A gap analysis of the potential use of resuscitative endovascular balloon occlusion of the aorta (REBOA) in trauma at two major Canadian trauma centers.

OBJECTIVE: Uncontrolled hemorrhage poses significant morbidity and mortality among injured patients. Resuscitative endovascular balloon occlusion of the aorta (REBOA) utilizes a rapidly-administered minimally invasive transfemoral balloon catheter that is inflated for aortic occlusion, allowing for time to arrange definitive surgical or angiographic intervention. As indications for its use continue to evolve, this study sought to evaluate whether there is a potential need for REBOA implementation in two high-volume trauma centers in Edmonton. METHODS: Patient data within our provincial trauma registry was reviewed between 2015 and 2017 to identify major trauma patients (Injury Severity Score ≥ 12). Patients eligible for REBOA included patients with blunt or penetrating trauma to the torso or pelvis, AND death prior to discharge; and patients taken to the operating room or interventional radiology suite within 4 h of arrival. Charts were reviewed to determine if patients met current conventional criteria for REBOA. RESULTS: Out of 3415 trauma patients during our study period, 237 patients met the registry screen as potentially eligible for REBOA. After primary researcher review, 67 patients underwent full chart review and then 2 trauma surgeons determined that 38 (1.1% of the study population) met criteria for deploying REBOA. CONCLUSION: A small but significant number of trauma patients at the two trauma centers were identified as potential candidates for REBOA use. Implementation of a REBOA program should be done in alignment with existing clinical practice guidelines and professional society recommendations.

RéSUMé: OBJECTIF: L'hémorragie incontrôlée entraîne une morbidité et une mortalité importantes chez les patients blessés. Le clampage aortique par sonde d'occlusion aortique endovasculaire (resuscitative endovascular balloon occlusion of the aorta [REBOA]) utilise un cathéter à ballonnet transfémoral mini-invasif à administration rapide qui est gonflé pour l'occlusion aortique, ce qui laisse le temps d'organiser une intervention chirurgicale ou angiographique définitive. Alors que les indications de son utilisation continuent d'évoluer, cette étude a cherché à évaluer s'il y avait un besoin potentiel de mise en œuvre de REBOA dans deux centres de traumatologie à haut volume à Edmonton. MéTHODES: Les données sur les patients dans notre registre provincial des traumatismes ont été examinées entre 2015 et 2017 afin d'identifier les patients traumatisés majeurs (Score de gravité des blessures ≥ 12). Les patients éligibles au REBOA comprenaient des patients présentant un traumatisme contondant ou pénétrant au torse ou au bassin, ET le décès avant la sortie; et les patients conduits à la salle d'opération ou à la salle de radiologie interventionnelle dans les 4 heures suivant leur arrivée. Les graphiques ont été examinés pour déterminer si les patients répondaient aux critères conventionnels actuels de REBOA. RéSULTATS: Sur les 3 415 patients traumatisés pendant notre période d'étude, 237 patients ont répondu à l'examen du registre comme étant potentiellement éligibles pour le REBOA. Après examen par le chercheur principal, soixante-sept patients ont été soumis à un examen complet de leur dossier, puis deux chirurgiens traumatologues ont déterminé que 38 (1,1 % de la population étudiée) répondaient aux critères de déploiement de la REBOA. CONCLUSION: Un nombre restreint mais significatif de patients traumatisés dans les deux centres de traumatologie a été identifié comme des candidats potentiels à l'utilisation de REBOA. La mise en œuvre d'un programme REBOA doit se faire en conformité avec les directives de pratique clinique existantes et les recommandations de la société professionnelle.

A practical approach in bioreactor scale-up and process transfer using a combination of constant P/V and vvm as the criterion.

Bioreactor scale-up is a critical step in the production of therapeutic proteins such as monoclonal antibodies (MAbs). With the scale-up criterion such as similar power input per volume or O2 volumetric mass transfer coefficient ( kLa), adequate oxygen supply and cell growth can be largely achieved. However, CO2 stripping in the growth phase is often inadequate. This could cascade down to increased base addition and osmolality, as well as residual lactate increase and compromised production and product quality. Here we describe a practical approach in bioreactor scale-up and process transfer, where bioreactor information may be limited. We evaluated the sparger kLa and kLaCO2 (CO2 volumetric mass transfer coefficient) from a range of bioreactor scales (3-2,000 L) with different spargers. Results demonstrated that kLa for oxygen is not an issue when scaling from small-scale to large-scale bioreactors at the same gas flow rate per reactor volume (vvm). Results also showed that sparging CO2 stripping, kLaCO2, is dominated by the gas throughput. As a result, a combination of a minimum constant vvm air or N2 flow with a similar specific power was used as the general scale-up criterion. An equation was developed to determine the minimum vvm required for removing CO2 produced from cell respiration. We demonstrated the effectiveness of using such scale-up criterion with five MAb projects exhibiting different cell growth and metabolic characteristics, scaled from 3 to 2,000 L bioreactors across four sites. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1146-1159, 2017.

Scale-up of Agrobacterium-mediated transient protein expression in bioreactor-grown Nicotiana glutinosa plant cell suspension culture.

The reporter gene beta-glucuronidase was transiently expressed in a 51-L bioreactor-grown plant cell suspension culture of Nicotiana glutinosa at a yield of approximately 1.1 mg through co-culture with an auxotrophic strain of Agrobacterium tumefaciens. The three order of magnitude scale-up involved the investigation of factors contributing to transient expression including the timing of Agrobacterium inoculation relative to the plant cell growth phase, plant tissue culture hormonal triggers and plant cell cycle synchronization. The co-culture process was simplified to facilitate implementation in a pilot-scale bioreactor. At the shake flask scale it was determined that elevated concentrations of oxygen in the headspace were detrimental to transient expression levels and the addition of acetosyringone to the co-culture had a negligible effect. The bacterial preparation process was also streamlined, permitting the direct transfer of the Agrobacterium culture from a bench-scale fermentor to the pilot-scale plant cell culture bioreactor. Increasing expression levels and overcoming batch-to-batch variability despite extensive procedure systemization remain the major technical hurdles.