Supplementary Oxygenation Research Articles

Abstract 4230: Patient-derived tumoroid platforms with progressing tumor microenvironment representability reveals efficacy and resistance patterns in pre-clinical HSP90i regimen testing for improved clinical insights

Abstract Introduction: Drug candidates advance to phase I clinical trial after rigorous optimization at preclinical stage and yet nine out of ten drug candidates fail during clinical trials and approval stage. Lack of clinical efficacy is a major contributor (~ 50%) towards this 90% of the failure at clinical trials. Tremendous efforts are being taken to demonstrate drug efficacy in preclinical studies by mitigating the biological discrepancy of molecular target between human disease and the model used for the validation. Herein this study, we aim to showcase therapeutic responses of heat-shock protein 90 (HSP90) inhibitor regimens (HSP90i only and HSP90i + Doxorubicin combination) against three-dimensional (3D), patient-derived tumoroid (PDT) model platforms with progressing tumor microenvironment (TME) representability by incorporating supplementary TME structure, immunity, and oxygenation. Revelations on efficacy and resistance patterns of such drug treatments on increasingly complex models is aimed at providing unique insights to tumor and drug-drug interplay. Methods: Human Uterine Adenosarcoma PDT models were prepared across three COMPASS (Custom Organoid Modeling Platform for Accurate SolutionS) platforms: 1) COMPASS 1a - Non-scaffold 2) COMPASS 3b - Scaffold + Immune cells and 3) COMPASS 3d - Scaffold + Immune cells + Oxygenation. The various platforms were tested against two regimens A) HSP90i only [50 nM and 100 nM] and B) HSP90i [50 nM and 100 nM] + Doxorubicin [50 nM]. Tumor size and volume assessment were carried out on Days 3 and 7 post-treatment -with statistical done via one-way ANOVA, followed by student’s t test for significance (p<0.05, n=3). Results: While a simpler platform COMPASS 1a showcased the therapeutic efficacy of monotherapeutic HSP90i [at 100 nM] (p<0.05), progressively complex models (COMPASS 3b and COMPASS 3d) have otherwise indicated the lack of significant tumor volume changes. On the other hand, current findings on combination therapies of HSP90i and Doxorubicin have revealed persistent therapeutic resistance (even suggestive of patterns of increasing tumor growth) on COMPASS 1a, necessitating further comparisons on the more complex models. Conclusion: Our results demonstrate the need to test drugs in context of TME and oxygenation to help stratify patients to develop better clinical trials based on patient tumor characteristics of vascularization and immunogenicity. We plan to test several different drug modalities and cancer types for these parameters to demonstrate the need and effectiveness of testing prior to taking the drugs to the clinic. Citation Format: Huckie Del Mundo, Damieanus O. Ochola, Bhuvanesh Dave, Preethi Samuel. Patient-derived tumoroid platforms with progressing tumor microenvironment representability reveals efficacy and resistance patterns in pre-clinical HSP90i regimen testing for improved clinical insights [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4230.

Effects of wearing a mask on oxygenation of subjects with spontaneous breathing during supplementary oxygen through facemask

During the COVID-19 epidemic, our national guidelines have suggested that surgical patients should wear a mask to decrease the potential transmission of COVID-19 in the operating room, as long as the condition allows. However, so far, there is no study to discuss the influence of wearing a mask on the ventilation and blood oxygenation status in patients of spontaneous breathing with supplementary oxygen through an anesthetic facemask. This is a before-after study in the same patient, and 10 healthy volunteers were recruited, by testing the arterial blood gas parameters at key time points before and after oxygen inhalation to evaluate the effects of two different supplementary oxygen methods ('disposable medical mask + anesthetic facemask' and 'anesthetic facemask only') on the oxygenation of subjects. Our data demonstrated whether wearing a disposable medical mask or not could effectively increase the oxygen supply of the subjects compared with the basic value before oxygen inhalation; however, compared with the group without mask, the arterial oxygen partial (PaO 2) reduced significantly at each time points when subjects wearing a disposable medical mask. There was no significant difference in other parameters, and our data showed that age growth and smoking had no significant effects on the difference of PaO 2 between the groups with and without masks. This study demonstrates effective oxygen supplementation through anesthetic facemask in subjects with spontaneous breathing who is wearing a disposable medical mask, whose pulse oxygen saturation and arterial oxygen saturation can reach 100% rapidly, and this provides a theoretical basis for the management of patients with disseminated respiratory diseases to wear masks in the operating room; however, the rate and amount of PaO 2 increase are both decreased as compared to those who is not wearing a disposable medical mask during supplementary oxygenation. Whether this difference will affect the clinical outcome needs further study.

Supplemental oxygen therapy in COVID-19

South Africa face a significant shortage of ventilator-supported intensive care (ICU) beds during the peak phase of the COVID-19 pandemic, further exacerbated by severe ICU-staff shortages. It is also recognised that the mortality rate for ventilated patients might be as high as 88%. In the absence of a vaccine and proven effective pharmacotherapy, it is important to understand the pathophysiological processes causing progression. Early type-L COVID-19, associated with pulmonary thrombo-embolism, may be amenable to treatment with careful anti-coagulation and supplementary oxygenation strategies. This could attenuate the severe hyperventilation phase causing patient self-inflicted lung injury (P-SILI) that contributes to the development of type-H COVID-19 pneumonia. Type-H is an ARDS variant requiring intubation and ventilation and is associated with a very high mortality rate. Stepwise non-invasive positive pressure ventilation strategies (NIPPV) providing supplementary oxygen have shown benefit and, in the South African context, may be the only realistic strategy to deal with high numbers of patients during the early type-L phase of the disease. To address this, a mobile wall unit has been created that allows for stepwise supplementary oxygen therapy according to protocol – including NIPPV as well as standard ventilation. The unit can support modified wards, field hospitals or high care areas in existing facilities. It allows for NIPPV support within a hood system linked to scavenger lines addressing aerolisation. Standard humidification, flow regulators, vacuum systems, HFNC and CPAP systems, as well as monitoring equipment that are readily available in South Africa, can be linked to the system addressing availability issues.

Critical Care Air Transport Team Evacuation of Medical Patients Without Traumatic Injury.

Air Force Critical Care Air Transport Teams (CCATTs) provide fixed-wing aeromedical evacuation for combat casualties. Multiple studies have evaluated CCATT trauma patients; however, nearly 50% of patients medically evacuated from combat theaters are for nontraumatic medical illnesses to include stroke, myocardial infarctions, overdose, and pulmonary emboli. Published data are limited regarding illness types, in-flight procedures, and adverse events. The objective of our study was to characterize patients with nontraumatic medical illnesses transferred via CCATT to include a description of in-flight procedures and events. We performed a retrospective review of CCATT medical records of patients with nontraumatic medical illnesses transported via CCATT from theater of operations to Landstuhl Regional Medical Center between January 2007 and April 2015. We abstracted data from CCATT records to include demographics, description of current illness, vital signs, labs, in-flight procedures and medications, and in-flight adverse events. Following descriptive analysis, comparative tests were performed based on service status of patients and primary diagnoses. We reviewed 672 records of critically ill medical patients transported via CCATT, most of whom were male (90%, n = 606). Approximately 56% of the patients were U.S. active duty members; the remainder included U.S. contractors and civilians, and foreign citizens or unknown. The three categories (active duty, contractor/civilian, foreign/unknown) significantly differed from one another in age. Over half of the patients received a primary or secondary cardiac diagnosis. The most common in-flight procedures and medications included supplementary oxygenation, anticoagulant/antiplatelet medications, analgesics, and ventilation. Up to 20% of patients required continuous medication infusions other than analgesics. Patients most frequently experienced in-flight complications related to their primary diagnoses. Fifty-six percent (672) of 1,209 CCATT records that were queried were of patients with medical conditions. The most common primary diagnoses of CCATT medical patients were cardiac, pulmonary, and neurological in etiology. Mechanical ventilation and continuous medication infusions were required in approximately 20% of patients. The data provided by this study may assist in guiding future CCATT training requirements and resource allocation, as well as clinical practice guideline development.

Use of Bicaval Dual-Lumen Catheter for Adult Venovenous Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) provides supplementary oxygenation and carbon dioxide removal for selected patients on mechanical ventilatory support. Venovenous ECMO is traditionally established by dual cannulation of the internal jugular and femoral veins. We report our institutional experience using single-site, dual-lumen cannula for venovenous ECMO as an alternative to the 2-catheter approach. This approach minimizes recirculation and avoids use of the femoral site, which confers potential advantages. This is a retrospective review of a single institution's experience with a new bicaval dual lumen ECMO cannula. During a 19-month period, 27 consecutive patients were placed on ECMO using this catheter inserted through the right internal jugular vein. Single-site venovenous ECMO support was uneventfully initiated in 26 of the 27 patients (median age, 42 years; interquartile range, 31 to 58 years) and achieved full flows and adequate gas exchange. Median ventilator days before ECMO was 1 day (interquartile range, 0.25 to 3.5 days). The median duration of ECMO support was 9 days (interquartile range, 5.5 to 11.5 days). Decannulation was achieved in 70% of the patients and extubation in 59%. Two were bridged to lung transplantation and are still alive. The overall survival and hospital discharge rate was 56%. There was no device failure or in-cannula thrombosis. One superior vena cava injury occurred, and one cannula required repositioning. Single-site venovenous ECMO has advantages compared with traditional venovenous ECMO. Using image guidance, the cannula can reliably be used in prolonged venovenous ECMO cases.

Increased oxygen administration during awake carotid surgery can reverse neurological deficit following carotid cross-clamping

We describe the management of two patients undergoing awake carotid surgery who developed signs of cerebral ischaemia following cross-clamping of the internal carotid artery. Administration of oxygen 100% with a close-fitting anaesthetic facemask reversed the neurological deficit, avoiding the need for insertion of an internal carotid artery shunt. Thus, the incidence of shunt insertion, which is reduced by the use of regional rather than general anaesthesia, could be reduced further by supplementary oxygenation. The possible mechanism and implications are discussed.

Oxygenator support for partial left-heart bypass

Partial left-heart bypass provides circulatory support and distal perfusion for repair of thoracic and thoracoabdominal aortic disease without requiring full anticoagulation. Unfortunately some patients, such as those with significant lung contusion in the setting of trauma or those with severe chronic obstructive pulmonary disease and degenerative aneurysms, do not tolerate single-lung ventilation. We have recently modified our left-heart bypass circuit in selected cases to provide supplementary oxygenation, making this technique more broadly applicable.

Stocking density, growth and growth variation in juvenile turbot, Scophthalmus maximus (Rafinesque)

Although high stocking densities of turbot have been achieved in culture using supplementary oxygenation, this rearing strategy ignores the possibility that high densities may interfere with behavioural interactions between individuals and thereby affect biomass gain. This study describes the effect of stocking density on the growth of juvenile turbot populations. Groups of juvenile turbot were reared at four different densities (initial densities: 0.7, 1.1, 1.5 and 1.8 kg/m 2) for 45 days. Treatment density had a significant effect on turbot growth rates over the experimental period. Fish held at the highest density showed lower growth rates and mean weights at the conclusion of the study than fish held at lower densities. The dispersion in fish weights was also affected by stocking density. The variation in fish weights was greatest in the highest density group and as stocking densities increased the growth of some individuals was suppressed. It is concluded that growth of juvenile turbot can be significantly increased and more homogeneous weights achieved by stocking the fish at lower densities than previously reported.

Corneal oxygenation: blink frequency as a variable in rigid contact lens wear.

Using a micropolarographic system, we measured the responses of six human corneas to nine oxygen exposure conditions: to air (continuous open-eye) with no contact lens in place, and to eight interblink intervals (1, 2, 3, 4, 5, 6, 7, and 300 s durations) with an oxygen impermeable lens in place. The corneal oxygen uptake rates immediately following each of those conditions were direct indices of tear bulk-flow exchange under a rigid contact lens as an oxygen route. Greatest efficiencies in reducing corneal oxygen demand were associated with the two highest blink frequencies examined (namely, for interblink intervals of 2 s or less). Even at those frequencies oxygen demands ranging from 4 to 6 times the open-eye, non-wearing, baseline rate for each eye typically occurred, clearly justifying the need for a supplementary oxygenation route, for example, directly through rigid contact lens materials having inherently high oxygen permeabilities.