Timing of trauma deaths due to uncontrolled bleeding have not changed in three decades: A multicenter study of patients in hemorrhagic shock.

Background: Effective hemorrhage control is essential in managing trauma and surgical patients, with uncontrolled bleeding being a leading cause of mortality. Ankaferd Blood Stopper (ABS), a hemostatic agent historically used in Anatolia, has gained recognition for its ability to modulate red blood cell-fibrinogen interactions to form a stable protein network for rapid bleeding cessation. Objective: This review explores the multifaceted applications of ABS, evaluating its efficacy, safety, and potential therapeutic roles across various medical fields, including hemostasis, wound healing, antimicrobial activity, and antineoplastic effects. Methods: A comprehensive synthesis of clinical trials, case reports, and experimental studies was conducted to assess the performance and implications of ABS. This narrative review highlights its application in trauma, surgery, dental procedures, and other clinical contexts, and compares its efficacy with that of established hemostatic agents. Results: ABS demonstrates significant efficacy in achieving hemostasis in diverse clinical settings, particularly in patients with coagulopathies. Its wound healing and antimicrobial properties enhance its therapeutic versatility. Neurotoxic effects of ABS are also reported, with recent studies providing mixed evidence on nerve safety in animal models. Emerging evidence suggests potential antineoplastic effects, with studies reporting apoptosis induction in cancer cells and protective effects in experimental models. Conclusion: ABS is a promising hemostatic agent with applications in bleeding control, wound healing, and infection management. While it has shown efficacy in various clinical settings, its safety profile remains a subject of debate, with some studies confirming its biocompatibility and others reporting potential neurotoxic effects. Further large-scale human studies are needed to clarify its long-term safety and establish standardized clinical guidelines for its use.

Rationale:Acute aortic syndromes, including dissection and aneurysm, are life-threatening vascular emergencies that often present with vague, nonspecific pain. Such pain may mimic common musculoskeletal or visceral disorders such as vertebrogenic, renal, or gastrointestinal pain, leading to diagnostic delays and adverse outcomes. This case series underscores how atypical vertebrogenic-like pain can conceal underlying aortic pathology and highlights the importance of early imaging in suspicious cases.Patient concerns:A 56-year-old man with descending thoracoabdominal aortic aneurysm, and 35-year-old man with Stanford Type A ascending aortic dissection.Diagnoses:CT angiography of the aorta due to persistent vertebrogenic back pain despite treatment of lumbar spine pathology revealing a large descending thoracoabdominal aortic aneurysm. In second case a CT scan of the cervical and thoracic spine performed after persistent pain despite cervical vertebrogenic syndrome analgesics treatment led to aortic dissection confirmation.Interventions:Elective surgical repair of aneurysm via thoraco-phreno-laparotomy. The aneurysm was resected and replaced with a 22-mm aorto-aortic Dacron graft. In second case, an emergency surgery with veno-arterial extracorporeal membrane oxygenation support with an open chest due to ongoing uncontrollable hemorrhage was provided.Outcomes:Patient was discharged on postoperative day 7 in stable condition. A second patient passed away of early complications as systemic inflammatory response syndrome, acute renal failure, and circulatory shock.Lessons:These cases emphasize the diagnostic challenges of aortic pathologies in the context of misleading clinical features. Physicians must maintain a high index of suspicion for acute aortic syndromes, particularly when encountering atypical or refractory pain in patients with cardiovascular risk factors. Early diagnosis and adherence to guideline-based management are critical to improving survival in these high-risk emergencies.

Abdominal trauma remains a major cause of preventable death, primarily due to uncontrolled hemorrhage and infection. Conventional hemostatic agents often prove inadequate for noncompressible wounds and can cause secondary damage. To address this, we developed a bioinspired multifunctional hydrogel by engineering quaternized carboxymethyl chitosan (QCMCS) and oxidized hyaluronic acid (OHA). QCMCS enhanced cationic hemostasis, significantly reducing blood loss and accelerating clotting versus a commercial sponge. Dopamine-grafted OHA (OHA-Dop) provided strong wet tissue adhesion. The hydrogel demonstrated rapid hemorrhage control in rat liver models and potent antibacterial activity (>99% reduction against E. coli and S. aureus). It also promoted tissue healing by fostering a regenerative microenvironment and activating relevant signaling pathways. This design effectively bridges emergency hemostasis with infection prevention, offering a promising strategy for managing complex abdominal trauma.

Uncontrolled bleeding after severe trauma poses a major challenge to existing tissue adhesives primarily due to their inadequate wet adhesion, sluggish bonding kinetics, insufficient mechanical strength, and potential cytotoxicity. Here, we report the development of an injectable and biocompatible hydrogel adhesive based on a unique catalyst-free cross-linked network of poly(disulfide)s. The incorporation of melanin nanoparticles (CINP) within the hydrogel matrix enhances its cross-linking density, thereby strengthening its tissue binding capabilities and imparting exceptional mechanical properties alongside robust wet adhesion. In vitro evaluations demonstrate the superior tissue adhesion, biocompatibility, and photoresponsive antibacterial properties of the CINP@PolyLA-Ch hydrogel. Furthermore, we showcase its hemostatic efficacy and intraorgan tissue adhesion performance in rat liver defect, rabbit liver and spleen injury, and rabbit cardiac puncture model. These findings underscore the potential of this hydrogel adhesive as an effective hemostatic agent for the emergency management of massive hemorrhage.

Bleeding disorders of unknown cause: A conglomeration of disorders with heterogeneous etiology.

Most potentially survivable combat deaths occur from hemorrhage. With the future potential for large scale combat operations, surgical treatment of wounded combatants will be delayed, necessitating prolonged prehospital care. We tested whether 6 hemostatic dressings could control junctional hemorrhage for up to 24 hours. Female Yorkshire swine were randomized into 9 groups: no intervention, non-hemostatic control gauze, Combat Gauze, Celox Gauze, ChitoGauze, Celox Rapid, Veriset, and CounterFlow Gauze.Following anesthesia, the femoral artery received arteriotomy, and a 45 second uncontrolled hemorrhage before treatment was applied. Animals were monitored for up to 24 hour or until euthanasia criteria were met. If the first 3 animals receiving each treatment did not survive 2 hour, the baseline survival threshold was not met and additional animals were not performed. Primary outcomes were survival time and 24 hour survival rate. All animals without intervention died (<30 minutes). Only Combat Gauze, Celox Gauze, Celox Rapid, and Veriset groups met the survival threshold and included 5 animals. Ranking by survival time was Veriset (19.4 ± 10.3 hour), Combat Gauze (16.7 ± 10.5 hour), Celox Gauze (15.1 ± 12.2 hour), and Celox Rapid (14.9 ± 12.4 hour). Veriset achieved 80% survival rate although each of the other 3 groups were 60%. Post-treatment estimated blood loss was least in Veriset (1.0% of body weight) and greatest in Celox Gauze (2.0%) groups. In this pilot study, Combat Gauze, Celox Gauze, Veriset, and Celox Rapid achieved survival beyond 2 hour in a fatal junctional wound. These should be considered for use in casualties with junctional hemorrhage especially under conditions requiring prolonged prehospital care.

Orthopedic surgery faces dual challenges of uncontrolled bleeding and poor bone regeneration at defect sites. While traditional beeswax-based hemostats remain clinically prevalent, their non-resorbability impedes healing and triggers chronic inflammation. This study introduces a "hemostasis-resorption-osteogenesis" synergistic design paradigm, developing a novel bioresorbable bone wax based on a polymer dispersion matrix that integrates a quaternized cationic starch (QS) and β-tricalcium phosphate (β-TCP) dual-phase promoting matrix (PST). PST bone wax's physicochemical properties, characterized via finger pressing models and in vitro sealing assays, demonstrate excellent plasticity and adhesiveness, enabling rapid sealing and prolonged hemostasis under physiological blood pressure. It gradually resorbs, releasing Ca2⁺/PO4 3 - ions that induce osteogenic differentiation in bone mesenchymal stem cells (BMSCs) and mineralization into hydroxyapatite (HA) crystals mimicking natural bone matrix. Hemocompatibility tests reveals its ability to adsorb erythrocytes and aggregate/activate platelets, effectively facilitating coagulation. In vivo experiments in rabbit and beagle models validate efficient hemostatic and osteogenic capabilities. Ultimately, PST bone wax achieves immediate hemostasis and long-term osteoregeneration through QS and β-TCP synergy, exhibiting favorable biocompatibility and safety, providing an innovative clinical solution with broad prospects.

Abstract Background: Laparoscopic cholecystectomy is the standard procedure for symptomatic gallstones. Significant vascular injuries, particularly to the portal vein, are rare but often fatal. Objective: To evaluate outcomes and prognostic factors of polytetrafluoroethylene (PTFE) tube graft reconstruction for portal vein following severe portal triad injury during laparoscopic cholecystectomy. Methods: This prospective study analyzed seven patients who underwent portal vein reconstruction using PTFE tube grafts after severe portal triad injuries during laparoscopic cholecystectomy. Patients were referred from peripheral hospitals due to uncontrollable bleeding. Comprehensive statistical analyses were performed on survival outcomes, perioperative parameters, metabolic derangements, and postoperative complications. Results: Among the seven patients, five died within 72 h postoperatively (71.4% mortality), while two survived. Primary causes of death included hepatic failure, multiorgan dysfunction, and sepsis. Multivariate analysis identified three independent predictors of mortality: vascular clamp time &gt;50 min (odds ratio [OR]: 5.8, P = 0.003), acute physiology and chronic health evaluation II score &gt;25 (OR: 4.2, P = 0.007), and lactate &gt;5 mmol/L at 12 h postoperatively (OR: 7.1, P &lt; 0.001). Nonsurvivors demonstrated significantly elevated liver enzymes (aspartate transferase: 1842 ± 435 vs. 563 ± 172 IU/L, P &lt; 0.001) and profound metabolic acidosis. Long-term follow-up of survivors (18–24 months) demonstrated excellent graft patency with minimal complications. Conclusion: PTFE tube grafts can be viable for portal vein reconstruction following severe portal triad injury, with survivors showing excellent long-term outcomes. Critical determinants of survival include vascular clamp time, severity of concurrent injuries, and timing of intervention. A multidisciplinary approach with standardized protocols for early recognition and rapid intervention may improve outcomes.

Rapid and effective hemorrhage control is critical in trauma and surgical interventions, where uncontrolled bleeding remains a leading cause of preventable death. In response to this urgent clinical demand, the development of novel hemostatic materials is the focus of increasing research interest, in both academia and industry. Styptic dressings are gradually evolving to address this need. However, significant challenges, such as delayed activation, suboptimal performance in severe conditions, and biocompatibility issues, persist. Here current limitations in hemostatic dressing technologies are explored, and recent innovations including biomimetic approaches in this field are highlighted. Special emphasis is placed on microparticle-integrated and nanoengineered systems integrated with drug delivery technologies. By addressing these challenges, it is aimed to inspire new pathways for the development of next-generation multifunctional dressings with enhanced efficacy and accessibility.

Injectable hemostatic foam hydrogel for traumatic intra-abdominal hemorrhage

A multifunctional self-gelling hemostatic powder based on synergistic non-covalent interactions for rapid hemostasis and infected wound healing.

Pragmatic Early Predictors of Survival After Trauma.

Despite the known haemostatic action of emicizumab (Hemlibra) in haemophilia A patients, its role in the prevention and control of bleeding in high-demand haemostatic situations, such as major surgery, remains to be determined. Patients receiving regular emicizumab prophylaxis often require concomitant factor VIII (FVIII) therapy during major surgery to prevent uncontrolled bleeding and to promote postoperative healing. However, there are limited prospective surgical data relating to concomitant FVIII and emicizumab use. Simoctocog alfa (Nuwiq) is a B-domain deleted recombinant FVIII produced in a human cell line without chemical modification or protein fusion with proven efficacy as surgical prophylaxis in adult and paediatric patients. The Nuwiq for Perioperative management Of patients With haemophilia A on Emicizumab Regular prophylaxis (NuPOWER) study aims to examine perioperative efficacy and safety of simoctocog alfa in haemophilia A patients on emicizumab prophylaxis undergoing major surgery. NuPOWER is a prospective, open-label, single-arm, multicentre study that will be conducted at approximately 15 centres worldwide. Up to 28 male patients ≥12 years with severe haemophilia A and no FVIII inhibitors will be recruited. All patients must be receiving regular emicizumab prophylaxis and scheduled to undergo a major surgical procedure during which concomitant simoctocog alfa will be administered. The primary endpoint is the overall haemostatic efficacy of simoctocog alfa, adjudicated by an independent data monitoring committee using a pre-defined algorithm, and will consider intraoperative and postoperative efficacy assessments by the surgeon and investigator, respectively. Secondary endpoints include intraoperative haemostatic efficacy, postoperative haemostatic efficacy, number of allogeneic blood products transfused, perioperative FVIII plasma levels (as measured by FVIII activity) and thrombin generation, and safety parameters. In the era of non-factor therapy, NuPOWER will generate valuable prospective data on concomitant use of simoctocog alfa and emicizumab prophylaxis in patients with severe haemophilia A undergoing major surgery. Ethical approval has been received from institutional review boards/independent ethics committees, and the study will be conducted in compliance with the Declaration of Helsinki. This work will be disseminated by publication of peer-reviewed manuscripts and presentations at scientific meetings. CT EU 2022-502060-21-00; NCT05935358.

Rational design of freeze-crosslinked polysaccharide sponges for efficient non-compressible hemostasis and liver repair.

Objectives: The objective of this study was to assess the safety of early active mobilization (EAM) in critically ill adults receiving vasopressor or inotropic support. Material and Methods: We conducted a prospective cohort study in a 10-bed intensive care unit in Colombia between September 2023 and November 2024. Eligible patients were adults ≥18 years with vasopressor or inotropic support for ≥2 h, stable dosing for ≥30 min, and the ability to follow simple commands (Glasgow Coma Scale score ≥13 or Richmond Agitation-Sedation Scale −2 to +1). Exclusion criteria were inability to perform active or assisted movement, severe hypoperfusion (lactate &gt;6 mmol/L), prone positioning, multiple-organ failure, uncontrolled bleeding, post-cardiac arrest status, or recent cerebral/cardiac ischemic events. Interventions followed the frequency, intensity, time, and type of exercise principle and included EAM activities based on individual clinical assessment. We evaluated patients using standardized scales and monitored cardiorespiratory responses. The primary outcome was safety, defined as the absence of adverse events during or immediately after EAM. Results: We included 24 patients (mean age 66.5 ± 13.5 years, 62.5% male). Primary diagnoses were septic shock (29%) and cardiogenic shock (29%). Norepinephrine was required in 75% of patients (median dose 0.13 μg/kg/min). During EAM, 50% received supplemental oxygen and 25% required mechanical ventilation. Mobilization activities included sitting at the edge of the bed (46%), standing (29%), sitting in a chair (17%), and remaining semi-Fowler (8%). No adverse events occurred during any session. Only minimal, clinically non-significant increases in diastolic blood pressure (P &lt; 0.05) and mean arterial pressure (P &lt; 0.05) were observed. Conclusions: EAM in patients appears safe in critically ill adults receiving vasopressor or inotropic support when guided by structured assessment protocols. These findings challenge current restrictive mobility practices and suggest potential benefits for patient recovery. Larger studies are needed to confirm safety and establish evidence-based mobilization guidelines for hemodynamically supported patients.

ABSTRACTTherapeutic treatment of lung nodules by ablation is a new field. Even though not considered standard of care, lung nodule ablation can be appropriate for select cases. Even though ablation is a safe and well‐tolerated procedure, bleeding is a potential complication. We introduce our stepwise approach through two cases on how we AIM (Anticipate/Adjust, Image, Manage) to prevent uncontrolled bleeding during Robotically Assisted Bronchoscopic Ablation: 1. Anticipate structures with high risk for bleeding and adjust accordingly, accounting for the needle ablation field; 2. Image: utilise cone beam CT before the first and after each ablation session to screen for bleeding; 3. Manage bleeding by pre‐emptively utilising Fogarty balloon occlusion.

Direct assessment of organ perfusion during hemorrhage is essential for effective interventions. Initial blood loss triggers compensatory mechanisms to preserve vital organ perfusion, but failure leads to decreased perfusion and injury. Vital signs provide indirect measures of cerebral health, while diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS) enable continuous, noninvasive monitoring of cerebral microvascular blood flow (CBF), cerebral blood volume (CBV), and oxygenation, offering real-time insights for detection and intervention. Adult swine models of controlled (30% blood volume reduction via syringe) and uncontrolled (partial hepatectomy) hemorrhage were studied. Systemic measures, i.e., blood pressure (BP), end-tidal CO2 (EtCO2), and heart rate, were compared with cerebral measures (CBF, CBV, and oxygenation) assessed by DCS-NIRS. Monitoring spanned 3 hours post-intervention, with periodic laboratory tests for injury confirmation. Systemic and cerebral hemodynamics were assessed pre-intervention, post-intervention, and during follow-up, revealing significant differences across timepoints for BP and cerebral measures (P < .05). BP, CBF, and CBV decreased post-intervention in both cohorts, with recovery during follow-up only in the controlled cohort, where relative blood flow index (rBFI), total hemoglobin (HbT), and oxygenated hemoglobin (HbO) showed large reductions post-blood loss (large positive effects) and partial recovery during follow-up (large negative effects); however, rBFI and HbO remained below baseline, indicating incomplete recovery of cerebral perfusion and oxygenation. In the uncontrolled cohort, rBFI, HbT, and HbO decreased significantly post-injury, with reductions persisting below baseline during follow-up, reflecting impaired cerebral perfusion and oxygenation. EtCO2 remained stable in the controlled cohort (χ2(2) = 3.8, P = .15) but varied significantly in the uncontrolled cohort (χ2(2) = 9.25, P < .01). Lactic acid levels differed significantly in both cohorts, while pH changes were significant only in uncontrolled hemorrhage. DCS-NIRS-derived biomarkers for cerebral hemodynamics reflect changes observed in BP in controlled and uncontrolled hemorrhage, thus supporting our previous findings of DCS-NIRS's ability to detect hemorrhagic shock.

Precision surface-immobilized peptide on graphene/chitosan composite sponge for rapid hemostasis of uncontrolled bleeding.

Okara cellulose-based multifunctional sponge with wet elastic deformation recovery for antibacterial, hemostatic, and antioxidant properties.