Search Results (41)

Traumatic injury remains a major cause of death worldwide, with bleeding being one of its most critical and life-threatening consequences. Whole-body computed tomography (WBCT) has become a standard diagnostic method in trauma settings; however, timely interpretation remains challenging for acute care physicians. In this study, we propose a new automated method for detecting traumatic bleeding in CT images using a three-dimensional object detection model enhanced with an atrous spatial pyramid pooling (ASPP) module. Furthermore, we incorporate a false positive (FP) reduction approach based on multi-organ segmentation, as developed in our previous study. The proposed method was evaluated on a multi-institutional dataset of delayed-phase contrast-enhanced CT images using a six-fold cross-validation approach. It achieved a maximum sensitivity of 90.0% with 587.3 FPs per case and a sensitivity of 70.0% with 46.9 FPs per case, outperforming previous segmentation-based methods. In addition, the average processing time was reduced to 4.2 ± 1.1 min. These results suggest that the proposed method enables rapid and accurate bleeding detection, demonstrating its potential for clinical application in emergency trauma care. Full article

Current αIIbβ3 antagonists are potent antithrombotic agents, their clinical use is limited by the risk of life-threatening bleeding. Emerging evidence has highlighted key mechanistic differences between thrombosis and hemostasis, opening avenues for safer antithrombotic strategies. Targeting integrin αIIbβ3 outside-in signaling has been proposed to mitigate bleeding risk; however, the short half-life of peptide-based therapeutics remains a major challenge. In this study, we developed an optimized αIIbβ3 antagonist, KGDRR—a recombinant mutant protein derived from snake venom disintegrin, incorporating an Arg55 residue within the KGD loop—through systematic structure–activity relationship (SAR) analysis. Molecular docking revealed a critical cation–π interaction between Arg55 of KGDRR and Tyr122 of the β3 subunit, stabilizing integrin αIIbβ3 in an unliganded-closed conformation. Functionally, KGDRR selectively inhibited thrombus propagation by blocking ligand binding and downstream Gα13-mediated outside-in signaling while preserving initial thrombus core formation, which is a limitation of current αIIbβ3 inhibitors. Unlike conventional antagonists, KGDRR maintained αIIbβ3 in an unliganded-closed conformation without inducing the integrin activation and conformational change that lead to immune-mediated platelet clearance and thrombocytopenia. In animal models, KGDRR effectively suppressed thrombus growth without causing thrombocytopenia or prolonging bleeding time. Furthermore, intramuscular administration of KGDRR achieved a functional half-life 3.5 times longer than that of the clinically used antithrombotic eptifibatide at equivalent antithrombotic efficacy. In conclusion, KGDRR exhibits potent antithrombotic activity with a favorable safety profile and enhanced pharmacokinetic stability. These findings position KGDRR as a promising next generation αIIbβ3 antagonist with the potential to improve clinical outcomes in antithrombotic therapy. Full article

Background/Objectives: Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries and imposes an increasing burden on aging populations. Although transcatheter aortic valve implantation (TAVI) has transformed the treatment of severe AS, current guidelines do not differentiate management based on gender. This study aimed to investigate gender-based differences in procedural complications and one-year clinical outcomes in patients treated with next-generation self-expandable TAVI devices. Methods: This retrospective, multicenter international registry included 3862 consecutive patients who received either the ACURATE neo or Evolut R/Pro valve. Patients were stratified by gender; propensity score matching (PSM) adjusted for baseline differences. The primary endpoint was a composite of all-cause mortality or stroke at one year. Secondary endpoints included major vascular complications, major or life-threatening bleeding and acute kidney injury (AKI). Results: Of 3353 patients included (64.5% female), women were older (82.3 ± 5.6 vs. 81.1 ± 6.2 years, p < 0.001) and had higher STS scores (5.2 ± 3.9 vs. 4.5 ± 3.4%, p < 0.001). In the unmatched population, major vascular complications occurred in 7.7% of females versus 4.1% of males (p < 0.001), life-threatening bleeding in 2.8% vs. 1.4% (p = 0.016) and AKI in 8.5% vs. 5.7% (p = 0.009). After PSM, the primary endpoint was more frequent in females (9.4% vs. 6.0%, p = 0.014), largely driven by stroke (2.8% vs. 1.2%, p = 0.024), while overall mortality was similar (11.3% vs. 9.5%, p = 0.264). Conclusions: Despite comparable long-term survival, female patients undergoing TAVI with self-expandable valves experience higher rates of procedural complications, notably stroke and major vascular events. These findings underscore the need for tailored procedural strategies to improve outcomes in female patients. Full article

Background: Trauma is a major global public health concern. Many countries are working to reduce preventable deaths; however, the mortality rate remains higher than their goal, indicating a need for continuous development in trauma care, including further improvements across the system. This article explores recent developments and updated guidelines for both prehospital emergency care and in-hospital trauma management, emphasizing evidence-based and patient-centered approaches. Current concepts: In the prehospital phase, the primary focus is on early and aggressive hemorrhage control using techniques such as tourniquet application, wound packing, and permissive hypotension as standard practices. Advancements in this field, including intraosseous vascular access and tranexamic acid administration, have improved patient outcomes. The emphasis on structured assessments, particularly “circulation, airway, breathing” (CAB) assessments, underscores the importance of managing life-threatening hemorrhages. During the in-hospital phase, the primary focus is on controlling bleeding. Protocols emphasize the judicious administration of fluids to prevent over-resuscitation and mitigate the risk of exacerbating coagulopathy. Efficient transfusion strategies are implemented to address hypovolemia, while ensuring balanced ratios of blood products. Furthermore, the implementation of advanced interfacility transfer systems and communication tools such as “Situation, Background, Assessment, Recommendation” (SBAR) plays a pivotal role in optimizing patient care and reducing delays in definitive treatment. Discussion and Conclusions: This review highlights the importance of implementing advanced strategies to align with international standards and further decrease the rate of preventable trauma-related deaths. Strengthening education and optimizing resource allocation for both prehospital and hospital-based trauma care are essential steps toward achieving these objectives. Full article

Background: Gastrointestinal bleeding (GIB) is a common complication of left ventricular assist device (LVAD) support. The UTAH bleeding risk score (UBRS) is the only dedicated GIB prediction model, but its efficacy has not been confirmed in an external validation cohort. Furthermore, the reliability of other bleeding risk scores, such as ARC-HBR and HASBLED, has never been tested in this specific population. This study aims to validate the UBRS and compare its accuracy with the ARC-HBR and HASBLED scores. Methods: Major adverse events (MAEs) and bleeding events of 75 consecutive patients who had undergone LVAD implantation between 2010 and 2021 at a referral hospital for a heart transplant were retrospectively analyzed. The accuracy of the UBRS, ARC-HBR and HASBLED scores was evaluated using a ROC curve model. Results: At a mean follow-up of 905.9 ± 724 days, 58 (77.3%) patients had an MAE and 28 (37.3%) had a major bleeding event. Out of the 39 major bleeding events, the majority were GI (43%) and intracranial bleeding (33.3%). Compared with patients without major bleeding, those who experienced major bleeding showed a lower survival probability, regardless of the nature of the bleeding (GIB vs. other bleeding events). The UBRS effectively stratified the bleeding risk with an AUC of 0.86. In contrast, the ARC-HBR and HASBLED scores demonstrated lower discriminatory power, with AUCs of 0.61 and 0.52, respectively. Conclusions: UBRS accuracy was confirmed in our study population. Gastrointestinal bleeding is a common life-threatening complication and one of the main causes of re-hospitalization during VAD support, leading to a lower patient survival probability. Full article

Background: Early safety outcomes following transcatheter aortic valve implantation (TAVI) for severe aortic stenosis are critical for patient prognosis. Accurate prediction of adverse events can enhance patient management and improve outcomes. Aim: This study aimed to develop a machine learning model to predict early safety outcomes in patients with severe aortic stenosis undergoing TAVI. Methods: We conducted a retrospective single-centre study involving 224 patients with severe aortic stenosis who underwent TAVI. Seventy-seven clinical and biochemical variables were collected for analysis. To handle unbalanced classification problems, an adaptive synthetic (ADASYN) sampling approach was used. A fined-tuned random forest (RF) machine learning model was developed to predict early safety outcomes, defined as all-cause mortality, stroke, life-threatening bleeding, acute kidney injury (stage 2 or 3), coronary artery obstruction requiring intervention, major vascular complications, and valve-related dysfunction requiring repeat procedures. Shapley Additive Explanations (SHAPs) were used to explain the output of the machine learning model by attributing each variable’s contribution to the final prediction of early safety outcomes. Results: The random forest model identified left femoral artery diameter and aortic valve calcification volume as the most influential predictors of early safety outcomes. SHAPs analysis demonstrated that smaller left femoral artery diameter and higher aortic valve calcification volume were associated with poorer early safety prognoses. Conclusions: The machine learning model highlights of early safety outcomes after TAVI. These findings suggest that incorporating these variables into pre-procedural assessments may improve risk stratification and inform clinical decision-making to enhance patient care. Full article

Major bleeding is a life-threatening condition with high morbidity and mortality. Trauma, gastrointestinal bleeding, haemoptysis, intracranial haemorrhage or other causes of bleeding represent major concerns in the Emergency Department (ED), especially when complicated by haemodynamic instability. Severity and source of bleeding, comorbidities, and prior use of anticoagulants are pivotal factors affecting both the clinical status and the patients’ differential response to haemorrhage. Thus, risk stratification is fundamental in the initial assessment of patients with bleeding. Aggressive resuscitation is the principal step for achieving haemodynamic stabilization of the patient, which will further allow appropriate interventions to be made for the definite control of bleeding. Overall management of major bleeding in the ED should follow a holistic individualized approach which includes haemodynamic stabilization, repletion of volume and blood loss, and reversal of coagulopathy and identification of the source of bleeding. The aim of the present practical guide is to provide an update on recent epidemiological data about the most common etiologies of bleeding and summarize the latest evidence regarding the bundles of care for the management of patients with major bleeding of traumatic or non-traumatic etiology in the ED. Full article

Background: Significant intraoperative and postoperative blood loss are rare but possibly life-threatening complications after lung resection surgery either during open or minimally invasive procedures. Microporous Polysaccharide Haemospheres (ARISTA™AH) have demonstrated time-efficient haemostasis, lower postoperative blood volumes and a lower blood transfusion requirement, without any identified adverse events across other specialities. The primary aim of our study was to evaluate the impact of ARISTA™AH on short-term postoperative outcomes in thoracic surgery. Our secondary aim was to compare ARISTA™AH with other commonly used haemostatic agents. Methods: We retrospectively reviewed a prospectively collected database of consecutive early-stage lung cancer patients surgically treated in two European centres (October 2020–December 2022). Exclusion criteria included open surgery, patients with coagulopathy/anticoagulant medication, major intraoperative bleeding, non-anatomical lung resection and age <18 years. The cohort was divided into five groups according to the haemostatic agent that was used. Propensity score matching was used to estimate the effect of ARISTA™AH on various intra- and postoperative parameters (continuous and binary outcome modelling). Results: A total of 482 patients (M/F:223/259; VATS 97/RATS 385) with a mean age of 68.9 (±10.6) years were analysed. In 253 cases, ARISTA™AH was intraoperatively used to control bleeding. This cohort of patients had a significant reduction in total drain volume by 135 mls (standard error 53.9; p = 0.012). The use of ARISTA™AH did reduce the average length of a hospital stay (−1.47 days) and the duration of chest drainage (−0.596 days), albeit not significantly. In the ARISTA™AH group, we observed no postoperative bleeding, no blood transfusion requirement, no 30-day mortality and no requirement for redo surgery. The use of ARISTA™AH significantly reduced the odds of postoperative complications, as well as the need for transfusion and redo surgery. Conclusions: Our data showed that Microporous Polysaccharide Haemospheres are a safe and effective haemostatic device. Their use has a positive effect on the short-term postoperative outcomes of patients surgically treated for early-stage lung cancer. Full article

In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients’ conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents. Full article

The coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most common symptoms of COVID-19 are respiratory symptoms, but some patients develop severe thrombotic complications. Studies have looked into the association between the disease severity in COVID-19 patients and polymorphisms in the genes encoding prothrombotic and cardiovascular risk factors. The presented rare case describes inflammatory and acute thrombotic complications with musculoskeletal involvement in a patient with combined coagulation genetic defects. A 37-year-old woman was hospitalized with a respiratory infection of coronavirus etiology complicated by pneumonia and pulmonary embolism and confirmed using computed tomography and elevated D-dimer. Sixteen days after discharge, she developed deep vein thrombosis after discontinuation of antiplatelet and anticoagulant therapy due to bleeding. Four months after infection, we found bilateral avascular necrosis of the femoral head. The patient had a miscarriage with considerable blood loss and was given genetic testing, which confirmed the presence of a combined defect with a risk of both thrombosis and bleeding—heterozygous for the Leiden G1691A mutation, homozygous for the 677C>T mutation (MTHFR), heterozygous for the Val34Leu (factor XIII) mutation, and 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor 1 (PAI-1) genes. The described rare clinical case poses a serious challenge regarding the anticoagulant and antiplatelet therapy, especially in the presence of thrombotic complications in COVID-19 and the underlying genetic defect associated with a risk of bleeding, including life-threatening intracranial bleeding. More research is needed to better understand the major medical concern about antithrombotic treatment in COVID-19 patients with bleeding risk in the context of genetic coagulation disorders. The case raises the vigilance of clinicians to search for a genetic predisposition to the development of severe thrombotic events in COVID-19 patients with no other known underlying diseases. Full article

Direct endoscopic necrosectomy (DEN) is a challenging procedure for the debridement of walled-off pancreatic necrosis (WOPN), which may be complicated by several adverse events, primarily bleeding which may require radiological embolization or even surgery. The lack of dedicated devices for this purpose largely affects the possibility of safely performing DEN which increases the risk of complications. We present the case of a 63 years-old man who underwent an endoscopic ultrasound (EUS)-guided drainage of a WOPN, and who was readmitted one month after stent removal with clinical, endoscopic, and radiological signs of infected necrosis involving the splenic artery. A second EUS-guided drainage was performed, with clear visualization of the arterial vessel in the midst of a large amount of solid necrosis. Due to the high risk of major bleeding during DEN, a hybrid procedure in the angiographic room was performed, in order to identify and avoid, under fluoroscopic control, the splenic artery during the entire procedure guide, which was successfully performed using the EndoRotor system. We hereby review the current literature regarding DEN using the EndoRotor system. The case reported, with a literature overview, may help the management of these patients affected by benign but life-threatening conditions which involve a multidisciplinary setting. Full article

Objectives: We aimed to evaluate the efficacy and safety of low-dose protamine in reducing access site-related complications during Transcatheter Aortic Valve Implantation (TAVI) as compared to full-dose protamine. Background: Access site-related complications represent an independent predictor of poor outcomes of TAVI. Data regarding heparin reversal with protamine and the dosage needed to prevent bleeding complications are scarce among patients undergoing TAVI. Methods: A total of 897 patients were retrospectively included in the study. Patients who underwent percutaneous coronary intervention within 4 weeks before or concomitantly with TAVI (n = 191) were given 0.5 mg protamine for each 100 units of unfractionated heparin. All other patients (n = 706) were considered as a control group and 1 mg protamine for each 100 units of heparin was administered. Results: The combined intra-hospital endpoint of death, life-threatening major bleeding, and major vascular complications were significantly more frequent in patients receiving low-dose protamine [29 (15.2%) vs. 50 (7.1%), p < 0.001]. After propensity matching (n = 130 for each group) for relevant clinical characteristics including anti-platelet therapy [19 (14.6%) vs. 6 (4.6%), p = 0.006], low-dose protamine predicted the combined endpoint (OR 3.54, 95%-CI 1.36–9.17, p = 0.009), and even in multivariable analysis, low-dose protamine continued to be a predictor of the combined endpoint in the matched model (OR 3.07, 95%-CI 1.17–8.08, p = 0.023) alongside baseline hemoglobin. Conclusions: In this propensity-matched retrospective analysis, a low-dose protamine regime is associated with a higher rate of major adverse events compared to a full-dose protamine regime following transfemoral TAVI. Full article

Background: While current clinically administered anticoagulant medications have demonstrated effectiveness, they have also precipitated significant risks: severe bleeding complications including, but not limited to, gastrointestinal hemorrhaging and intracranial and other life-threatening major bleedings. An ongoing effort is being made to identify the best targets for anticoagulant-targeted drugs. Coagulation factor XIa (FXIa) is emerging as an important target of current anticoagulant treatment. Objective: This review will summarize the development of anticoagulants and recent advances in clinical trials of experimental factor XI inhibitors from a clinical application perspective. Results: As of 1 January 2023, our search screening included 33 clinical trials. We summarized the research progress of FXIa inhibitors from seven clinical trials that evaluated their efficacy and safety. The results showed no statistically meaningful distinction in the primary efficacy between patients receiving FXIa inhibitors compared to controls (RR = 0.796; 95% CI: 0.606–1.046; I² = 68%). The outcomes did not indicate a statistical difference in the occurrence of any bleeding between patients receiving FXIa inhibitors compared to controls (RR = 0.717; 95% CI: 0.502–1.023; I² = 60%). A subgroup analysis found significant differences in severe bleeding and clinically relevant hemorrhaging in subjects receiving FXIa inhibitors compared to Enoxaparin (RR = 0.457; 95% CI: 0.256–0.816; I² = 0%). Conclusions: Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants. Full article

Background: The initiation of extracorporeal membrane oxygenation (ECMO) is associated with complex inflammatory and coagulatory processes, raising the need for systemic anticoagulation. The balance of anticoagulatory and procoagulant factors is essential, as therapeutic anticoagulation confers a further risk of potentially life-threatening bleeding. Therefore, our study aims to systematize and analyze the most recent evidence regarding anticoagulation monitoring and the thromboembolic events in patients receiving veno-arterial ECMO support. Methods: Using the PRISMA guidelines, we systematically searched the Scopus and PubMed databases up to October 2022. A weighted effects model was employed for the meta-analytic portion of the study. Results: Six studies comprising 1728 patients were included in the final analysis. Unfractionated heparin was used for anticoagulation, with an activated partial thromboplastin time (aPTT) monitoring goal set between 45 and 80 s. The majority of studies aimed to investigate the incidence of adverse events and potential risk factors for thromboembolic and bleeding events. None of the authors found any association of aPTT levels with the occurrence of thromboembolic events. Finally, the most frequent adverse events were hemorrhage (pooled 43%, 95% CI 28.4; 59.5) and any kind of thrombosis (pooled 36%, 95% CI 21.7; 53.7), and more than one-half of patients did not survive to discharge (pooled 54%). Conclusions: Despite the tremendous development of critical care, aPTT-guided systemic anticoagulation is still the standard monitoring tool. We did not find any association of aPTT levels with thrombosis. Further evidence and new trials should clarify the true incidence of thromboembolic events, along with the best anticoagulation and monitoring strategy in veno-arterial ECMO patients. Full article

People with hemophilia (PWH), especially severe hemophilia, often experience bleeding episodes, which occur mostly at major joints. Intramural hematoma of the gastrointestinal (GI) tract is a rare, potentially life-threatening clinical bleeding manifestation in PWH. Prompt identification and timely administration of clotting factor concentrates are of utmost importance for effective management and optimal patient outcomes. In this report, we present the case of a 48-year-old male with severe hemophilia A. The patient developed a spontaneous intramural hematoma of the jejunum, leading to signs of acute abdomen, bloody stool, and paralytic ileus. Conservative management with factor VIII (FVIII) infusion was successfully administered. However, within a span of three months, the patient suffered from a recurrent episode of intramural hematoma, which was again effectively treated with conservative therapy. Subsequently, prophylactic FVIII therapy was administered to the patient, resulting in the absence of recurrence for over three years. Inspired by this case, we conducted a comprehensive review of the relevant literature and gathered data from 79 reported cases of intramural hematoma that were documented between the years 1956 and 2022. We classified these cases based on the site affected within the gastrointestinal (GI) tract (spread across five different locations) and proceeded to conduct a simple pooling analysis on the data collected, which subsequently revealed that the overall mortality rate of intramural hematoma in people with hemophilia (PWH) was found to be 12.2%, while children have a higher mortality rate (23.3%) than adults (4.9%). We hope this case report and literature review increase awareness of this rare bleeding manifestation in PWH, the effectiveness of conservative treatment, and the possibility of prophylaxis against recurrence. Full article