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1.
Mil Med ; 189(Supplement_3): 190-195, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160793

ABSTRACT

INTRODUCTION: The association between hypothermia, coagulopathy, and acidosis in trauma is well described. Hypothermia mitigation starts in the prehospital setting; however, it is often a secondary focus after other life-saving interventions. The deployed environment further compounds the problem due to prolonged evacuation times in rotary wing aircraft, resource limitations, and competing priorities. This analysis evaluates hypothermia in combat casualties and the relationship to resuscitation strategy with blood products. METHODS: Using the data from the Department of Defense Joint Trauma Registry from 2003 to 2021, a retrospective analysis was conducted on adult trauma patients. Inclusion criteria was arrival at the first military treatment facility (MTF) hypothermic (<95ºF). Study variables included: mortality, year, demographics, battle vs non-battle injury, mechanism, theater of operation, vitals, and labs. Subgroup analysis was performed on severely injured (15 < ISS < 75) hypothermic trauma patients resuscitated with whole blood (WB) vs only component therapy. RESULTS: Of the 69,364 patients included, 908 (1.3%) arrived hypothermic; the vast majority of whom (N = 847, 93.3%) arrived mildly hypothermic (90-94.9°F). Overall mortality rate was 14.8%. Rates of hypothermia varied by year from 0.7% in 2003 to 3.9% in 2014 (P <0.005). On subgroup analysis, mortality rates were similar between patients resuscitated with WB vs only component therapy; though base deficit values were higher in the WB cohort (-10 vs -6, P < 0.001). CONCLUSION: Despite nearly 20 years of combat operations, hypothermia continues to be a challenge in military trauma and is associated with a high mortality rate. Mortality was similar between hypothermic trauma patients resuscitated with WB vs component therapy, despite greater physiologic derangements on arrival in patients who received WB. As the military has the potential to conduct missions in environments where the risk of hypothermia is high, further research into hypothermia mitigation techniques and resuscitation strategies in the deployed setting is warranted.


Subject(s)
Hypothermia , Humans , Hypothermia/complications , Hypothermia/etiology , Retrospective Studies , Male , Female , Adult , Registries/statistics & numerical data , Resuscitation/methods , Resuscitation/statistics & numerical data , Resuscitation/trends , Military Personnel/statistics & numerical data , Wounds and Injuries/complications , Wounds and Injuries/therapy
2.
Surg Innov ; : 15533506241275288, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39151929

ABSTRACT

BACKGROUND: Early detection of abdominal hemorrhage via ultrasound has life-saving implications for military and civilian trauma. However, strict adherence to light discipline may prohibit the use of ultrasound devices in the deployed setting. Additionally, current night vision devices remain noncompatible with ultrasound technology. This study sought to assess an innovative night vision device with ultrasound capable picture-in-picture display via a intraabdominal hemorrhage model to identify noncompressible truncal hemorrhage in blackout conditions. METHODS: 8 post mortem fetal porcine specimens were used and divided into 2 groups: intrabdominal hemorrhage (n = 4) vs no hemorrhage (n = 4). Intrabdominal hemorrhage was modeled via direct injection of 200 mL of normal saline into the peritoneal cavity. Under blackout conditions, 5 participants performed a focused assessment with sonography for trauma (FAST) exam on each model using the prototype ultrasound-capable night vision device. RESULTS: Of the 40 FAST exams performed, 95% (N = 38) resulted in the correct identification of intraabdominal hemorrhage. Of the incorrectly identified exams, both were false positives resulting in a 100% sensitivity, 90% specificity, 91% positive predictive value, and a 100% negative predictive value. All participants noted the novel device was easy to use and provided superior visualization for performing FAST exams under blackout conditions. CONCLUSION: The ultrasound-enabled night vision prototype demonstrated promising results in identifying noncompressible truncal hemorrhage while maintaining strict light discipline in blackout conditions. Further research efforts should be directed at assessing the ability of providers to perform procedures in blackout conditions using the ultrasound-enabled prototype night vision device.

3.
Article in English | MEDLINE | ID: mdl-38689383

ABSTRACT

BACKGROUND: Whole blood (WB) transfusions in trauma represent an increasingly utilized resuscitation strategy in trauma patients. Previous reports suggest a probable mortality benefit with incorporating WB into massive transfusion protocols. However, questions surrounding optimal WB practices persist. We sought to assess the association between the proportion of WB transfused during the initial resuscitative period and its impact on early mortality outcomes for traumatically injured patients. METHODS: We performed a retrospective analysis of severely injured patients requiring emergent laparotomy and ≥ 3 units of red blood cell containing products (WB or packed red blood cells) within the first hour from an ACS Level 1 Trauma Center (2019-2022). Patients were evaluated based on the proportion of WB they received compared to packed red blood cells during their initial resuscitation (high ratio cohort ≥50% WB vs low ratio cohort <50% WB). Multilevel Bayesian regression analyses were performed to calculate the posterior probabilities and risk ratios (RR) associated with a WB predominant resuscitation for early mortality outcomes. RESULTS: 266 patients were analyzed (81% male, mean age of 36 years old, 61% penetrating injury, mean ISS of 30). The mortality was 11% at 4-hours and 14% at 24-hours. The high ratio cohort demonstrated a 99% (RR 0.12; 95% CrI 0.02-0.53) and 99% (RR 0.22; 95% CrI 0.08-0.65) probability of decreased mortality at 4-hours and 24-hours, respectively, compared the low ratio cohort. There was a 94% and 88% probability of at least a 50% mortality relative risk reduction associated with the WB predominate strategy at 4 hours and 24 hours, respectively. CONCLUSION: Preferential transfusion of WB during the initial resuscitation demonstrated a 99% probability of being superior to component predominant resuscitations with regards to 4 and 24-hour mortality suggesting that WB predominant resuscitations may be superior for improving early mortality. Prospective, randomized trials should be sought. LEVEL OF EVIDENCE: Therapeutic, Level III.

4.
Am J Surg ; 231: 100-105, 2024 May.
Article in English | MEDLINE | ID: mdl-38461066

ABSTRACT

INTRODUCTION: Mortality rates among hypotensive civilian patients requiring emergent laparotomy exceed 40%. Damage control (DCR) principles were incorporated into the military's Clinical Practice Guidelines (CPG) in 2008. We examined combat casualties requiring emergent laparotomy to characterize how mortality rates compare to hypotensive civilian trauma patients. METHODS: The DoD Trauma Registry (2004-2020) was queried for adults who underwent combat laparotomy. Patients who were hypotensive were compared to normotensive patients. Mortality was the outcome of interest. Mortality rates before (2004-2007) and after (2009-2020) DCR CPG implementation were analyzed. RESULTS: 1051 patients were studied. Overall mortality was 6.5% for normotensive casualties and 28.7% for hypotensive casualties. Mortality decreased in normotensive patients but remained unchanged in hypotensive patients following the implementation of the DCR CPG. CONCLUSION: Hypotensive combat casualties undergoing emergent laparotomy demonstrated a mortality rate of 29.5%. Despite many advances, mortality rates remain high in hypotensive patients requiring emergent laparotomy.


Subject(s)
Hypotension , Laparotomy , Adult , Humans , Registries , Retrospective Studies
5.
Am J Surg ; 231: 60-64, 2024 May.
Article in English | MEDLINE | ID: mdl-37173166

ABSTRACT

BACKGROUND: Surgical Site Infections (SSI) yield subtle, early signs that are not readily identifiable. This study sought to develop a machine learning algorithm that could identify early SSIs based on thermal images. METHODS: Images were taken of surgical incisions on 193 patients who underwent a variety of surgical procedures. Two neural network models were generated to detect SSIs, one using RGB images, and one incorporating thermal images. Accuracy and Jaccard Index were the primary metrics by which models were evaluated. RESULTS: Only 5 patients in our cohort developed SSIs (2.8%). Models were instead generated to demarcate the wound site. The models had 89-92% accuracy in predicting pixel class. The Jaccard indices for the RGB and RGB â€‹+ â€‹Thermal models were 66% and 64%, respectively. CONCLUSIONS: Although the low infection rate precluded the ability of our models to identify surgical site infections, we were able to generate two models to successfully segment wounds. This proof-of-concept study demonstrates that computer vision has the potential to support future surgical applications.

6.
Mil Med ; 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37995270

ABSTRACT

INTRODUCTION: Simple mastectomies are routinely performed in the military health care system as gynecomastia can cause significant pain and discomfort when wearing body armor. Postoperative recovery negatively impacts personnel readiness. In this study, we sought to study time to return to duty in active duty service members who undergo surgery for gynecomastia. METHODS AND MATERIALS: We conducted a single-center retrospective review of active duty patients undergoing a surgical operation for gynecomastia from July 2020-June 2022. A total of 96 patients were included. Our primary outcome of interest was time from surgery to return to duty. A multivariate analysis was performed to assess for factors independently associated with surgical complications including patient demographics and operative techniques. RESULTS: The median number of days to return to duty after surgery was 28 days (IQR 13-37). The median loss of duty days because of gynecomastia without surgery was 19 days (IQR 10-21), which was different on the Mann-Whitney U test. Surgical complications were observed in 19 patients (19.7%) with the most common complications being seroma (11), hematoma (4), nipple-areolar complex necrosis (2), and infection (2). Patients with a complication have significantly more time to return to duty (28 vs. 49 days, P < .001). Risk factors associated with an increased risk of complication include ranks E1-E4, behavioral health diagnosis, "open" vs. "combined" technique with liposuction, length of operation greater than 58 minutes, and excised breast mass greater than 17.9 g. CONCLUSIONS: Gynecomastia surgery is associated with a detriment to personnel readiness. Surgery should be reserved for patients with severe symptoms that prevent the performance of daily duties. Furthermore, factors associated with an increased risk for complications include ranks E1-E5, behavioral health diagnosis, length of operation >58 minutes, and excised breast mass >17.9 g. The operating surgeon should be mindful of these factors.

7.
Int J Mol Sci ; 24(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37239814

ABSTRACT

Recombinant engineering for protein production commonly employs plasmid-based gene templates for introduction and expression of genes in a candidate cell system in vitro. Challenges to this approach include identifying cell types that can facilitate proper post-translational modifications and difficulty expressing large multimeric proteins. We hypothesized that integration of the CRISPR/Cas9-synergistic activator mediator (SAM) system into the human genome would be a powerful tool capable of robust gene expression and protein production. SAMs are comprised of a "dead" Cas9 (dCas9) linked to transcriptional activators viral particle 64 (VP64), nuclear factor-kappa-B p65 subunit (p65), and heat shock factor 1 (HSF1) and are programmable to single or multiple gene targets. We integrated the components of the SAM system into human HEK293, HKB11, SK-HEP1, and HEP-g2 cells using coagulation factor X (FX) and fibrinogen (FBN) as proof of concept. We observed upregulation of mRNA in each cell type with concomitant protein expression. Our findings demonstrate the capability of human cells stably expressing SAM for user-defined singleplex and multiplex gene targeting and highlight their broad potential utility for recombinant engineering as well as transcriptional modulation across networks for basic, translational, and clinical modeling and applications.


Subject(s)
CRISPR-Cas Systems , Transcription Factors , Humans , CRISPR-Cas Systems/genetics , HEK293 Cells , Transcription Factors/genetics , Transcriptional Activation , Recombinant Proteins/genetics , Gene Editing
8.
Am J Surg ; 225(5): 909-914, 2023 05.
Article in English | MEDLINE | ID: mdl-37059641

ABSTRACT

INTRODUCTION: Medical operations are vulnerable to global supply chain fluctuations. The ability to locally produce and reliably sterilize medical equipment may mitigate this risk. This project developed a reliable high-level disinfection process for 3D printed surgical tools. METHODS: Surgical instruments and consumables were designed and printed from various materials. Devices contaminated with known and unknown bacteria underwent one of three cleaning methods followed by high-level disinfection using submersion in a Cidex OPA Solution. Devices were then cultured on blood agar plates and incubated for 48 h. Positive and negative controls were performed. RESULTS: The results of control experiments showed no growth on negative controls and significant growth on all positive control plates. Of the three cleaning methods tested, one showed no growth: cleaning with isopropyl alcohol and chlorhexidine followed by Cidex bath. DISCUSSION: This project successfully developed a rapid high-level disinfection process for 3D printed surgical instruments made from two different types of 3D printing material.


Subject(s)
Disinfection , Sterilization , Humans , Glutaral , Sterilization/methods , Disinfection/methods , Chlorhexidine , Printing, Three-Dimensional , Surgical Instruments , Equipment Contamination/prevention & control
9.
Transfusion ; 63 Suppl 3: S96-S104, 2023 05.
Article in English | MEDLINE | ID: mdl-36970937

ABSTRACT

BACKGROUND: Innovative solutions to resupply critical medical logistics and blood products may be required in future near-peer conflicts. Unmanned aerial vehicles (UAVs) are increasingly being used in austere environments and may be a viable platform for medical resupply and the transport of blood products. METHODS: A literature review on PubMed and Google Scholar up to March of 2022 yielded a total of 27 articles that were included in this narrative review. The objectives of this article are to discuss the current limitations of prehospital blood transfusion in military settings, discuss the current uses of UAVs for medical logistics, and highlight the ongoing research surrounding UAVs for blood product delivery. DISCUSSION: UAVs allow for the timely delivery of medical supplies in numerous settings and have been utilized for both military and civilian purposes. Investigations into the effects of aeromedical transportation on blood products have found minimal blood product degradation when appropriately thermoregulated and delivered in a manner that minimizes trauma. UAV delivery of blood products is now actively being explored by numerous entities around the globe. Current limitations surrounding the lack of high-quality safety data, engineering constraints over carrying capacity, storage capability, and distance traveled, as well as air space regulations persist. CONCLUSION: UAVs may offer a novel solution for the transport of medical supplies and blood products in a safe and timely manner for the forward-deployed setting. Further research on optimal UAV design, optimal delivery techniques, and blood product safety following transport should be explored prior to implementation.


Subject(s)
Military Personnel , Transportation , Humans , Blood Transfusion , Pharmaceutical Preparations
10.
J Trauma Acute Care Surg ; 95(5): 679-684, 2023 11 01.
Article in English | MEDLINE | ID: mdl-36973876

ABSTRACT

INTRODUCTION: Traumatic pulmonary injuries are common in chest trauma. Persistent air leaks occur in up to 46% of patients depending on injury severity. Prolonged leaks are associated with increased morbidity and cost. Prior work from our first-generation pectin patches successfully sealed pulmonary leaks in a cadaveric swine model. We now test the next-generation pectin patch against wedge resection in the management of air leaks in anesthetized swine. METHODS: A continuous air leak of 10% to 20% percent was created to the anterior surface of the lung in intubated and sedated swine. Animals were treated with a two-ply pectin patch or stapled wedge resection (SW). Tidal volumes (TVs) were recorded preinjury and postinjury. Following repair, TVs were recorded, a chest tube was placed, and animals were observed for presence air leak at closure and for an additional 90 minutes while on positive pressure ventilation. Mann-Whitney U test and Fisher's exact test used to compare continuous and categorical data between groups. RESULTS: Thirty-one animals underwent either SW (15) or pectin patch repair (PPR, 16). Baseline characteristics were similar between animals excepting baseline TV (SW, 10.3 mL/kg vs. PPR, 10.9 mL/kg; p = 0.03). There was no difference between groups for severity of injury based on percent of TV loss (SW, 15% vs. PPR, 14%; p = 0.5). There was no difference in TV between groups following repair (SW, 10.2 mL/kg vs. PPR, 10.2 mL/kg; p = 1) or at the end of observation (SW, 9.8 mL/kg vs. PPR, 10.2 mL/kg; p = 0.4). One-chamber intermittent air leaks were observed in three of the PPR animals, versus one in the SW group ( p = 0.6). CONCLUSION: Pectin patches effectively sealed the lung following injury and were noninferior when compared with wedge resection for the management of acute traumatic air leaks. Pectin patches may offer a parenchymal sparing option for managing such injuries, although studies evaluating biodurability are needed.


Subject(s)
Lung Injury , Pneumonectomy , Humans , Animals , Swine , Lung/surgery , Lung Injury/surgery , Chest Tubes , Pectins , Postoperative Complications/surgery
11.
J Trauma Acute Care Surg ; 95(1): 55-61, 2023 07 01.
Article in English | MEDLINE | ID: mdl-36872522

ABSTRACT

INTRODUCTION: Injuries to the liver and small bowel are common in multiple injuries. While there are currently a variety of accepted damage-control techniques to expeditiously manage such injuries, morbidity and mortality remain high. Pectin polymers have previously been shown to effectively seal visceral organ injuries ex vivo through physiochemical entanglement with the glycocalyx. We sought to compare the standard of care for the management of penetrating liver and small bowel injuries with a pectin-based bioadhesive patch in a live animal model. METHODS: Fifteen adult male swine underwent a laparotomy with standardized laceration to the liver. Animals were randomized to one of three treatment arms: packing with laparotomy pads (n = 5), suture repair (n = 5), or pectin patch repair (n = 5). Following 2 hours of observation, fluid was evacuated from the abdominal cavity and weighed. Next, a full-thickness small bowel injury was created, and animals were randomized to either a sutured repair (n = 7) or pectin patch repair (n = 8). The segment of bowel was then pressurized with saline, and the burst pressure was recorded. RESULTS: All animals survived the protocol to completion. There were no clinically significant differences between groups regarding baseline vitals or laboratory studies. On one-way analysis of variance, there was a statistically significant difference between groups regarding blood loss after liver repair (26 mL suture vs. 33 mL pectin vs. 142 mL packing, p < 0.01). On post hoc analysis, there was no statistically significant difference between suture and pectin ( p = 0.9). After repair, small bowel burst pressures were similar between pectin and suture repair (234 vs. 224 mm Hg, p = 0.7). CONCLUSION: Pectin-based bioadhesive patches performed similarly to the standard of care for the management of liver lacerations and full-thickness bowel injuries. Further testing is warranted to assess the biodurability of a pectin patch repair, as it may offer a simple option to effectively temporize traumatic intra-abdominal injuries.


Subject(s)
Abdominal Cavity , Abdominal Injuries , Multiple Trauma , Animals , Male , Abdominal Injuries/surgery , Intestine, Small/surgery , Intestine, Small/injuries , Multiple Trauma/therapy , Pectins , Swine
12.
Surg Clin North Am ; 103(2): 287-298, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36948719

ABSTRACT

The evolution of the knowledge economy and technology industry have fundamentally changed the learning environments occupied by contemporary surgical trainees and created pressures that will force the surgical community to consider. Although some learning differences are intrinsic to the generations themselves, these differences are primarily a function of the environments in which surgeons of different generations trained. Acknowledgment of the principles of connectivism and thoughtful integration of artificial intelligence and computerized decision support tools must play a central role in charting the future course of surgical education.


Subject(s)
Artificial Intelligence , Surgeons , Humans , Learning
14.
Am J Surg ; 225(5): 897-902, 2023 05.
Article in English | MEDLINE | ID: mdl-36764898

ABSTRACT

INTRODUCTION: The Military Health System (MHS) is tasked with the dual mission of providing medical care to beneficiaries while ensuring medical readiness. MHS provides care through a combination of military treatment facilities (MTF) ("direct care"; DC) & off-base civilian facilities ("purchased care"; PC). Given recent concerns regarding low surgical volume at MTFs, we sought to evaluate COVID's impact on elective and non-elective case volume at MTFs with surgical residencies. METHODS: Retrospective review of 2017-2021 M2 database was performed on Tricare beneficiaries who underwent bariatric surgery or major colorectal surgery in the DC or PC market at, or, surrounding MTFs with surgical residencies. Procedures were identified using ICD-10 procedure codes and Medicare severity-diagnosis related groups. A detailed analysis was then performed on changes in case volume in the DC and PC markets. RESULTS: 5,698 bariatric and 5,517 major colorectal procedures were performed during the study period. There was an 84% vs 20% quarterly decrease in elective bariatric surgeries completed in the DC and PC markets from Q1 to Q2 2020. Pre to post-COVID (Q1 2017 - Q1 2020 vs Q3 2020 - Q4 2021) there was a decrease in the percentage of bariatric surgeries completed in the DC market (74.1% vs 55.0%, p = 0.001). Meanwhile, major colorectal surgery quarterly case volume remained unchanged in the DC (137 vs 125, p = 0.18) and PC (146 v 137, p = 0.13) markets, pre- and post-COVID. DISCUSSION: Bariatric surgical case volume at MTFs disproportionately decreased during COVID when compared to the PC market and major colorectal cases. Bariatric case volume has rebounded in PC markets surpassing pre-COVID levels while DC case volume remains depressed. Further attention is warranted regarding decreased elective surgical case volume at MTFs.


Subject(s)
Bariatric Surgery , COVID-19 , Colorectal Neoplasms , Internship and Residency , Aged , Humans , United States , Medicare , COVID-19/epidemiology , Retrospective Studies
15.
Mil Med ; 2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36458912

ABSTRACT

INTRODUCTION: With increasing global unrest and military physician shortages potentially leading to a surgeon draft, we sought to evaluate the readiness of graduating general surgery residents to care for casualties of war. MATERIALS AND METHODS: We evaluated the National Data Reports of Surgery Case Logs for general surgery residents from 2009 to 2018 to quantify experience with key procedures that provide critical skills required for wartime surgery. Reported cases from the Accreditation Council for Graduate Medical Education for graduating residents from civilian and military residency programs were analyzed for 28 individual procedures determined to be critical for the care of combat casualties. These included central and peripheral vascular procedures, as well as neck, thoracic, abdominal, and peripheral interventions. RESULTS: From 2009 to 2018, there has been a significant decrease in wartime-relevant cases by graduating residents. Notably, these include aorto-iliac/femoral bypasses (50% reduction; 7.1%/year; P < .001), femoral-popliteal bypasses (60% reduction; 6.9%/year; P < .001), femoral-femoral bypasses (30% reduction; 2.6%/year; P < .001), upper extremity amputations (50% reduction; 6.4%/year; P = .016), fasciotomies for trauma (50% reduction; 4.5%/year; P = .013), open repair of ruptured infrarenal aorto-iliac aneurysms (70% reduction; 5.8%/year; P < .001), repair of traumatic aorta or vena cava injuries (70% reduction; 7%/year; P = .007), carotid endarterectomies (40% reduction; 4%/year; P < .001), lung resections (40% reduction; 3.7%/year; P = .001), trauma splenectomies/splenorrhaphy (30% reduction; 2.9%/year; P < .001), and repair of traumatic liver lacerations (30% reduction; 2.5%/year; P = .036). CONCLUSIONS: Graduating general surgery residents has limited exposure to wartime critical skills due to a significant reduction in open vascular, head and neck, thoracic, and operative trauma cases. As the threat of global war persists and new graduates continue to deploy worldwide, residency training must be augmented to ensure adequate preparation in case a surgeon draft is required to fulfill demand for military surgeons.

16.
Mil Med ; 2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35730578

ABSTRACT

BACKGROUND: Identification of pediatric trauma patients at the highest risk for death may promote optimization of care. This becomes increasingly important in austere settings with constrained medical capabilities. This study aimed to develop and validate predictive models using supervised machine learning (ML) techniques to identify pediatric warzone trauma patients at the highest risk for mortality. METHODS: Supervised learning approaches using logistic regression (LR), support vector machine (SVM), neural network (NN), and random forest (RF) models were generated from the Department of Defense Trauma Registry, 2008-2016. Models were tested and compared to determine the optimal algorithm for mortality. RESULTS: A total of 2,007 patients (79% male, median age range 7-12 years old, 62.5% sustaining penetrating injury) met the inclusion criteria. Severe injury (Injury Severity Score > 15) was noted in 32.4% of patients, while overall mortality was 7.13%. The RF and SVM models displayed recall values of .9507 and .9150, while LR and NN displayed values of .8912 and .8895, respectively. Random forest (RF) outperformed LR, SVM, and NN on receiver operating curve (ROC) analysis demonstrating an area under the ROC of .9752 versus .9252, .9383, and .8748, respectively. CONCLUSION: Machine learning (ML) techniques may prove useful in identifying those at the highest risk for mortality within pediatric trauma patients from combat zones. Incorporation of advanced computational algorithms should be further explored to optimize and supplement the diagnostic and therapeutic decision-making process.

17.
Int J Mol Sci ; 23(9)2022 May 03.
Article in English | MEDLINE | ID: mdl-35563479

ABSTRACT

Current hemostatic agents are obtained from pooled plasma from multiple donors requiring costly pathogen screening and processing. Recombinant DNA-based production represents an engineering solution that could improve supply, uniformity, and safety. Current approaches are typically for single gene candidate peptides and often employ non-human cells. We devised an approach where multiple gene products could be produced from a single population of cells. We identified gene specific Synergistic Activation Mediators (SAM) from the CRISPR/Cas9 system for targeted overexpression of coagulation factors II, VII, IX, X, and fibrinogen. The components of the CRISPR-SAM system were expressed in Human Embryonic Kidney Cells (HEK293), and single (singleplex) or multi-gene (multiplex) upregulation was assessed by quantitative RT-PCR (qRT-PCR) and protein expression by ELISA analysis. Factor II, VII, IX, and X singleplex and multiplex activation resulted in 120-4700-fold and 60-680-fold increases in gene expression, respectively. Fibrinogen sub-unit gene activation resulted in a 1700-92,000-fold increases and 80-5500-fold increases in singleplex or multiplex approaches, respectively. ELISA analysis showed a concomitant upregulation of candidate gene products. Our findings demonstrate the capability of CRISPR/Cas9 SAMs for single or multi-agent production in human cells and represent an engineering advance that augments current recombinant peptide production techniques.


Subject(s)
Blood Coagulation Factors , CRISPR-Cas Systems , Blood Coagulation Factors/biosynthesis , Blood Coagulation Factors/genetics , Fibrinogen/genetics , Gene Editing/methods , HEK293 Cells , Humans , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Transcriptional Activation
18.
Am J Surg ; 224(2): 694-697, 2022 08.
Article in English | MEDLINE | ID: mdl-35183350

ABSTRACT

BACKGROUND: Despite the fact that women comprise half of medical school graduates, women remain under-represented in General Surgery. We aimed to identify the trend in military general surgery applicants based on gender. METHODS: A retrospective review of the Medical Operational Data System (MODS) applicants from 2014 to 2019 was performed. Demographic data included age, gender, average board scores, applied and matched specialty. RESULTS: 204 students applied and 167 applicants matched into Army General Surgery programs from 2014 to 2019. The percentage of all students applying to General Surgery was statistically higher in females (13.4% vs 9.0%, p = 0.04), with females matching at a statistically higher rate (77% vs 57%, p = 0.02). Over the last 6 years, 55% of residents in training are men and 45% are women. CONCLUSION: Army General Surgery programs have increased the amount of women in training over the last six years. We believe that this will ultimately translate to more female surgeons contributing to military medicine.


Subject(s)
General Surgery , Internship and Residency , Military Personnel , Surgeons , Female , General Surgery/education , Humans , Male , Retrospective Studies , Surgeons/education
20.
J Surg Res ; 270: 369-375, 2022 02.
Article in English | MEDLINE | ID: mdl-34736129

ABSTRACT

BACKGROUND: Damage control resuscitation has become the standard of care in military and civilian trauma. Early identification of blood product requirements may aid in optimizing the clinical decision-making process while improving trauma related outcomes. This study aimed to assess and compare multiple machine learning models for predicting patients at highest risk for massive transfusion on the battlefield. METHODS: Supervised machine learning approaches using logistic regression, support vector machine, neural network, and random forest techniques were used to create predictive models for massive transfusion using standard prehospital and arrival data points from the Department of Defense Trauma Registry, 2008-2016. Seventy percent of the population was used for model development and performance was validated using the remaining 30%. Models were tested for accuracy and compared by standard performance statistics. RESULTS: A total of 22,158 patients (97% male, 58% penetrating injury, median age 25-29 y/o, average Injury Severity Score 9, with an overall mortality of 3%) were included in the analysis. Massive transfusion was required by 7.4% of patients. Overall accuracy was found to be above 90% in all models tested. Following cross validation and model training, the random forest model outperformed the alternatively tested models for precision, recall, and area under the curve. CONCLUSION: Machine learning techniques may allow for more optimal and rapid identification of combat trauma patients at highest risk for massive transfusion. These powerful approaches may uncover novel correlations and help improve triage, activation of massive transfusion resources, and trauma-related outcomes. Further research seeking to optimize and apply these algorithms to trauma-centered research should be pursued.


Subject(s)
Military Personnel , Wounds and Injuries , Adult , Blood Transfusion , Female , Humans , Machine Learning , Male , Retrospective Studies , Trauma Centers , Triage/methods , Wounds and Injuries/therapy
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