Search

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus , we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combination with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low-resource locations., Competing Interests: MS Inventor on a relevant patentapplication held by Harvard University (PCT/US2021/012626), BC, HF, KP, ZI, TL, AK, SK, ML, SL, RM, SM, JM, MP, AS, KS, KS, DD, TP, JY, JP, DW, ZH, CH, JC, OP, JS, EW, MS No competing interests declared, EG Inventor on a relevant patentapplication held by Harvard University (PCT/US2021/012626). Hold equity in and is employed by Unravel Biosciences, Inc, TT Inventor on a relevant patent807 application held by Harvard University (PCT/US2021/012626), KA, EC, RL, IC, ZM, IJ, RV, LB Employee of Vascular Perfusion Solutions, ML Inventor on a relevant patent application held by Harvard University (PCT/US2021/012626). Hold equity in and is a member of the scientific advisory board of Unravel Biosciences, Inc, RN Inventor on a relevant patent application held by Harvard University (PCT/US2021/012626). Holds equity in, is a member of the board of directors, and is a current employee of Unravel Biosciences, Inc, DI Founder, board member and Scientific Advisory Board chair of, and holds equity in, Emulate Inc Inventors on a relevant patent application held by Harvard University (PCT/US2021/012626). Holds equity and is a member of the board of directors of Unravel Biosciences, Inc Member of the scientific advisory board of Vascular Perfusion Solutions

Background: Patients with rib fractures are at high risk for morbidity and mortality. This study prospectively examines bedside percent predicted forced vital capacity (% pFVC) in predicting complications for patients suffering multiple rib fractures. The authors hypothesize that increased % pFVC is associated with reduced pulmonary complications., Methods: Adult patients with =3 rib fractures admitted to a level I trauma center, without cervical spinal cord injury or severe traumatic brain injury, were consecutively enrolled. FVC was measured at admission and % pFVC values were calculated for each patient. Patient were grouped by % pFVC <30% (low), 30-49% (moderate), and =50% (high)., Results: A total of 79 patients were enrolled. Percent pFVC groups were similar except for pneumothorax being most frequent in the low group (47.8% vs. 13.9% and 20.0%, p = .028). Pulmonary complications were infrequent and did not differ between groups (8.7% vs. 5.6% vs. 0%, p = .198)., Discussion: Increased % pFVC was associated with reduced hospital and intensive care unit (ICU) length of stay (LOS) and increased time to discharge to home. Percent pFVC should be used in addition to other factors to risk stratify patients with multiple rib fractures. Bedside spirometry is a simple tool that can help guide management in resource-limited settings, especially in large-scale combat operations., Conclusion: This study prospectively demonstrates that % pFVC at admission represents an objective physiologic assessment that can be used to identify patients likely to require an increased level of hospital care., (2023.)

The authors describe an equipment list for an ultramobile, surgeon-carried equipment set that is specifically designed for missions that require the extremes of constraints on personnel and resources conducted outside the ring of golden hour access to damage control surgery (DCS) capabilities., (2021.)

Background: In military trauma, temporary vascular shunts restore arterial continuity until delayed vascular reconstruction, often for a period of hours. A novel US Air Force-developed trauma-specific vascular injury shunt (TS-VIS) incorporates an accessible side port for intervention or monitoring, which may improve patency under adverse hemodynamic conditions. Our objective was to evaluate TS-VIS patency in the setting of volume-limited resuscitation from hemorrhagic shock., Methods: Female swine (70-90 kg) underwent 30% hemorrhage and occlusion of the left external iliac artery for 30 minutes. Animals were allocated to one of three groups (n = 5 per group) by left external iliac artery treatment: Sundt shunt (SUNDT), TS-VIS with arterial pressure monitoring (TS-VIS), or TS-VIS with heparin infusion (10 μ/kg per hour, TS-VISHep). Animals were resuscitated with up to 3 U of whole blood to maintain a mean arterial pressure (MAP) of >60 mm Hg and were monitored for 6 hours. Bilateral femoral arterial flow was continuously monitored with transonic flow probes, and shunt thrombosis was defined as the absence of flow for greater than 5 minutes., Results: No intergroup differences in MAP or flow were observed at baseline or following hemorrhage. Animals were hypotensive at shunt placement (MAP, 35.5 ± 7.3 mm Hg); resuscitation raised MAP to >60 mm Hg by 26.5 ± 15.5 minutes. Shunt placement required 4.5 ± 1.8 minutes with no difference between groups. Four SUNDT thrombosed (three before 60 minutes). One SUNDT thrombosed at 240 minutes, and two TS-VIS and one TS-VISHep thrombosed between 230 and 282 minutes. Median patency was 21 minutes for SUNDT and 360 minutes for both TS-VIS groups (p = 0.04). While patent, all shunts maintained flow between 60% and 90% of contralateral., Conclusion: The TS-VIS demonstrated sustained patency superior to the Sundt under adverse hemodynamic conditions. No benefit was observed by the addition of localized heparin therapy over arterial pressure monitoring by the TS-VIS side port., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)