Extremity Hemorrhage Research Articles

Evaluation of Hemostatic Effectiveness in a Standard Swine Hemorrhage Model of Severe Bleeding: A Comparative Study of Chitosan Gauze and Kaolin Gauze

Hemorrhage remains a critical factor contributing to avoidable fatalities in combat scenarios and civilian emergencies. Significant advancements have been made in managing extremity hemorrhage through tourniquet application, although not all injuries can be effectively treated with this method. In the United States, the Committee on Tactical Combat Casualty Care (CoTCCC) has emphasized the importance of employing hemostatic dressings during initial trauma care as an alternative when tourniquet application is not feasible. Similar recommendations have been adopted globally, highlighting the pivotal role of topical hemostats in managing such critical situations. Among the recommended topical hemostats, hemostatic gauze, composed of biomaterials including chitosan and kaolin, has demonstrated superior efficacy in rapidly achieving hemostasis. The objective of this study was to evaluate the hemostatic efficacy of axiostat gauze (AG) in an extremity arterial hemorrhage model in swine and compare it with QuikClot Combat Gauze (QCG). The femoral artery was selected to create a model of severe arterial hemorrhage. This model is widely accepted as a standardized combat injury model by military laboratories, including those of the US Department of Defense. The findings indicate that AG has a superior safety profile, evidenced by the absence of particle release, and offers advantages in terms of faster hemostasis, reduced overall blood loss, and greater fluid absorbency compared to QCG. Although AG achieved quicker hemostasis, both AG and QCG ultimately provided effective eventual hemostasis in all animals, demonstrating comparable overall efficacy. In addition to its hemostatic performance, AG also possesses antimicrobial properties and is biocompatible. These attributes make AG a highly effective option for managing severe traumatic bleeding. Thus, AG can be recommended for use in both military and civilian pre-hospital settings as a strategic solution for critical bleeding situations.

Who needs a tourniquet? And who does not? Lessons learned from a review of tourniquet use in the Russo-Ukrainian war.

Extremity tourniquets have proven to be lifesaving in both civilian and military settings and should continue to be used by first responders for trauma patients with life-threatening extremity bleeding. This is especially true in combat scenarios in which both the casualty and the first responder may be confronted by the imminent threat of death from hostile fire as the extremity hemorrhage is being treated. Not every extremity wound, however, needs a tourniquet. One of the most important aspects of controlling life-threatening extremity bleeding with tourniquets is to recognize what magnitude of bleeding requires this intervention and what magnitude of bleeding does not. Multiple studies, both military and civilian, have shown that tourniquets are often applied when they are not medically indicated. Overuse of extremity tourniquets has not caused excess morbidity in either the recent conflicts in Iraq and Afghanistan or in the US urban civilian setting. In the presence of prolonged evacuation, however, applying a tourniquet when it is not medically indicated changes tourniquet application from being a lifesaving intervention to one that may cause an avoidable amputation and the development of an array of metabolic derangements and acute kidney injury collectively called prolonged tourniquet application syndrome. The recent literature was reviewed for papers that documented the complications of tourniquet use resulting from the prolonged casualty evacuation times being seen in the current Russo-Ukrainian war. The literature was also reviewed for the incidence of tourniquet application that was found to not be medically indicated, in both the US civilian setting and from Ukraine. Finally, an in-person meeting of the US/Ukraine Tourniquet Working Group was held in Warsaw, Poland, in December of 2023. Unnecessary loss of extremities and life-threatening episodes of prolonged tourniquet application syndrome are currently occurring in Ukrainian combat forces because of nonindicated tourniquet use combined with the prolonged evacuation time seen in the Russo-Ukrainian war. Specific numbers of the complications experienced as a result of tourniquet use by Ukrainian forces in the current conflict are treated as classified information and are not available, but multiple sources from the Ukrainian military medical personnel and from the US advisors providing medical assistance to Ukraine have all agreed that the problem is substantial. Unnecessary tourniquet morbidity might also occur in US forces in a variety of potential future combat scenarios in which evacuation to surgical care is delayed. Prehospital trauma training programs, including but not limited to tactical combat casualty care, place insufficient emphasis on the need to avoid leaving tourniquets in place when they are not medically indicated. This aspect of training should receive emphasis in future Tactical Combat Casualty Care (TCCC) and civilian first responder curriculum development. An interim ad hoc training solution on this topic is available at the websites noted in this articles. Additional training modalities may follow in the near future. Therapeutic/Care Management; Level V.

Renal Function and Survival are Reduced in a Polytrauma Acute Radiation Injury Rat Model with Extremity Trauma and Hemorrhage

The objective of this study was to evaluate whether the presence of radiation injury (RI) decreases survival in an established model of battlefield trauma and hemorrhage in rats. We hypothesized that the addition of radiation to our established traumatic hemorrhage model would increase mortality. Methods: On day zero (D0), male Sprague Dawley rats (n=6/group) received Buprenorphine SR prior to being anesthetized with isoflurane to perform catheterization of a carotid artery. Twenty-four hours later (day 1 or D1), rats were randomly assigned to 1 of 4 groups: 1- sham (no injury; no radiation); 2- RI only; 3- traumatic hemorrhage alone (ET+HEM); or 4- RI combined with traumatic hemorrhage (RI+ET+HEM). For RI and RI+ET+HEM groups, rats were anesthetized and placed inside a cabinet X-ray irradiator (MultiRad 350, Precision, CT) to receive a single sub-lethal X-ray dose of 5.5 Gy, delivered at 1 Gy/min, to induce acute radiation injury. For ET+HEM and RI+ET+HEM groups, under isoflurane, rat then received a unilateral extremity trauma injury. After 90 minutes, a conscious hemorrhage of 37% of the rat estimated blood volume was withdrawn. Rats were monitored for 14 days following injury or sham procedures and provided Buprenorphine SR as needed for pain. Rats remained un-resuscitated and renal function was assessed in vivo by glomerular filtration rate (GFR). GFR was measured with a probe non-invasively and securely strapped to the belly of the rat for about 2.5h. Samples for GFR were collected on D1, day 3 (D3), and day 15 (D15) (or terminal day) from the injury. Result: Sham rats had 100% survival at D15, while RI and ET+HEM rats both had 50% mortality. RI+ET+HEM rats, however, demonstrated 100% mortality by D15; differences in survival proportions were significant (P=0.005). Sham rats showed no significant decrease in GFR (1.0-1.2 ml/min/100g) from D1 to D15. Rats from RI group showed a slight decrease in GFR from D1 to D3 (1.2 to 0.9 ml/min/100g, respectively) at the D3 of measurement. By D15, GFR was 33% lower than D1 in RI group. ET+HEM group showed significant decline in GFR on D1 and D3. However, RI+ET+HEM group showed the most significant decline in GFR ( i.e., >50% lower than sham group on D1 and D3), with little to no improvement over time. Conclusion: We developed a new rodent model of RI+ET+HEM by combining high dose of X-ray irradiation with traumatic hemorrhage, which allows acute (hours) as well as chronic (days) observation. While RI or ET+HEM alone produced significant mortality, the combination of traumatic hemorrhage with RI increased mortality to 100% before D15. Radiation injury combined with extremity trauma and hemorrhage results in significant impairment of renal function. Extremity trauma and hemorrhage impaired renal function more than radiation injury alone. Disclaimer: The views expressed in this abstract are those of the author(s) and do not reflect the offcial policy or position of the U.S. Army Medical Department, Department of the Army, DoD, or the U.S. Government. Supported by Biomedical Advanced Research and Development Authority (BARDA). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Inflammatory Responses of the Remote Organs After Tourniquet-Induced Ischemia-Reperfusion in Mouse Hindlimb

Tourniquet use is the most effective tool for controlling life-threatening extremity hemorrhage before other treatments and for creating bloodless operating fields in surgical procedures. However, tourniquet-induced ischemia-reperfusion (IR) also causes skeletal muscle injury and associated secondary end-organ damage. Our previous studies have demonstrated that there are involvements of inflammatory cytokines in tourniquet-induced skeletal muscle IR injuries. The objective of this study is to investigate the inflammatory responses of end-organs after tourniquet-induced mouse hindlimb IR. We hypothesized that tourniquet use would result in an inflammatory response in the remote organs. The unilateral hindlimbs of mice were subjected to 3 hours of tourniquet application by placing a rubber band at the hip joint. Then the rubber bands were released for reperfusion over different periods of time (1, 3, 7, and 14 days). The mRNA levels of IL-1β and TNFα (two inflammatory cytokines) in the lungs, liver, kidneys, and heart were measured using real-time RT-PCR analysis. In the lungs, the levels of IL-1β and TNFα mRNA were significantly elevated at day 1 after tourniquet-induced IR, then decreased at days 3 and 7, and returned to a high level at day 14. In the liver, the levels of IL-1β and TNFα mRNA were increased at day 1 and remained at a high level until day 14. However, tourniquet-induced hindlimb IR did not change the levels of IL-1β or TNFα mRNA in the kidneys or heart during the whole period of tourniquet-induced IR. In conclusion, these results suggest that the inflammatory response to tourniquet-induced hindlimb IR is different among distant organs, which will help to develop therapeutic strategies for different end-organs after tourniquet-induced hindlimb IR. NIH/NIGMS 1R01GM145736 to Y-LL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A clinically-relevant mouse model that displays hemorrhage exacerbates tourniquet-induced acute kidney injury.

Hemorrhage is a leading cause of death in trauma. Tourniquets are effective at controlling extremity hemorrhage and have saved lives. However, tourniquets can cause ischemia reperfusion injury of limbs, leading to systemic inflammation and other adverse effects, which results in secondary damage to the kidney, lung, and liver. A clinically relevant animal model is critical to understanding the pathophysiology of this process and developing therapeutic interventions. Despite the importance of animal models, tourniquet-induced lower limb ischemia/reperfusion (TILLIR) models to date lack a hemorrhage component. We sought to develop a new TILLIR model that included hemorrhage and analyze the subsequent impact on kidney, lung and liver injuries. Four groups of mice were examined: group 1) control, group 2) hemorrhage, group 3) tourniquet application, and group 4) hemorrhage and tourniquet application. The hemorrhagic injury consisted of the removal of 15% of blood volume through the submandibular vein. The tourniquet injury consisted of orthodontic rubber bands applied to the inguinal area bilaterally for 80min. Mice were then placed in metabolic cages individually for 22h to collect urine. Hemorrhage alone did not significantly affect transcutaneous glomerular filtration rate (tGFR), blood urea nitrogen (BUN) or urinary kidney injury molecule-1 (KIM-1) levels. Without hemorrhage, TILLIR decreased tGFR by 46%, increased BUN by 162%, and increased KIM-1 by 27% (p < 0.05 for all). With hemorrhage, TILLIR decreased the tGFR by 72%, increased BUN by 395%, and increased urinary KIM-1 by 37% (p < 0.05 for all). These differences were statistically significant (p < 0.05). While hemorrhage had no significant effect on TILLIR-induced renal tubular degeneration and necrosis, it significantly increased TILLIR-induced lung total injury scores and congestion, and fatty liver. In conclusion, hemorrhage exacerbates TILLIR-induced acute kidney injury and structural damage in the lung and liver.

Transected popliteal artery via gunshot wound: A case report

Introduction: Popliteal artery transection is an uncommon injury but can be seen in traumas like gunshots, stabs, and complex fractures of the distal femur or proximal tibia. Although uncommon, these injuries carry the greatest risk of limb loss of any peripheral vascular injury. Timely hemostasis and repair is crucial to limb-salvage and overall survival, as lower extremity amputation is known to have very high mortality rates. We present a multiple gunshot wound patient who was found to have a completely transected popliteal artery injury and who underwent open surgical repair with interposition vein graft using the greater saphenous vein, ultimately resulting in two-vessel runoff and limb salvage. Case Report: A 30-year-old man with no known past medical history presented to the hospital via private vehicle after being shot multiple times just prior to arrival. Obvious injuries noted were two gunshot wounds to the left hand with hemorrhage, two gunshot wounds to the right thumb without hemorrhage, one gunshot wound to the left upper quadrant, one gunshot wound to the left flank, and one to the right lower extremity in the posterior distal thigh with massive hemorrhage. He was emergently taken to the operating room where exploration of the right popliteal artery and vein was performed which revealed a completely transected popliteal artery. The bullet was found to be lodged in the distal femur. The left great saphenous vein was then harvested in order to use it to repair the right popliteal artery with an interposition vein bypass. Intraoperative angiogram confirmed 2-vessel runoff. A four-compartment fasciotomy was performed prophylactically to avoid compartment syndrome. Postoperatively, the patient was extubated on post-op day 1. On post-op day 7, he was transferred out of the ICU and underwent split thickness skin grafting to the right lower extremity fasciotomy wounds. On post-op day 18, he was discharged home with a walker and the ability to move all extremities. He has now recovered full ambulatory function. Conclusion: Transection of popliteal artery should be considered in trauma patients with profuse lower extremity bleeding. In severe injuries and hemodynamically unstable patients, prompt hemostasis should be achieved and open surgical repair with an interposition vein graft should be considered for limb salvage.

A Review of75th Ranger Regiment Battle-Injured Fatalities Incurred During Combat Operations From 2001 to 2021.

The 75th Ranger Regiment is an elite U.S. military special operations unit that conducted over 20 years of sustained combat operations. The Regiment has a history of providing novel and cutting-edge prehospital trauma care, advancing and translating medical initiatives, and documenting and reporting casualty care performance improvement efforts. A retrospective case fatality rate (CFR) review, mortality review, and descriptive analysis of fatalities were conducted for battle-injured personnel assigned or attached to the 75th Ranger Regiment from 2001 to 2021 during combat operations primarily in Afghanistan and Iraq. Fatalities were evaluated for population characteristics, cause of death, mechanism of death, injury severity, injury survivability, and death preventability. A total of 813 battle injury casualties, including 62 fatalities, were incurred over 20 years and 1 month of continuous combat operations. The Regiment maintained a zero rate of prehospital preventable combat death. Additionally, no fatalities had a mechanism of death because of isolated extremity hemorrhage, tension pneumothorax, or airway obstruction. When comparing the CFR of the Regiment to the U.S. military population as a whole, the Regiment had a significantly greater reduction in the cumulative CFR as measured by the difference in average annual percentage change. Documentation and analysis of casualties and care, mortality and casualty reviews, and other performance improvement efforts can guide combatant commanders, medical directors, and fighting forces to reduce preventable combat deaths and the CFR. Early hemorrhage control, blood product resuscitation, and other lifesaving interventions should be established and maintained as a standard prehospital practice to mitigate fatalities with potentially survivable injuries.

Smart Tactical Application Tourniquet Versus Combat Application Tourniquet: Comparing Layperson Applications for Arterial Occlusion After a Video Demonstration.

Tourniquet efficacy for extremity hemorrhage is well established, although literature demonstrates variable first responder application efficacy. Several newer models, including the Smart Tactical Application Tourniquet (STAT, STAT Medical Devices, LLC, Freehold, New Jersey), offer alternatives to well-established devices like the Combat Application Tourniquet (CAT, C-A-T Resources, LLC, Rock Hill, South Carolina). Newer models are commercially sold without significant literature regarding efficacy or user feedback. We developed a pilot study to compare CAT and STAT applications for layperson hemorrhage control efficacy after a brief, standardized instructional video. This is a prospective randomized observational study that utilized layperson volunteers for the application of STAT or CAT. After a demographic survey, volunteers were randomized and watched the respective tourniquet instructional video, then applied the tourniquet to a HapMed hemorrhage simulator. The application was assessed for trial time, time to hemorrhage control, occlusion pressure, and total blood loss. Investigators also evaluated volunteers for proper application and received user feedback. Eighty-four total volunteers (42 CAT, 42 STAT) completed testing. Volunteers applied the CAT (50.0%, n = 21) with significantly greater rates of success than the STAT (0%, n = 0, p < 0.001).The CAT demonstrated significantly greater average occlusion pressure compared to the STAT (409.9 mm Hg vs. 116.5 mm Hg, p < 0.001).Similarly, CAT application resulted in significantly less average blood loss compared to the STAT (577.8 mL vs. 974.6 mL, p < 0.001). On the 5-point Likert scale, volunteers reported significantly higher benefits from video instruction and comfort with tourniquet application with the CAT over the STAT (4.7 vs. 4.0, p < 0.001, 4.0 vs. 2.4, p < 0.001). When performed by laypersons with minimal video instruction, the CAT was applied with significantly higher rates of success, higher mean occlusion pressures, reduced blood loss, and higher end-user ratings than the STAT.

Immediate Medical Care Rendered by U.S. Law Enforcement Officers After Officer-Involved Shootings – An Open-Access Public Domain Video Analysis

Introduction:After officer-involved shootings, rapid delivery of emergency medical care is critical but may be delayed due to scene safety concerns. The purpose of this study was to describe medical care rendered by law enforcement officers (LEO) after lethal force incidents.Method:Retrospective analysis of open-source video footage of officer-involved shootings (OIS) occurring between 2/15/2013 and 12/31/2020. Frequency and nature of care provided, time until LEO and emergency medical services (EMS) care, and mortality outcomes were evaluated. The study was deemed exempt by the Mayo Clinic Institutional Review Board.Results:342 videos were included in the final analysis. LEOs rendered care in 172 (50.3%) incidents. The average elapsed time from the time of injury to LEO-provided care was 155.8 + 198.8 seconds. Hemorrhage control was the most common intervention performed. An average of 214.2 seconds elapsed between LEO care and EMS arrival. No mortality difference was identified between LEO vs EMS care (p = 0.1631). Subjects with truncal wounds were more likely to die than those with extremity wounds (p &lt; 0.00001).Conclusion:LEO rendered medical care in half of all OIS incidents, initiating care on average 3.5 minutes prior to EMS arrival. Although no significant mortality difference was noted for LEO versus EMS care, this finding must be interpreted cautiously, as specific interventions, such as extremity hemorrhage control, may have impacted select patients. Future studies are needed to determine optimal LEO care for these patients.

Immediate Medical Care Rendered by US Law Enforcement Officers after Officer-Involved Shootings - An Open-Access Public Domain Video Analysis.

After officer-involved shootings (OIS), rapid delivery of emergency medical care is critical but may be delayed due to scene safety concerns. The purpose of this study was to describe medical care rendered by law enforcement officers (LEOs) after lethal force incidents. Retrospective analysis of open-source video footage of OIS occurring from February 15, 2013 through December 31, 2020. Frequency and nature of care provided, time until LEO and Emergency Medical Services (EMS) care, and mortality outcomes were evaluated. The study was deemed exempt by the Mayo Clinic Institutional Review Board. Three hundred forty-two (342) videos were included in the final analysis; LEOs rendered care in 172 (50.3%) incidents. Average elapsed time from time-of-injury (TOI) to LEO-provided care was 155.8 (SD = 198.8) seconds. Hemorrhage control was the most common intervention performed. An average of 214.2 seconds elapsed between LEO care and EMS arrival. No mortality difference was identified between LEO versus EMS care (P = .1631). Subjects with truncal wounds were more likely to die than those with extremity wounds (P < .00001). It was found that LEOs rendered medical care in one-half of all OIS incidents, initiating care on average 3.5 minutes prior to EMS arrival. Although no significant mortality difference was noted for LEO versus EMS care, this finding must be interpreted cautiously, as specific interventions, such as extremity hemorrhage control, may have impacted select patients. Future studies are needed to determine optimal LEO care for these patients.

Tourniquet-induced ischemia creates increased risk of organ dysfunction and mortality following delayed limb amputation

Tourniquets are critical for the control of traumatic extremity hemorrhage. In this study, we sought to determine, in a rodent blast-related extremity amputation model, the impact of prolonged tourniquet application and delayed limb amputation on survival, systemic inflammation, and remote end organ injury. Adult male Sprague Dawley rats were subjected to blast overpressure (120±7 kPa) and orthopedic extremity injury consisting femur fracture, one-minute soft tissue crush injury (20 psi), ± 180 min of tourniquet-induced hindlimb ischemia followed by delayed (60 min of reperfusion) hindlimb amputation (dHLA). All animals in the non-tourniquet group survived whereas 7/21 (33%) of the animals in the tourniquet group died within the first 72 h with no deaths observed between 72 and 168 h post-injury. Tourniquet induced ischemia-reperfusion injury (tIRI) likewise resulted in a more robust systemic inflammation (cytokines and chemokines) and concomitant remote pulmonary, renal, and hepatic dysfunction (BUN, CR, ALT. AST, IRI/inflammation-mediated genes). These results indicate prolonged tourniquet application and dHLA increases risk of complications from tIRI, leading to greater risk of local and systemic complications including organ dysfunction or death. We thus need enhanced strategies to mitigate the systemic effects of tIRI, particularly in the military prolonged field care (PFC) setting. Furthermore, future work is needed to extend the window within which tourniquet deflation to assess limb viability remains feasible, as well as new, limb-specific or systemic point of care tests to better assess the risks of tourniquet deflation with limb preservation in order to optimize patient care and save both limb and life.

Efficacy of the Military Tactical Emergency Tourniquet for Lower Extremity Arterial Occlusion Compared with the Combat Application Tourniquet: A Randomized Crossover Study.

Extremity bleeding and subsequent hemorrhagic shock is one of the main causes of preventable battlefield death, leading to mass-fielding of modern tourniquets, such as the Combat Application Tourniquet (CAT; Composite Resources). Numerous look-alike tourniquets, such as the Military Tactical Emergency Tourniquet (MTET; SZCTKlink), flood commercial markets, offering visually near-identical tourniquets for drastically reduced prices. We examined the performance of the MTET compared with that of the CAT. We undertook a randomized crossover trial to observe self-applied tourniquets to the lower extremity by combat medics, comparing the CAT to the MTET in application time and success rates, proven by loss of distal pulse assessed by Doppler ultrasound in <1 minute. All 50 participants (100%) successfully applied the CAT versus 40 participants (80%) using the MTET (p = .0001). Median application time for the CAT (29.03 seconds; range, 18.63 to 59.50 seconds) was significantly less than those of successful MTET applications (35.27 seconds; range, 17.00 to 58.90 seconds) or failed MTET applications (72.26 seconds; range, 62.84 to 83.96 seconds) (p = .0012). Of 10 MTET failures, three (30%) were from application time >1 minute and seven (70%) from tourniquet mechanical failure. The MTET performed worse than the CAT did in all observed areas. Despite identical appearance, look-alike tourniquets should not be assumed to be equivalent in quality or functionality to robustly tested tourniquets.

Systematic review to evaluate algorithms for REBOA use in trauma and identify a consensus for patient selection

BackgroundPatient selection for resuscitative endovascular balloon occlusion of the aorta (REBOA) has evolved during the last decade. A recent multicenter collaboration to implement the newest generation REBOA balloon catheter identified...

Molecular characterization of recombinant premembrane protein of dengue virus serotype-2 for development of diagnostic assay.

Dengue is an acute arboviral infection common in tropical and subtropical countries. Dengue has been highlighted as a public health concern in the last five decades, affecting almost 50% of the population in developing nations. Dengue infection results in a complex symptomatic disease that ranges from headache, fever, and skin rash to extreme hemorrhage fever and liver dysfunction. The diagnosis of the disease is essential for effective treatment. The early onset of the infection can be detected through viral structural peptides that act as markers for detection, including Pre-Membrane (Pre-M) protein. In the currently proposed research, the structural gene obtained from local isolates was targeted for studies. For this purpose, recombinant structural protein Pre-M was amplified, cloned, and expressed in the bacterial expression system. The expression of the structural protein (Pre-M) was scrutinized by Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and validated by western blot and dot blot, and afterwards, the antigen was purified. The purified Pre-M protein carries the potential for the development of in-house diagnostic assay as well as for vaccine production. This study aimed to develop a highly specific, sensitive, and cost-effective in-house enzyme-linked immunoassay (ELISA) for the detection of antibodies of Pakistani most prevalent dengue virus serotype 2 (DENV-2). The success of this research would also pave the way toward developing novel vaccines for the future prevention of dengue infection.

High Intensity Focus Ultrasound Stimulation of Spleen Reduces Traumatic Bleeding in Mice

Introduction: Uncontrolled hemorrhage is the most common preventable cause of traumatic death. Direct pressure or tourniquets limit extremity bleeding, but non-compressible hemorrhage requires surgical control. Systemic hemostatic therapies are limited. In preclinical models of hemorrhage, electrical vagus nerve stimulation (VNS) accelerates thrombosis and decreases traumatic hemorrhage in a spleen-dependent manner. Here, we demonstrate that non-invasive high intensity focused ultrasound (HIFU) stimulation targeting the spleen significantly reduces bleeding in a murine tail transection model. Methods: Adult male C57BL/6J mice were anesthetized (ketamine/xylazine), placed in the right lateral decubitus position, and shaved after identifying the spleen by anatomical markers and palpation. The ultrasound probe was directed at the splenic hilum, followed by 1 min stimulation (1.1 MHz, 200 mV/pulse, 150 burst cycles, 500 μs burst period), a 30 s rest, and 1 min stimulation for a 5 min total stimulation. Animal tails were warmed in water (37°C, 5 min), transected 2 mm from the tip, and bled into water until hemorrhage stops for a minimum of 10 s to record the duration of bleeding (bleeding time). Results: Compared with sham stimulation, HIFU significantly reduces bleeding time after tail transection (Sham = 110.5 ± 7.7 s vs HIFU = 72.9 ± 6.6 s, Mean ± SEM, n = 10/group, p < 0.01 (two-tailed t-test). Conclusion: These data demonstrate that HIFU stimulation of the spleen provides a novel method to reduce traumatic hemorrhage. HIFU warrants additional study in traumatic and surgical bleeding, and as a treatment for bleeding disorders.

Comparison Of Non-clinical Tourniquet Research for Appliance Superiority &amp; Tolerance (CONTRAST)

BACKGROUND: Tourniquets are effective tools to manage life-threatening extremity hemorrhage. Commercial devices are recommended over improvised ones; however, mass casualty incidents and austere environments may prevent access to commercial devices. The aim of this review is to systematically search and meta-analyze commercial and improvised tourniquets: arterial occlusion, application speed, and patient tolerance. METHODS: We searched MEDLINE, Embase, CINAHL, Cochrane Library, SPORTDiscus, and ProQuest Dissertations &amp; Theses Global using controlled terms; without date limits. Manikin, animal, and operative studies were excluded. Tourniquet devices were pooled by design and compared. Data regarding provider training and experience, recipient anthropometrics, application site, ease of application, speed, tolerance, and device efficacy were examined. RESULTS: 5169 studies were screened. The 36 included studies were prospective trials on healthy volunteers and published between 2000 and 2021. There were 8205 unique tourniquet applications to 1921 subjects using 23 unique commercial and improvised devices. Median sample size of included studies was 20 (IQR 26) participants, ranging from 1 to 773 participants; and 102 (IQR=152) applications ranging from 20 individual applications to 1546 unique applications. The most commonly assessed outcomes were: effectiveness (n=30), pain (n=18), speed of application (n=13), and amount of mechanical advantage (ex. Windlass turns) required (n=13). Male participants outnumbered females 1,414 to 169, mean age ranged from 21 to 45 years of age. Devices were pooled into 5 categories according to mechanical advantage mechanism: elastic, friction, mechanical, pneumatic, and windlass. Initial hemostasis was achieved in 95% of upper extremity placements (CI=0.89-0.98, p= 0.02), and 88% of mid-thigh applications (CI=0.78-0.94, p&gt;0.01), in both groups pneumatic and mechanical tourniquet devices had the highest rates of success, with friction and elastic devices having the lowest rates of success. Meta-analysis showed that mechanical and pneumatic advantage systems had superior rates of hemostasis, ease of use, and pain tolerance scores. Due to study heterogeneity, we could not determine which devices were the fastest to apply. The overall risk of bias assessment for included studies found the certainty of studies ranged from moderate to critical. CONCLUSION: In pre-clinical studies mechanical and pneumatic advantage systems appear to be the superior tourniquet design. Due to the low certainty of evidence and non-randomizable nature of traumatic injury, pre-clinical tourniquet devices will likely continue to be tested on well volunteers. Adoption of a minimum data set, agreed upon definitions for testable metrics, and a standardized experimental design could improve the comparability and quality of future tourniquet device studies.

Application of Hemostatic Tourniquet on Wounded Extremities in Modern "Trench" Warfare: The View of a Vascular Surgeon.

Blood vessel injuries in modern military conflicts account for 12% of all wounds (1), and 50%-95% of these involve arterial damage in extremities (3, 5). Furthermore, 10%-15% of all deaths on the battlefield occur due to extremity hemorrhage (2). Therefore, tourniquets and compression dressings continue to be the main methods of controlling extremity hemorrhage (4). The article analyzes the use of hemostatic tourniquets on wounded extremities for personnel that were provided second-level medical care by a Forward Surgical Team (FST) of one of the field hospitals of the Armed Forces of Ukraine.In these clinical cases, care was provided at the FST base in one of the district hospitals and during visits to civilian frontline hospitals by a vascular surgeon. This FST provided medical care to all severely and moderately injured or wounded in the area.The analysis included both military and civilians delivered with hemostatic tourniquets on their extremities. Assistance was provided to 69 wounded or injured, including 5 civilians. In all, 102 tourniquets were applied on 95 extremities. Tourniquets were applied on all 95 (100%) extremities including 21 (22.1%) upper extremities and 74 (77.9%) lower extremities. In 5 cases, tourniquets were applied on 3 extremities, in 16 cases on 2 extremities, and in 48 cases on 1 extremity. Combat Application Tourniquets (CAT) were used in 81 (85.3%) cases, Esmarch type in 10 (10.5%) cases, and improvised tourniquets in 4 (4.2%) cases. Duration of tourniquet application was less than 1 hour in 27 cases, 1-2 hours in 18 cases, 2-3 hours in 15 cases, and over 3 hours in 9 cases.The level of primary blood loss at the time of admission was categorized as <1 L in 44 (63.7%) cases, 1.0-1.5 L in 11 (11.5%) cases, 1.5-2.0 L in 7 (7.2%) cases, 2.0-2.5 L in 3 (3.1%) cases, and >2.5 L in 4 (4.2%) cases. Main arteries were damaged in 14 extremities in 12 (17.4%) wounded. Main veins were damaged in 4 (5.8%) cases without the involvement of the main arteries. Damage to the branches of arteries and veins was seen in 53 (76.8%) of the wounded. Surgical procedures performed included main artery reconstruction in 6, ligation of main arteries in 2, main vein ligation in 4, primary amputations of extremities in 9, and surgical debridement with ligation of arterial and/or venous branches in 37 cases. Reasons for excessive blood loss (>1.0 L) included delayed tourniquet application in 8 cases, inadequate tourniquet application in 12 cases, and bleeding secondary to injuries of the chest/abdominal cavity or head in 5 cases. (1) Tourniquet application was appropriate in 24.6% of the wounded with tourniquets.(2) The success of hemostatic tourniquet use is dependent upon the experience of staff rather than the type of tourniquet used.(3) In patients with significant blood loss, the duration of ischemia should be calculated from the time of injury and not from the time tourniquet was applied.(4) During the reconstruction of the main arteries in extremities after the prolonged use of the tourniquet, a longer than usual anastomosis line is advised.(5) Injuries to upper extremities will be more common during active combat, compared to positional warfare in fortified positions.

Diabetic Retinopathy: An Overview on Mechanisms, Pathophysiology and Pharmacotherapy

Diabetes mellitus is one of the most frequently occurring metabolic disorders (DMs), impairing healthy life around the globe, with mild-to-severe secondary complications. DM is associated with secondary complications, including diabetic retinopathy (DR), which damages the retina and can lead to vision loss. Diabetic patients often suffer from extreme retinal capillary aneurysms, hemorrhage, and edema, which is likely to lead to non-proliferative or proliferative diabetic retinopathy (NPDR or PDR) and diabetic macular edema (DME). Several epidemiological studies have illustrated that the occurrence of DR can vary by age of diabetes onset, diabetes type, and ethnicity. Although DR is very well-known, the complexity of its etiology and diagnosis makes therapeutic intervention difficult and challenging. We have reviewed different pathological aspects of diabetic retinopathy and its underlying mechanism of occurrence. In this review, we aim to provide an in-depth understanding and illustration of the progression of diabetic retinopathy, its pathophysiology, epidemiology, and prospective therapeutic targets.

AAST multicenter prospective analysis of prehospital tourniquet use for extremity trauma.

Tourniquet use for extremity hemorrhage control has seen a recent increase in civilian usage. Previous retrospective studies demonstrated that tourniquets improve outcomes for major extremity trauma (MET). No prospective study has been conducted to date. The objective of this study was to evaluate outcomes in MET patients with prehospital tourniquet use. We hypothesized that prehospital tourniquet use in MET decreases the incidence of patients arriving to the trauma center in shock. Data were collected prospectively for adult patients with MET at 26 Level I and 3 Level II trauma centers from 2015 to 2020. Limbs with tourniquets applied in the prehospital setting were included in the tourniquet group and limbs without prehospital tourniquets were enrolled in the control group. A total of 1,392 injured limbs were enrolled with 1,130 tourniquets, including 962 prehospital tourniquets. The control group consisted of 262 limbs without prehospital tourniquets and 88 with tourniquets placed upon hospital arrival. Prehospital improvised tourniquets were placed in 42 patients. Tourniquets effectively controlled bleeding in 87.7% of limbs. Tourniquet and control groups were similarly matched for demographics, Injury Severity Score, and prehospital vital signs (p > 0.05). Despite higher limb injury severity, patients in the tourniquet group were less likely to arrive in shock compared with the control group (13.0% vs. 17.4%, p = 0.04). The incidence of limb complications was not significantly higher in the tourniquet group (p > 0.05). This study is the first prospective analysis of prehospital tourniquet use for civilian extremity trauma. Prehospital tourniquet application was associated with decreased incidence of arrival in shock without increasing limb complications. We found widespread tourniquet use, high effectiveness, and a low number of improvised tourniquets. This study provides further evidence that tourniquets are being widely and safely adopted to improve outcomes in civilians with MET. Therapeutic/Care Management; Level IV.

Supervisory Algorithm for Autonomous Hemodynamic Management Systems.

Future military conflicts will require new solutions to manage combat casualties. The use of automated medical systems can potentially address this need by streamlining and augmenting the delivery of medical care in both emergency and combat trauma environments. However, in many situations, these systems may need to operate in conjunction with other autonomous and semi-autonomous devices. Management of complex patients may require multiple automated systems operating simultaneously and potentially competing with each other. Supervisory controllers capable of harmonizing multiple closed-loop systems are thus essential before multiple automated medical systems can be deployed in managing complex medical situations. The objective for this study was to develop a Supervisory Algorithm for Casualty Management (SACM) that manages decisions and interplay between two automated systems designed for management of hemorrhage control and resuscitation: an automatic extremity tourniquet system and an adaptive resuscitation controller. SACM monitors the required physiological inputs for both systems and synchronizes each respective system as needed. We present a series of trauma experiments carried out in a physiologically relevant benchtop circulatory system in which SACM must recognize extremity or internal hemorrhage, activate the corresponding algorithm to apply a tourniquet, and then resuscitate back to the target pressure setpoint. SACM continues monitoring after the initial stabilization so that additional medical changes can be quickly identified and addressed, essential to extending automation algorithms past initial trauma resuscitation into extended monitoring. Overall, SACM is an important step in transitioning automated medical systems into emergency and combat trauma situations. Future work will address further interplay between these systems and integrate additional medical systems.