The Montana Interfacility Blood Network: A Novel Lifesaving "Hand-off" for the Optimal Care of Rural Patients.

Purpose: The state of Montana encompasses and defines rural health care as it is known in the United States (US) today. This vast area is punctuated by pockets of health care availability with varying access to blood products for transfusion. Furthermore, timely transport is frequently challenged by weather that may limit air transportation options, resulting in multiple hours in ground transport to definitive care. Patients and Methods: The Montana State Trauma Care Committee (MT-STCC) developed the Montana Interfacility Blood Network (MT-IBN) to ensure blood availability in geographically distanced cases where patients may otherwise not survive. The index case that led to the formal development of the MT-IBN is described, followed by a second case illustrating the IBN process. Results: This process and development manuscript details the innovative efforts of MT-STCC to develop this fledgling idea unique to rural US health care. We review guidelines that have been developed to define broad aspects of the MT-IBN including the reason to share resources, proper packaging, paperwork necessary for transfer, and how to provide resources directly to the patient. Finally, we describe implementation within the state. Conclusion: The MT-IBN was developed by MT-STCC to facilitate the hand-off of lifesaving blood to patients being transported by ground to definitive care in Montana without having to stop at an intermediary facility. This has already led to lives saved in areas that are limited in blood availability due to rurality.

Outcomes in necrotizing soft tissue infections are worse in rural versus urban Montana: a 10-year single center retrospective review.

Time to definitive surgical debridement has been recognized as a predictor for morbidity and mortality in necrotizing soft-tissue infections (NSTI). Rural patients are at particular risk due to limited local resources, decreased access to care, and prolonged transport times. The aim of the current study was to examine the outcomes of NSTI requiring surgical treatment in a previously non-described setting. This retrospective study (2010-2020) from a single tertiary care center in Montana reviewed patients ≥18 years old with a NSTI via ICD9/10 codes. Rural-Urban Continuum Codes (RUCC; characterizing counties by population size) were used to distinguish urban versus rural counties. Race (White and American Indian/Alaskan Native (AI/AN)) was self-described. Qualitative and quantitative comparisons between groups were determined using the appropriate two-tailed statistical tests. An aggregate of 177 patients was identified. Mean age in AI/AN was significantly lower (P<0.0001) compared to White patients with no preexisting condition delineation. NSTI demonstrated an elevated incidence in both rural areas and AI/AN patients. Diabetes was also significantly higher (P=0.0073) in rural versus urban patients. Both rural and AI/AN patients faced extended travel distance for treatment. AI/AN patients had a significantly different infection location than White. Furthermore, polymicrobial species were significantly more prevalent in AI/AN patients. Morbidities (defined as septic shock and/or amputation) were significantly higher in AI/AN patients and rural environments (P<0.01). There was no significant difference in all-cause mortality between respective groups. The state of Montana presents unique challenges to optimizing NSTI treatment due to excessive distances to regional tertiary care facilities. This delay in treatment can lead to increased morbidity.

A retrospective comparison of the emergent use of fixed-dose four-factor prothrombin complex versus weight-based dosing for intracranial hemorrhage assessing medication delivery time and cost.

OBJECTIVES: The goal of this study was to evaluate a low fixed-dose versus weight-based dosing strategy for four-factor prothrombin complex (4F-PCC) time to administration in intracranial hemorrhage (ICH) patients. METHODS: A retrospective analysis was conducted at a single rural Tertiary referral center in patients ≥18 years old on warfarin with ICH who received 4F-PCC. Continuous variables were summarized using mean (±95% CI) and compared using two-tailed tests; p values ≤0.05 were considered statistically significant. RESULTS: A total of 46 ICH patients were reversed using 4F-PCC (Fixed, n = 27 and Weight, n = 19). Baseline characteristics were equivalent. Total units of 4F-PCC (mean dose units 2525.1 versus 1623.3) and dose per kg were significantly reduced in the fixed-dose group. Total time from order to delivery was significantly reduced with the fixed-dose strategy (mean time 43.0 versus 29.0 minutes). Hospital length of stay (LOS), intensive care unit LOS, and mortality were equivalent with a similar mechanism. International Normalized Ratio (INR) reversal success (≤1.5) and total INR change was comparable with no difference in adverse thromboses between groups. CONCLUSIONS: A fixed-dosed strategy reduced time to 4F-PCC administration for warfarin reversal in ICH, as compared to a weight-based strategy; with no increase in LOS, mortality, or need for additional dosing. This also resulted in significant cost savings.

Bringing Trauma Education to the Frontier: Overcoming Distance Barriers Utilizing a Virtual Platform.

BACKGROUND: The American College of Surgeons and state regulations mandate that trauma facilities offer trauma-specific continuing education throughout the region they serve. These requirements come with unique challenges when serving a rural and sparsely populated state. A novel approach to providing education was necessitated by the coronavirus disease 2019 pandemic, travel distance, and limited local specialists. OBJECTIVE: The purpose of this article is to describe the development of a virtual educational program used to improve access to quality trauma education and decrease barriers to obtaining continuing education hours inherent in the region. METHODS: This article describes the development and implementation of the Virtual Trauma Education program, which provided one free continuing education hour per month from October 2020 to October 2021. The program reached more than 2,000 viewers and established a method to provide continuous monthly educational offerings throughout the region. RESULTS: After the Virtual Trauma Education program implementation, monthly educational attendance increased from an average of 55 to 190. Viewership data indicate that trauma education across our region is far more robust, available, and accessible using a virtual platform. With more than 2,000 views from October 2020 to October 2021, Virtual Trauma Education offerings have spread far beyond regional borders, reaching 25 states and 169 communities. CONCLUSION: Virtual Trauma Education delivers easily accessible trauma education and is a program that has proven its sustainability.

ATTAC! Development of a Novel Advanced Trauma Team Application Course.

BACKGROUND: Although existing trauma nurse courses provide basic education, advanced courses with simulation experiences that enhance team leadership, communication, and workflows are lacking. OBJECTIVE: To design and implement the Advanced Trauma Team Application Course (ATTAC) to promote advanced skills for nurses and respiratory therapists with varied experience and skill levels. METHODS: Trauma nurses and respiratory therapists were selected to participate based on years of experience and the novice to expert nurse model. Two nurses from each level (excluding novice) participated, ensuring a diverse cohort to promote development and mentorship. The 11-module course was presented over 12 months. A five-question survey was employed at the end of each module to self-evaluate assessment skills, communication skills, and comfort for trauma patient care. Participants rated skills and comfort on a "0-10" scale, with 0 being "not at all" to 10 being "extensively." RESULTS: The pilot course was conducted from May 2019 to May 2020 at a Level II trauma center in the Northwest United States. Nurses reported ATTAC improved assessment skills, team communication, and comfort in caring for trauma patients (mean = 9.4; 95% CI [9.0, 9.8]; scale of 0-10). Participants indicated scenarios closely mimicked real-world situations; concept application commenced directly following each session. CONCLUSION: This novel approach to advanced trauma education promotes development of advanced skills that enable nurses to anticipate needs rather than being reactive, engage in critical thinking, and adapt to rapidly changing patient conditions.

Biodegradable temporising matrix: use of negative pressure wound therapy shows a significantly higher success rate.

OBJECTIVE: The purpose of this case series was to evaluate the efficacy of a synthetic biodegradable temporising matrix (BTM; PolyNovo Biomaterials Pty Ltd, Australia) and compare the outcome of BTM patients with and without negative pressure wound therapy (NPWT). METHOD: A retrospective chart review was conducted on patients admitted with deep full-thickness burns, traumatic or complex wound injuries treated with BTM. Electronic medical records and images were evaluated by a team of clinical professionals. Endpoints included: the measure of successful BTM integration; and comparison between patients treated with and without NPWT. Additional measures were BTM total surface area, BTM sites, timeliness of BTM application and any complications. RESULTS: A total of 28 patients were evaluated and 23 (82.1%) demonstrated overall successful BTM integration. Patients treated with BTM in conjunction with NPWT (n=16) demonstrated a significantly higher (p=0.046) integration rate compared to patients treated without NPWT (n=12) (93.8% versus 58.3%, respectively). Patients treated with BTM with NPWT continued to successfully integrate and sustain favourable outcomes despite the presence of severe infection or the development of haematomas. CONCLUSION: A significantly higher integration rate was demonstrated when BTM was used in conjunction with NPWT. The results of this study further support the efficacy of successful integration of BTM as a replacement for tissue loss in the treatment of deep, full-thickness burns, traumatic and complex wound injuries, and particularly favourable outcomes with the use of NPWT. To the best of our knowledge, this is the first reported case series comparing the clinical outcomes of BTM with and without the use of NPWT.

Open Reduction and Internal Fixation of a Pediatric Talar Body Fracture using a Medial Malleolar Osteotomy - A Case Report.

Introduction: Talus fracture injuries are rare and most literature pertains to fractures in skeletally mature adults. It is unusual for pediatric talus fractures to be treated operatively and is normally treated with immobilization. The location of the talus fracture required a medial malleolar osteotomy to facilitate exposure and reduction, which was fixed with temporary smooth K-wires. The authors were unable to identify a previous description of this technique in the literature. Case Report: An 11-year-old female was referred to our hospital due to polytraumatic injuries sustained in a roll-over MVC. A displaced fracture of the talus body was present. Due to the fracture location, a medial malleolar osteotomy was required for exposure. An open reduction and internal fixation was performed using subchondral minifragment screws under general anesthesia. The patient healed uneventfully, regained a normal gait and full, pain-free range of motion. Conclusions: Medial malleolar osteotomy with smooth K-wire fixation appears to be a safe method for gaining access to the talus when required for reduction and/or fixation of pediatric talus fractures.

Post-burn temporal dynamics of blood plasma histamine during the initial 6 days from injury.

BACKGROUND: Burn injuries can induce distinct, systemic inflammatory and immunological responses which occur acutely up to 72 hrs or chronically after 24 hrs. Previously published literature showed a dramatic increase in whole blood histamine values within 24 hrs of a thermal injury. However, the data is limited due to infrequent monitoring, resulting in statistically insignificant findings. The goal of this study was to determine localized histamine fluctuations for 6 consecutive days in a successive group of patients admitted immediately after a burn. METHOD: Using blood plasma from 7 patients (average total burn surface area 24.7%), we examined histamine within an average 4.1 (± 0.3) hrs from burn injury, by means of a monoclonal-based competitive binding enzyme immunoassay. Histamine values were normalized to patient baselines prior to determining overall averages. Patient vitals and electrolyte values were extracted from the electronic health record. A two-tailed student t-test was used to compare values with p-value ≤ 0.05 considered statistically significant using statistical software R. RESULTS: The histamine values were significantly higher than patient baseline values up to 48 hrs (p-value ≤ 0.05), followed by a return to baseline values from approximately 3 days post-injury. Heart rates were within normal values up until 72 hrs. Hematocrit and hemoglobin began within normal values, dropped at 72 hrs, and reduced significantly from 96 hrs post-injury. The electrolyte calcium began within the normal range, and then was significantly less than the baseline value from 96 hrs post-injury. CONCLUSIONS: We have shown a distinct and significant increase in histamine plasma levels within 48 hrs after a moderate burn injury.

Treatment of a Full-Thickness Burn Injury With NovoSorb Biodegradable Temporizing Matrix and RECELL Autologous Skin Cell Suspension: A Case Series.

Dermal substitutes coupled with split thickness skin graft are the primary method of treating most severe full-thickness burns particularly when there is a lack of healthy donor skin. Although dermal replacements optimize functional and aesthetic outcomes in patients, the risk of infection and the amount of time required to process most dermal substitutes delay treatment potentially compromising graft take and the overall healing process. The purpose of this case series is to describe the treatment course of patients with severe burn injuries using a novel synthetic Biodegradable Temporizing Matrix (NovoSorb BTM) in conjunction with RECELL Autologous Cell Harvesting Device, a new methodology allowing for a timely point-of-care preparation of an autologous skin cell suspension in combination with a 3:1 split-thickness skin graft. To the best of our knowledge, this is the first reported case series to describe the treatment algorithm and clinical outcomes of deep full-thickness burns utilizing BTM in conjunction with RECELL ASCS.

Impact of duplicate CT scan rate after implementation of transfer image repository system at a level 1 trauma center.

PURPOSE: The regionalization of trauma in the USA results in frequent transfers of patients from a primary hospital ED to a higher level trauma facility. While many hospitals have a Picture Archive Communication System (PACS) which captures digital radiological images, these are often not available to the receiving institution resulting in duplicate imaging. The state of Arkansas instituted a trauma image repository (TIR) in July 2013. We examined whether implementation of this repository would impact CT scan duplication in the trauma system. METHODS: This was a retrospective analysis of trauma patients transferred from outlying hospitals in Arkansas and Missouri to a single level 1 trauma hospital in Missouri between July 2012 and June 2015. We compared the duplicate CT rate for patients transferred from Arkansas and Missouri hospitals before and after the repository was implemented for Arkansas. RESULTS: Prior to implementation (July 2012-June 2013) of Arkansas TIR, duplicate CT rates were similar for patients transferred from Arkansas (11.5% ± 2.8) or Missouri (16.3% ± 7.5). Following implementation (July 2013-June 2014), the duplicate CT rate for patients transferred from Arkansas was significantly lower (Arkansas = 10.1% vs. Missouri 16.2%; CI 95%, p = 0.02), and significance continued (Arkansas = 9.0% vs. Missouri = 17.8%; CI 95%, p = 0.02) during follow-up (July 2014-June 2015). CONCLUSION: Fewer patients received duplicated scans within the Arkansas as compared with the Missouri-based trauma referral systems regardless of Injury Severity Scores (ISS). Our findings suggest that TIR adoption coupled with PACS improved transferability of radiographic studies and could improve patient care while reducing costs in trauma transfers.

Total Retinal Blood Flow in a Nonhuman Primate Optic Nerve Transection Model Using Dual-Beam Bidirectional Doppler FD-OCT and Microsphere Method.

PURPOSE: We validated noninvasive Doppler-optical coherence tomography (OCT) blood flow measurements against the terminal microsphere method in a surgical induced optic nerve transection nonhuman primate model. METHODS: In 6 nonhuman primates, total retinal blood flow (TRBF) was measured with a custom-built dual-beam bidirectional Doppler Fourier Domain (FD)-OCT. Peripapillary retinal nerve fiber layer thickness (RNFLT) was measured by Spectralis spectral-domain (SD)-OCT. Measurements were performed every 10 to 15 days before and after unilateral optic nerve transection (ONT) until RNFLT was reduced by more than 40% from baseline. Before the animals were killed, TRBF was measured using the microsphere technique. RESULTS: A significant correlation between all arterial and venous Doppler OCT TRBF measurements was found in ONT and contralateral control eyes (both P < 0.01, n = 6). The Bland-Altman analysis showed a bias of 0.57 in the ONT group and 0.02 in the contralateral control group. Also, excellent agreement was observed between Doppler OCT and microsphere measurements (P < 0.01, r = 0.976, bias = 0.54). After ONT, TRBF and RNFLT decreased by -51% ± 42% and -44% ± 2% (n = 5), respectively. In the contralateral control eyes, TRBF and RNFLT were unchanged. CONCLUSIONS: Very good accordance was found between TRBF measurements, obtained with dual-beam bidirectional Doppler FD-OCT and the microsphere method. It also was possible to monitor changes over time in TRBF after ONT with Doppler OCT. These findings highlight the accuracy and potential of noninvasive Doppler OCT to provide valuable information for detecting early changes in ocular disease in future.

MicroRNA responses to focal cerebral ischemia in male and female mouse brain.

Stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage resulting from an ischemic event compared to females. Previous studies revealed that microRNA (miRNA) expression is regulated by cerebral ischemia in males; however, no studies to date have examined the effect of ischemia on miRNA responses in females. Thus, we examined miRNA responses in male and female brain in response to cerebral ischemia using miRNA arrays. These studies revealed that in male and female brains, ischemia leads to both a universal miRNA response as well as a sexually distinct response to challenge. Target prediction analysis of the miRNAs increased in male or female ischemic brain reveal sex-specific differences in gene targets and protein pathways. These data support that the mechanisms underlying sexually dimorphic responses to cerebral ischemia includes distinct changes in miRNAs in male and female brain, in addition to a miRNA signature response to ischemia that is common to both.

Effect of (S)-3,5-DHPG on microRNA expression in mouse brain.

MicroRNAs are small non-coding RNAs that regulate post-transcriptional gene expression. In the short time since the discovery of microRNAs, the literature has burgeoned with studies focused on the biosynthesis of microRNAs, target prediction and binding, and mechanisms of translational repression by microRNAs. Given the prominent role of microRNAs in all areas of cell biology, it is not surprising that microRNAs are also linked to human diseases, including those of the nervous system. One of the least-studied areas of microRNA research is how their expression is regulated outside of development and cancer. Thus, we examined a role for regulation of microRNAs by neurotransmitter receptor activation in mouse brain. We focused on the group I metabotropic glutamate receptors by using intracerebroventricular injection of the selective agonist, (S)-3,5-dihydroxyphenylglycine (DHPG) in mouse brain. We then examined the expression of microRNAs in the cerebral cortex by Ambion and Invitrogen microarrays, and the expression of mature microRNA sequences by SABiosciences qPCR arrays, at 4, 8 and 24 h after DHPG injection. These studies revealed that the largest number of significantly regulated microRNAs was detected 8h after DHPG injection in the microarrays and qPCR arrays. We then used RNA blots to quantify microRNA expression, and in situ hybridization to examine cellular distribution of the microRNAs regulated by DHPG. Bioinformatic analysis of the microRNAs regulated 8 h after DHPG in all three arrays revealed KEGG pathways that are known to correlate with group I mGluR effects, as well as recently described and novel pathways. These studies are the first to show that DHGP regulates the expression of microRNAs in mouse cerebral cortex, and support the hypothesis that group I mGluRs may regulate microRNA expression in mouse brain.

Suppression of TNF receptor-1 signaling in an in vitro model of epileptic tolerance.

Tumor necrosis factor-α (TNFα) is a pleiotropic cytokine that can regulate cell survival, inflammation or, under certain circumstances, trigger cell death. Previous work in rat seizure models and analysis of temporal lobe samples from epilepsy patients has suggested seizures activate TNF receptor 1 (TNFR1). Here we explored the activation and functional significance of TNFR1 signaling in the mouse hippocampus using in vitro and in vivo models of seizure-induced neuronal injury. Focal-onset status epilepticus in mice upregulated TNFR1 levels and led to formation of TNFR1-TNFR-associated death domain (TRADD) and TRADD-Fas-associated death domain (FADD) binding. Seizure-like injury modeled in vitro by removal of chronic excitatory blockade in mouse hippocampal neurons also activated this TNFR1 signaling pathway. Prior exposure of hippocampal neurons to a non-harmful seizure episode, via NMDA receptor blockade, 24 h prior to injurious seizures significantly reduced cell death and modeled epileptic tolerance in vitro. TNFR1 complex formation with TRADD and TRADD-FADD binding were reduced in tolerant cells. Finally, TNFR1 signaling and cell death were reduced by PKF-242-484, a dual matrix metaloproteinase/TNFα converting enzyme inhibitor. The present study shows that TNFR1 signaling is activated in mouse seizure models and may contribute to neuropathology in vitro and in vivo while suppression of this pathway may underlie neuroprotection in epileptic tolerance.

Sumo-2/3-ylation following in vitro modeled ischemia is reduced in delayed ischemic tolerance.

Several recent studies suggest that sumo-2/3 modification of proteins occurs following harmful ischemia, however, sumo-2/3-ylation may also be associated with hibernation-mediated neuroprotection. Here we investigate the sumoylation of proteins following ischemia and ischemic tolerance using our established in vitro model of ischemia (oxygen and glucose deprivation; OGD). Following harmful ischemia (120 min OGD), we observed a significant increase in the sumo-2/3-ylation of high molecular weight proteins (>85 kDa), but not sumo-1-ylation of proteins. Sumo-2/3-ylation following 120 min OGD was reduced when cultures were preconditioned with non-harmful 30 min OGD 24 h earlier (delayed ischemic tolerance). However, we observed no change in sumo-2/3-ylation in a model of rapid ischemic tolerance. The effects of preconditioning on sumo-2/3-ylation following harmful ischemia were blocked by the protein synthesis inhibitor cycloheximide (1.0 muM), a known inhibitor of delayed ischemic tolerance. In addition, we observed a reduction in sumo-2/3-ylation using hypothermia (4 degrees C 30 min) as the preconditioning stimuli to induce delayed ischemic tolerance. Further studies show that sumo-2/3-ylation occurs during the ischemic insult and that preconditioning does not change expression of the sumo E1- and E2-ligases (UBA2 and Ubc9) or the sumo specific isopeptidases (SenP1-3). While sumo-2/3-ylation is enhanced under conditions of cell stress, it is not yet clear whether this is a cause or consequence of harmful ischemia-induced cell damage.

Ubiquitin-proteasome system as a modulator of cell fate.

The ubiquitin-proteasome system is the major non-lysosymal system for degrading proteins in the cell; the work leading to its discovery was awarded the Nobel Prize in Chemistry in 2004. In addition to small ubiquitin-like modifiers (e.g. Sumo and Nedd8), ubiquitin is involved in the complex regulation of the levels and function of many proteins and signaling pathways involved in determining cell fate. The cell death regulatory proteins, such as Bcl-2 family proteins and caspases are targeted for degradation by the ubiquitin proteasome system (UPS). In addition to mediating the degradation of proteins, the UPS regulates function and translocation of proteins, many of which play a role in the determination of cell fate. For example the UPS can regulate the activity of transcription factors, such as P53, NF-kappaB and HIF-1 alpha, which control the expression of protein mediators of cell death. Aberrant UPS function has been reported in multiple neuropathologies including Parkinson's diseases and ischemia. With the number of ubiquitin conjugating and de-conjugating enzymes reaching close to the levels of protein kinases and phosphatases, it is clear that ubiquitination is an important biological regulatory step for proteins.

Isolated plant mitochondria import chloroplast precursor proteins in vitro with the same efficiency as chloroplasts.

Most chloroplast and mitochondrial proteins are synthesized with N-terminal presequences that direct their import into the appropriate organelle. In this report we have analyzed the specificity of standard in vitro assays for import into isolated pea chloroplasts and mitochondria. We find that chloroplast protein import is highly specific because mitochondrial proteins are not imported to any detectable levels. Surprisingly, however, pea mitochondria import a range of chloroplast protein precursors with the same efficiency as chloroplasts, including those of plastocyanin, the 33-kDa photosystem II protein, Hcf136, and coproporphyrinogen III oxidase. These import reactions are dependent on the Deltaphi across the inner mitochondrial membrane, and furthermore, marker enzyme assays and Western blotting studies exclude any import by contaminating chloroplasts in the preparation. The pea mitochondria specifically recognize information in the chloroplast-targeting presequences, because they also import a fusion comprising the presequence of coproporphyrinogen III oxidase linked to green fluorescent protein. However, the same construct is targeted exclusively into chloroplasts in vivo indicating that the in vitro mitochondrial import reactions are unphysiological, possibly because essential specificity factors are absent in these assays. Finally, we show that disruption of potential amphipathic helices in one presequence does not block import into pea mitochondria, indicating that other features are recognized.