infections with bacteria such as Fusobacterium (F.) necrophorum or Porphyromonas (P.) levii. To analyze the antibacterial effects of a TRIS-buffered plasma-activated water (Tb-PAW) on the bacterial number of F. necrophorum, P. levii, Escherichia (E.) coli, Staphylococcus (S.) aureus and Clostridium (C.) sporogenes 1 mL of each bacterial solution (106&ndash;108 CFU/mL) was incubated with 9 mL Tb-PAW up to 15 min. E. coli, F. necrophorum and P. levii were significantly reduced by 5.0 log after 1 min of treatment, while S. aureus and C. sporogenes required 15 min to reach a 3.0 log reduction. The addition of bovine serum albumin did not negatively affect the bactericidal effect. Tb-PAW storage at 7 &deg;C and 21 &deg;C is possible for up to 24 h without any change in the bactericidal effect, while Tb-PAW stored at 30 &deg;C can only be used for a period of 12 h. The present data indicate that Tb-PAW can be used to reduce various bacteria even under the influence of different parameters. However, due to the complexity of Tb-PAW, further studies are required to ensure its microbicidal activity before practical application

Design and Functional Characterization of HIV-1 Envelope Protein-Coupled T Helper Liposomes

Functionalization of experimental HIV-1 virus-like particle vaccines with heterologous T helper epitopes (T helper VLPs) can modulate the humoral immune response via intrastructural help (ISH). Current advances in the conjugation of native-like HIV-1 envelope trimers (Env) onto liposomes and encapsulation of peptide epitopes into these nanoparticles renders this GMP-scalable liposomal platform a feasible alternative to VLP-based vaccines. In this study, we designed and analyzed customizable Env-conjugated T helper liposomes. First, we passively encapsulated T helper peptides into a well-characterized liposome formulation displaying a dense array of Env trimers on the surface. We confirmed the closed pre-fusion state of the coupled Env trimers by immunogold staining with conformation-specific antibodies. These peptide-loaded Env-liposome conjugates efficiently activated Env-specific B cells, which further induced proliferation of CD4+ T cells by presentation of liposome-derived peptides on MHC-II molecules. The peptide encapsulation process was then quantitatively improved by an electrostatically driven approach using an overall anionic lipid formulation. We demonstrated that peptides delivered by liposomes were presented by DCs in secondary lymphoid organs after intramuscular immunization of mice. UFO (uncleaved prefusion optimized) Env trimers were covalently coupled to peptide-loaded anionic liposomes by His-tag/NTA(Ni) interactions and EDC/Sulfo-NHS crosslinking. EM imaging revealed a moderately dense array of well-folded Env trimers on the liposomal surface. The conformation was verified by liposomal surface FACS. Furthermore, anionic Env-coupled T helper liposomes effectively induced Env-specific B cell activation and proliferation in a comparable range to T helper VLPs. Taken together, we demonstrated that T helper VLPs can be substituted with customizable and GMP-scalable liposomal nanoparticles as a perspective for future preclinical and clinical HIV vaccine applications. The functional nanoparticle characterization assays shown in this study can be applied to other systems of synthetic nanoparticles delivering antigens derived from various pathogens