A thermal cross-linking approach to developing a reinforced elastic chitosan cryogel for hemostatic management of heavy bleeding.

Uncontrolled hemorrhage stands as the primary cause of potentially preventable deaths following traumatic injuries in both civilian and military populations. Addressing this critical medical need requires the development of a hemostatic material with rapid hemostatic performance and biosafety. This work describes the engineering of a chitosan-based cryogel construct using thermo-assisted cross-linking with α-ketoglutaric acid after freeze-drying. The resulting cryogel exhibited a highly interconnected macro-porous structure with low thermal conductivity, exceptional mechanical properties, and great fluid absorption capacity. Notably, assessments using rabbit whole blood in vitro, as well as rat liver volume defect and femoral artery injury models simulating severe bleeding, showed the remarkable hemostatic performance of the chitosan cryogel. Among the cryogel variants with different chitosan molecular weights, the 150 kDa one demonstrated superior hemostatic efficacy, reducing blood loss and hemostasis time by approximately 73 % and 63 % in the hepatic model, and by around 60 % and 68 %, in the femoral artery model. Additionally, comprehensive in vitro and in vivo evaluations underscored the good biocompatibility of the chitosan cryogel. Taken together, these results strongly indicate that the designed chitosan cryogel configuration holds significant potential as a safe and rapid hemostatic material for managing severe hemorrhage.

Formation of a Pseudoaneurysm after a .22 Caliber Bullet Embolized to the Left Femoral Artery: A Case Report.

Bullet embolization is a rare and potentially life-threatening complication of gunshot wounds, particularly in lowpowered and small-caliber bullets. When these small bullets enter a large elastic vessel, they have the potential to leave a small entrance hole that can form a traumatic pseudoaneurysm. These pseudoaneurysms, which may be life-protecting at first, may rupture and lead to exsanguination if not found. We report an interesting case of an 18-year-old male gunshot victim where a bullet formed an aortic pseudoaneurysm and subsequently embolized and present a review of the literature regarding bullet embolization and traumatic pseudoaneurysms.

Delayed femoral artery injury caused by heterotopic ossification: a rare case report and review of the literature.

BACKGROUND: Arterial injury caused by heterotopic ossification (HO) following fractures is rarely reported, yet it can have catastrophic consequences. This case report presents a unique instance of femoral artery injury and hematoma organization, occurring a decade after intramedullary nail fixation for a femoral shaft fracture complicated by HO. CASE PRESENTATION: A 56-year-old male presented with right femoral artery injury and organized hematoma, a decade after suffering bilateral femoral shaft fractures with mild head injury in a traffic accident. He had received intramedullary nailing for the right femoral shaft fracture and plate fixation for the left side in a local hospital. Physical examination revealed two firm, palpable masses with clear boundaries, limited mobility, and no tenderness. Peripheral arterial pulses were intact. Radiography demonstrated satisfactory fracture healing, while a continuous high-density shadow was evident along the inner and posterior aspect of the right thigh. Computed tomography angiography identified a large mixed-density mass (16.8 × 14.8 × 20.7 cm) on the right thigh's medial side, featuring central calcification and multiple internal calcifications. The right deep femoral artery coursed within this mass, with a smaller lesion noted on the posterior thigh. Surgical consultation with a vascular surgeon led to planned intervention. The smaller mass was completely excised, but the larger one partially, as it encased the femoral artery. The inability to remove all HO was due to excessive bleeding. Postoperatively, the patient experienced no complications, and one-year follow-up revealed a favorable recovery with restoration of full right lower limb mobility. CONCLUSION: This case underscores the potential gravity of vascular injury associated with heterotopic ossification. Surgeons should remain vigilant regarding the risk of vascular injury during HO excision.

Biomimetic and Wound Microenvironment-Modulating PEGylated Glycopolypeptide Hydrogels for Arterial Massive Hemorrhage and Wound Prohealing.

Despite great progress in the hydrogel hemostats and dressings, they generally lack resistant vascular bursting pressure and intrinsic bioactivity to meet arterial massive hemorrhage and proheal wounds. To address the problems, we design a kind of biomimetic and wound microenvironment-modulating PEGylated glycopolypeptide hydrogels that can be easily injected and gelled in ∼10 s. Those glycopolypeptide hydrogels have suitable tissue adhesion of ∼20 kPa, high resistant bursting pressure of ∼150 mmHg, large microporosity of ∼15 µm, and excellent biocompatibility with ∼1% hemolysis ratio and negligible inflammation. They performed better hemostasis in rat liver and rat and rabbit femoral artery bleeding models than Fibrin glue, Gauze, and other hydrogels, achieving fast arterial hemostasis of <20 s and lower blood loss of 5-13%. As confirmed by in vivo wound healing, immunofluorescent imaging, and immunohistochemical and histological analyses, the mannose-modified hydrogels could highly boost the polarization of anti-inflammatory M2 phenotype and downregulate pro-inflammatory tumor necrosis factor-α to relieve inflammation, achieving complete full-thickness healing with thick dermis, dense hair follicles, and 90% collagen deposition. Importantly, this study provides a versatile strategy to construct biomimetic glycopolypeptide hydrogels that can not only resist vascular bursting pressure for arterial massive hemorrhage but also modulate inflammatory microenvironment for wound prohealing.

Suppression of neointimal hyperplasia induced by arteriovenous anastomosis and balloon injury in rats by multimeric tumor necrosis factor-related apoptosis-inducing ligand.

Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on anastomosis of the carotid artery and jugular vein- or balloon-induced NH.

Elevated plasma levels of factor VIII enhance arterial thrombus formation on erosive smooth muscle cell-rich neointima but not normal intima in rabbits.

BACKGROUND: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. AIMS: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. METHODS AND RESULTS: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5'-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. CONCLUSIONS: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.

Impact of Tissue Damage and Hemodynamics on Restenosis Following Percutaneous Transluminal Angioplasty: A Patient-Specific Multiscale Model.

Multiscale agent-based modeling frameworks have recently emerged as promising mechanobiological models to capture the interplay between biomechanical forces, cellular behavior, and molecular pathways underlying restenosis following percutaneous transluminal angioplasty (PTA). However, their applications are mainly limited to idealized scenarios. Herein, a multiscale agent-based modeling framework for investigating restenosis following PTA in a patient-specific superficial femoral artery (SFA) is proposed. The framework replicates the 2-month arterial wall remodeling in response to the PTA-induced injury and altered hemodynamics, by combining three modules: (i) the PTA module, consisting in a finite element structural mechanics simulation of PTA, featuring anisotropic hyperelastic material models coupled with a damage formulation for fibrous soft tissue and the element deletion strategy, providing the arterial wall damage and post-intervention configuration, (ii) the hemodynamics module, quantifying the post-intervention hemodynamics through computational fluid dynamics simulations, and (iii) the tissue remodeling module, based on an agent-based model of cellular dynamics. Two scenarios were explored, considering balloon expansion diameters of 5.2 and 6.2 mm. The framework captured PTA-induced arterial tissue lacerations and the post-PTA arterial wall remodeling. This remodeling process involved rapid cellular migration to the PTA-damaged regions, exacerbated cell proliferation and extracellular matrix production, resulting in lumen area reduction up to 1-month follow-up. After this initial reduction, the growth stabilized, due to the resolution of the inflammatory state and changes in hemodynamics. The similarity of the obtained results to clinical observations in treated SFAs suggests the potential of the framework for capturing patient-specific mechanobiological events occurring after PTA intervention.

Profunda Femoris Pseudoaneurysm and Fatal Hemorrhage 2 Weeks After Modified Girdlestone Resection Arthroplasty: A Case Report.

CASE: A 62-year-old nonambulatory female patient presented with wound dehiscence and purulent bloody drainage 2 weeks after modified Girdlestone resection arthroplasty for subtrochanteric femur fracture. On developing an enlarging thigh hematoma and hemodynamic instability, the patient was taken to the vascular suite where a profunda femoris artery pseudoaneurysm was identified and ligated by the vascular surgery team. The proximal free edge of the resected femur was determined to be the likely cause of arterial injury. Two days later, the patient was taken by the orthopaedic surgery team for debridement and revision resection arthroplasty, but she ultimately decompensated and died. CONCLUSION: We believe this to be the first reported case of this serious complication of the Girdlestone procedure. We hope this case helps bring awareness to the complication and aids in early detection and prompt treatment of femoral artery complications.

32-year-old Traumatic Arteriovenous Fistula Presenting With Leg Ulcer and High-output Heart Failure.

Traumatic arteriovenous fistula (AVF) is not a common disorder, and dermatological signs and heart failure caused by AVF are rarely reported. We present the case of a 55-year-old woman who was referred for congestive heart failure symptoms. Echocardiography revealed preserved left ventricular ejection fraction. Due to edema of the right leg with a long-standing leg ulcer and palpable femoral thrill, duplex ultrasonography was performed. It showed an AVF between the right superficial femoral artery (SFA) and the right femoral vein (FV). The patient recalled a 32-year-old gunshot injury that was not medically treated. After the diagnosis of AVF she was referred to a surgeon for an AVF ligation, with subsequent resolution of her symptoms. The differential diagnosis of leg ulcer with leg edema should include the possibility of AVF as a cause.

A modified chain-based sponge dressing controls junctional hemorrhage in the tactical combat casualty care simulation of pigs.

BACKGROUND: Hemorrhage has always been the focus of battlefield and pre-hospitalization treatment. With the increasing fatality rates associated with junctional bleeding, treatment of bleeding at junctional sites has gradually gained attention in battlefield trauma emergency care. We designed a modified chain-based sponge dressing with a medical polyvinyl alcohol sponge that can be used to treat junctional hemorrhage and tested its hemostatic efficacy and biocompatibility. METHODS: Twenty adult Bama miniature pigs were randomly divided into the modified chain-based sponge dressing (MCSD) and standard gauze (SG) groups. The right femoral artery of the pigs was shot at after anesthesia. The Bama miniature pigs were moved to the safety zone immediately to assess the condition according to the MARCH strategy, which evaluates massive hemorrhaging, airway obstruction, respiratory status, circulatory status, head injury & hypothermia. Hemoglobin and coagulation status were checked during the experiment.Among the pigs in which the inguinal hemorrhagic model based on bullet penetrating wounds was successfully established, those in the MCSD group received a disinfected MCSD for hemostasis, while those in the SG group received standard gauze in an imbricate manner to pack the bullet exit and entrance wounds to stop bleeding until the wound was filled, followed by compression for 3 min at sufficient pressure. CT scanning, transmission electron microscopy, and HE staining were conducted after experiment. RESULTS: The MCSD group showed lower hemostasis time and blood loss than the gauze group. The MCSD group also showed a higher success rate of treatment,more stable vital signs and hemoglobin level. The CT scanning results showed tighter packing without large gaps in the MCSD group. The histopathological assessments and the transmission electron microscopy and HE staining findings indicated good biocompatibility of the polyvinyl alcohol sponge. CONCLUSION: The MCSD met the battlefield's requirements of speedy hemostasis and biosafety for junctional hemorrhage in Bama miniature pigs. Moreover, in comparison with the conventional approach for hemostasis, it showed more stable performance for deep wound hemostasis. These findings provide the theoretical and experimental basis for the application of MCSD in the treatment of hemorrhage in the battlefield in the future.

Novel cross-linked polysaccharide-polyelectrolyte hemostatic foam improves survival compared to CombatGauze in swine femoral artery hemorrhage model.

BACKGROUND: Uncontrolled hemorrhage is the leading cause of preventable death in combat and civilian trauma. Efficacious hemostatic agents in junctional hemorrhage can quell blood loss and improve survival. We hypothesized that a novel hemostatic foam of starch and chitosan would improve hemostasis, and thereby increase survival in a swine femoral artery hemorrhage model when compared with CombatGauze (CG). METHODS: A novel hemostatic foam of starch and chitosan was created and modified during the study period. Thirty pigs (four excluded) were assigned to treatment using either foam version 1 (FV1, n = 9) or 2 (FV2, n = 8), or (n = 9) in a standard swine femoral artery hemorrhage model. Animals were observed for 150 minutes. Outcomes assessed included hemostasis, survival, posttreatment blood loss, IV fluid volume, and hemodynamic and laboratory trends. RESULTS: Hemostasis prior to 150 minutes was similar with 44.4%, 77.8%, and 50% of swine treated with CG, FV1 and FV2, respectively (Kaplan-Meyer and log-rank test [KM-LR] p > 0.05). Survival to 150 minutes was improved in swine treated with FV1 (100%) compared with CG (55.6%) (KM-LR p = 0.02). Survival was similar between FV1 and FV2 (75%) (KM-LR p > 0.05), and between CG and FV2 (KM-LR p > 0.05). Using mixed model for longitudinal data, mean arterial pressure decreased significantly in CG- and FV2-treated swine, while there was no significant change in mean arterial pressure in FV1-treated swine. Trends in lactic acid, hematocrit, platelets, INR, and thrombelastography were more favorable for FV1 compared with CG. CONCLUSION: In this preclinical study of junctional hemorrhage, survival was improved in swine treated with version 1 of a novel chitosan/starch foam compared with CG. Trends in hemodynamics and laboratory data were also more favorable in the FV1-treated swine. This novel hemostatic foam may be an effective alternative to current hemostatic agents.

Testing and Evaluation of a Novel Hemostatic Matrix in a Swine Junctional Hemorrhage Model.

INTRODUCTION: In an ongoing effort to improve survival and reduce blood loss from hemorrhagic injuries on the battlefield, new hemostatic dressings continue to be developed. This study aimed to determine the efficacy of a novel silicon dioxide-based hemostatic matrix (HM) and compare it with the current military standard Quikclot Combat Gauze (QCG) utilizing a lethal femoral artery injury model. MATERIALS AND METHODS: The femoral arteries of 20 anesthetized swine were isolated, and an arteriotomy was performed. After a 45 s free bleed, the wound was treated with either HM or QCG (n = 10 per group). Following a 60-min observation period, ipsilateral leg manipulations and angiography were performed. Animal survival, hemostasis, blood loss, exothermic reaction, and femoral artery patency were analyzed. RESULTS: Despite a volumetric size discrepancy between the two products tested, the survival rate was similar between the two groups (80% HM, 90% QCG, n = 10, P = 0.588). Immediate hemostasis was obtained in 50% of HM animals and 40% of QCG animals. There was no difference in total blood loss recorded between the two groups (P = 0.472). Femoral artery patency rates following ipsilateral leg manipulations were similar between the two groups (50% HM, 33% QCG, P = 0.637), with no contrast extravasation in HM-treated wounds (0% HM, 33% QCG, P = 0.206). There was no significant difference in either pretreatment or posttreatment laboratory values, and there were no exothermic reactions in either group. CONCLUSIONS: The SiOxMed HM demonstrated comparable hemostatic efficacy to QCG. The tested form of HM may be appropriate for surgical or topical hemostasis applications, and with further product development, it could be used for battlefield trauma implementation.

Lower extremity pseudoaneurysms and their interventional radiological management: a pictorial review.

Lower extremity pseudoaneurysms (PsAs) are mostly developed after traumatic or iatrogenic injury to the arteries. Unless treated, they can be complicated by adjacent mass effects, distal embolism, secondary infection, and rupture. Imaging helps in the diagnosis and planning of therapeutic intervention. Ultrasonography (USG) is often diagnostic, while CT angiography aids in vascular mapping required for intervention. Image-guided therapy offers to manage these pseudoaneurysms in a minimally invasive approach, obviating the need for surgery. A smaller, superficial, and narrow-necked PsA can easily be managed with local USG-guided compression or thrombin injection. When the percutaneous approach is not a feasible option, PsA from expendable arteries can also be managed with coiling or glue injection. Wide-necked PsA from an unexpendable artery necessitates stent graft placement, although coiling of the neck may be a viable and cheaper alternative for a long- and narrow-necked PsA. Presently, vascular closure devices are also used to seal a small arterial rent through a direct percutaneous approach. This pictorial review entails various techniques to deal with lower extremity pseudoaneurysms. An idea about the various intervention radiological approaches will help in choosing appropriate methods to tackle lower extremity pseudoaneurysms.

The effectiveness of the manual pressure points technique for hemorrhage control-The 2022 THOR pre-conference meeting experience.

INTRODUCTION: Limb and junctional hemorrhage are leading causes of potentially preventable death among trauma casualties. Hemorrhage control for these regions could be achieved by direct or indirect pressure. The manual pressure points (MPP) involves applying manual pressure on the arterial supply to occlude distal blood flow without the need for specialized equipment. STUDY DESIGN AND METHODS: Prospective, non-randomized, human volunteer, controlled environment study involving 38 healthy military caregivers, with 26 participants attending a short instructional session. During a medical exercise, participants were requested to apply pressure on the supraclavicular and femoral points aiming to stop regional blood flow, measured by distal pulse palpation. The measures recorded included achievement of distal pulse cessation, success in achieving cessation for a full minute, and subjects' pain scores reported after each attempt. RESULTS: All participants succeeded in achieving distal pulse cessation for both the supraclavicular and femoral points for a full minute. The median time to initial success was 3.0 (interquartile range 2.0-5.0) seconds in the supraclavicular point and 4.5 (interquartile range 3.0-6.0) seconds in the femoral point. Pain scores ranging between 0 and 3 were reported by most subjects during supraclavicular (68.4%) and femoral occlusion (84.2%). CONCLUSION: The MPP technique was highly effective in occluding distal palpable pulses in healthy volunteers when applied to the supraclavicular and femoral arteries. Brief instruction on the technique can potentially improve the chances of achieving hemorrhage control within 5 s. Further research is required to determine efficacy among different populations and providers with varying experience levels.

A novel sodium polyacrylate-based stasis dressing to treat lethal hemorrhage in a penetrating trauma swine model.

BACKGROUND: Control of massive hemorrhage from penetrating wound sites is difficult in both combat and civilian settings. A new hemostatic dressing, sodium polyacrylate (PAAs)-based bag (PB), based on PAAs is designed for the first aid of massive penetrating hemorrhage. This study aimed to investigate the efficacy of PB in a penetrating trauma model in swine. METHODS: A complex groin penetrating injury was produced in swine by completely excising the femoral vessels and surrounding muscles. After 15-second free bleeding, 18 healthy Guizhou female swine were administered PB (n = 6), CELOX-A (n = 6; Medtrade Products, Crewe, United Kingdom), or standard gauze (n = 6) for hemostatic intervention, followed by 3-minute compression if the bleeding persisted, with subsequent observation continuing for 1 hour. The primary outcomes included initial hemostasis, the incidence of applying manual pressure, and application time. RESULTS: Sodium polyacrylate could rapidly absorb the liquid to expand, crosslink with a large number of red blood cells, induce cellular morphological alteration, and promote blood coagulation. Sodium polyacrylate-based bag and CELOX-A initiated and sustained hemostasis for 60 minutes, whereas 0% of the standard gauze achieved initial hemostasis. Maximum number of manual compressions were applied in standard gauze (6 of 6 [100%]), followed by CELOX-A (5 of 6 [80%]), while no manual pressure was required in the case of PB (0 of 6 [0%]). Application time for PB (19.0 ± 4.6 seconds) was significantly less than CELOX-A (169.0 ± 73.5 seconds) and standard gauze (187.8 ± 1.7 seconds). CONCLUSION: We prepared a type of superabsorbent PAAs and made an original hemostatic dressing, PB. It can rapidly achieve durable hemostasis in the groin-penetrating trauma hemorrhage swine model without any external compression. The packet form makes PB easy to deploy and remove from wounds. Therefore, PB could be a promising hemostatic candidate for controlling penetrating hemorrhage.

Emergency approach to the femoral artery.

PURPOSE: The purpose of this study was to evaluate the applicability and potentially associated harms of emergency access to the femoral artery and vein in a sample of physicians working together in the emergency department of a level I trauma center. In addition, to investigate whether there are differences between participants in terms of different levels of training. METHODS: A sample of 36 orthopedic trauma and anesthesiology assistant doctors, specialists, and senior physician was recruited from the emergency room management at a level I trauma center in Graz, Austria. Emergency approach to the femoral vessels was performed on 33 fresh cadavers. Attention was paid to time, successful clamping of the vessels, self-assessment and learning curve. RESULTS: The approach was performed correctly in 97.2% (35/36) of all cases. 97.2% of all participants (35/36) were confident to perform the emergency access. They were proven right, since especially the resident and senior subgroups achieved satisfactory results concerning the correct performance of the approach to the femoral vessels as well as correct identification of the femoral artery and vein. CONCLUSION: In conclusion, we evaluated the emergency access to the femoral artery (FA) and femoral vein (FV) as an easily teachable procedure including high success rates (correct performance in 97.2%).

A patient with femoral artery pseudoaneurysm treated with ultrasound-guided injection of an exogenous lyophilized human fibrin sealant.

A femoral artery pseudoaneurysm (FAP) is a serious complication of arterial injury. It can cause compression of the surrounding nerves and tissues, rupture and bleeding of the aneurysm, and formation and dislodgement of thrombi, and can lead to distal limb embolism, tissue necrosis, and infection. Computed tomography angiography and ultrasonography are the preferred techniques for diagnosis of FAP. This report describes the successful treatment of an FAP using an ultrasound-guided percutaneous intracavitary injection of a lyophilized human fibrin sealant. This treatment was safe, associated with minimal pain and complications, and clinically effective.