Fatal Hemorrhage Research Articles

Development of self-gelling powder combining chitosan/ bentonite nanoclay/ sodium polyacrylate for rapid hemostasis: In vitro and in vivo study.

Although hemostatic powders are commonly used in clinical and emergency settings, they frequently show poor absorption, raise cytotoxicity issues, and are not effective for fatal non-compressible bleeding. The purpose of this research is to create a self-gelling hemostatic powder based on chitosan, bentonite, and sodium polyacrylate (CBS) to improve the hemostatic effect. When liquid comes into contact with CBS powders, they can fuse and form a stable hydrogel in less than 30s. Here, the concentration of the superabsorbent polymer is the primary determinant of the self-gel's creation. CBS groups exhibited excellent in vitro biocompatibility and hemocompatibility. In terms of bleeding and hemostatic time, the in vivo hemostatic results demonstrate the superiority of CBS-3 powder (∼57s in rat liver avulsion model) and (∼64s in rat tail amputation model) over a commercial product group called ARISTA. Additionally, the fabricated CBS powders can quickly absorb large amounts of blood, which can also aggregate platelets and blood cells. After four weeks of rat liver implantation, CBS-3 significantly accelerated the angiogenesis and wound healing processes. Thus, the hemostatic CBS self-gelling powder could be an effective solution for treating blood loss and liver wounds.

Fatal intracranial hemorrhage in acid sphingomyelinase deficiency: A case report highlighting the role of managing comorbidities

Fatal intracranial hemorrhage in acid sphingomyelinase deficiency: A case report highlighting the role of managing comorbidities

Vitamin K at Birth: A Must to Prevent Fatal Bleeding in Infants, but Do We Know the Right Dose?

Vitamin K at Birth: A Must to Prevent Fatal Bleeding in Infants, but Do We Know the Right Dose?

Delayed Aneurysm Rupture Following Endovascular Treatment with Contour Device: A Case Report.

Delayed rupture of intracranial aneurysms after endovascular treatment is a rare but serious complication. We report the first documented case of late aneurysmal rupture following treatment with a Contour intrasaccular device. A patient in their 60s with a basilar tip aneurysm underwent endovascular treatment using a 14-mm Contour device. Fifteen months later, the patient presented with a fatal intraventricular hemorrhage, and imaging revealed device displacement and aneurysm growth. This case underscores the importance of meticulous device sizing and follow-up, especially for large aneurysms.

P0764 Are anticoagulants safe in patients with Inflammatory Bowel Disease?

Abstract Background Inflammatory bowel disease (IBD) patients may have a higher risk of gastrointestinal bleeding during anticoagulant treatment due to mucosal erosions. Millions of patients worldwide receive classic oral anticoagulants or direct-acting anticoagulants (DOACs).The main indication is stroke prophylaxis in atrial fibrillation (AF), with an increasing prevalence in older age groups (8.5% of the Spanish population over 60 years old).Anticoagulants (especially DOACs) safety data are limited in IBD. Our objective was to evaluate the bleeding risk in IBD concerning these treatments. Methods A single-center retrospective study was conducted, collecting clinical characteristics, laboratory parameters and bleeding events. Bleeding risk was compared in two cohorts of IBD patients over 60 years old, treated with anticoagulants or not matched by age, sex, and type of IBD at a ratio of 2 controls for each anticoagulated case. We classified the severity of bleeding events as major or not according to the International Society on Thrombosis and Haemostasis criteria. Major bleeding is defined as fatal or symptomatic bleeding in a critical organ, with a decrease of 2 g/dL in hemoglobin or transfusion of 2 or more units. Chi-square test and Student's t-test were used to compare qualitative or quantitative variables respectively Results 186 subjects were analyzed (62 anticoagulated, 124 were not): 110 had ulcerative colitis (UC) and 76 Crohn's disease (CD). Baseline characteristics are described in Table 1. Of the 62 anticoagulated patients, 69% were on DOACs (26 apixaban,7 edoxaban,6 rivaroxaban,4 dabigatran)26% on classic oral anticoagulants and 5% on low molecular weight heparin. The main indication was AF (66%), followed by thrombosis (26%) and stroke (8%). No statistically significant differences were found in sex, age, location, behavior (CD), or extent of the disease, which was expected since controls were matched for these factors. There were 17 hemorrhagic events (9.1%) and 58,8% were major. The main bleeding cause was gastrointestinal (64.7%) followed by urinary (23.5%). Bleeding was significantly higher with anticoagulation (17.7 vs 4.8%, p=0.004) and specifically with NOACs (20.9 vs 4.8%; p=0.001). Analyzing only the bleeding cases, no statistically significant differences were found in the incidence of major bleeding, need for admission, iron therapy or transfusion with classic anticoagulants or NOACs, nor in hemoglobin or inflammatory parameters (Table 2). All cause mortality was higher in anticoagulated patients (19.4 vs 6.5%; p= 0.007); one case was 2º to digestive bleeding Conclusion IBD patients may have a higher risk of gastrointestinal bleeding during anticoagulant treatment (specifically DOACs), so they may require closer monitoring References -S. Schulman, C. Kearon. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost., 3 (2005), pp. 692-694 http://dx.doi.org/10.1111/j.1538-7836.2005.01204.x | Medline -Cea-Calvo L, Redón J, Lozano JV, et al. Prevalencia de fibrilación auricular en la población española de 60 o más años de edad. Estudio PREV-ICTUS. Rev Esp Cardiol. 2007; 60: 616-24 -Gu ZC, Wei AH, Zhang C, Wang XH, Zhang L, Shen L, Li Z, Pan MM, Liu XY, Pu J, Lin HW. Risk of Major Gastrointestinal Bleeding With New vs Conventional Oral Anticoagulants: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2020 Apr;18(4):792-799.e61. doi: 10.1016/j.cgh.2019.05.056. Epub 2019 Jun 11. PMID: 31195162. -Viola A, Chiappetta MF, Scolaro M, Bignoli F, Versace A, Fries W. Direct oral anticoagulants increase the risk of anaemia and hospitalization in IBD patients with active intestinal disease. Dig Liver Dis. 2020 Dec;52(12):1525-1526. doi: 10.1016/j.dld.2020.08.033. Epub 2020 Sep 6. PMID: 32900651.

Combination Antithrombotic Therapy for Reduction of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease.

Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy. This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged ≥40 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study. A total of 101 participants were randomized. Average enrollment was 10 participants/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (±10.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32-1.93]; P=0.59) favoring the intervention. A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04142125.

A Real-World, Prospective, Observational Study of Rivaroxaban on Prevention of Stroke and Non-Central Nervous Systemic Embolism in Renally Impaired Korean Patients With Non-Valvular Atrial Fibrillation: XARENAL.

Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15-49 mL/min). XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30-49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15-29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m². The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA₂DS₂-VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m² per year. XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice. ClinicalTrials.gov Identifier: NCT03746301.

Compound heterozygous mutations (p.L68R∗37 and p.T241N) lead to abnormal protein levels and structures in hereditary FVII deficiency.

Congenital factor VII (FVII) deficiency is a genetic disorder characterized by decreased FVII activity, which sometimes leads to fatal bleeding. Numerous variants have been found in FVII deficiency, but mutations vary among patients. Each mutation deserves further exploration for each patient at risk of bleeding. We previously reported a Chinese patient with p.L68R∗37 and p.T241N compound heterozygous mutations. In this study, we further investigated the impact of these two mutations on the FVII expression through in vitro expression experiments. Mutations were introduced into the FVII coding region using site-directed mutagenesis, and recombinant FVII was combined with two different plasmids, and then quantitative PCR and western blot analyses were performed subsequently. The p.L68R∗37 mutation had no effect on mRNA levels but caused a significant decrease in protein levels. In the p.T241N mutant vector, mRNA levels did not show a noticeable decrease, but protein levels exhibited a slight decrease. Structural analysis revealed that the p.T241N mutation resulted in an altered secondary structure and protein instability, indicating impaired functional properties. Our study demonstrated that the p.L68R∗37 and p.T241N mutations impacted the protein levels and function of FVII, ultimately leading to a severe reduction in FVII activity. This study may contribute to further understanding of the molecular pathogenesis of FVII deficiency and offer insights for genetic counseling.

Use of ISTH bleeding assessment scale to evaluate therapy-associated bleeding risk in patients undergoing coronary revascularization

Background — Currently, there is a challenge in the dynamic prognostic assessment of haemorrhagic risks, particularly in recognising the development of bleeding in patients who have undergone cardiac surgery (CS). Bleeding frequently occurs in post-CS patients as they are receiving antithrombotic therapy (ATT), prescribed for continuous a period of 3, 6, or 12 months after surgery. This not only worsens prognosis and quality of life but also, if therapy is discontinued, increases the risk of thrombotic events. Objective — To investigate the diagnostic value of scales for assessing bleeding and predicting bleeding outcomes in individuals who have undergone myocardial revascularisation, and to assess the applicability of the ISTH scale for evaluating bleeding in this patient group. Methods — A total of 98 patients undergone myocardial revascularisation participated in the prospective study. An assessment of hemorrhagic risks according to the PRECISE-DAPT scale and hemorrhagic manifestations according to the ISTH scale was performed at visit 1 and 2 (0-1 month after revascularization). Results — It was found that the assessment of bleeding risk during antithrombotic therapy (ATT) in the first month after myocardial revascularisation, when performed using the PRECISE-DAPT scale, is not comparable to the assessment using the ISTH scale. However, the ISTH scale proved to be a useful tool for evaluating haemorrhagic complications of ATT in patients following cardiac surgery (CS). Conclusion — The use of the ISTH scale allows the assessment of early signs of bleeding during dual antiplatelet therapy (DAPT) following revascularisation, helping to foster a proactive attitude in patients towards monitoring complications of antithrombotic therapy. This approach can reduce risks of fatal haemorrhages and the development and progression of anaemia. However, the ISTH scale is not comparable to the PRECISE-DAPT scale for assessing hemorrhagic risks and cannot be recommended for dynamic prediction of hemorrhagic risks in post-CS patients.

Emergency pancreaticoduodenectomy with portal vein reconstruction using polytetrafluoroethylene graft for fatal duodenal malignant ulcer bleeding due to pancreatic cancer: an aggressive, but precise surgical approach.

Emergency pancreaticoduodenectomy with portal vein reconstruction using polytetrafluoroethylene graft for fatal duodenal malignant ulcer bleeding due to pancreatic cancer: an aggressive, but precise surgical approach.

Retrospective study of partial lateral corpectomy to treat thoracic and lumbar intervertebral disc herniation in 12 cats

Objectives The aim of this study was to describe the safety and effectiveness of thoracic or lumbar partial lateral corpectomy (PLC) in cats with spinal cord compression due to intervertebral disc herniation (IVH). Methods A retrospective study was conducted of 12 client-owned cats from two academic and one private referral veterinary centres. Cross-sectional imaging was available in 12 cats for evaluation of disc herniation. Nine cats had postoperative imaging for evaluation of slot creation and decompression. Neurological examination was performed for assessment of pre- and postoperative status. Complications were evaluated. Results Seven cats had severe (>50%), four moderate (>20 to <50%) and one mild (<20%) spinal cord compression on cross-sectional imaging. IVH occurred at Th12–13 in five cases, at L1–2 in two cases and at Th3–4, Th13–L1, L4–5 and L5–6 in one case each. After PLC, two cats had insufficient decompression (>20% remaining spinal cord compression), five had good decompression (<20% remaining spinal cord compression) and complete decompression (normal shape of the spinal cord) was achieved in two cats. Outcomes included five cats with an excellent result, three with significant improvement, one with mild improvement and three cats that died intra- or postoperatively due to extensive intraoperative bleeding. One cat was euthanased as a result of neurological deterioration 5 months postoperatively. The median follow-up period was 13.2 months (range 0 days to 84 months). Conclusions and relevance PLC in cats offers a potential treatment option for IVH to decompress the spinal cord. Fatal haemorrhage associated with this surgery is a significant risk, as occurred in 25% of the cats in this study. Surgeons should especially be aware of the potential for intraoperative haemorrhage and the need for sufficient slot creation to achieve sufficient spinal cord decompression and avoid complications.

Veno-arterial extracorporeal membrane oxygenation under dual antiplatelet therapy, immediately after craniotomy

Introduction: Extracorporeal membrane oxygenation (ECMO) is often considered a relative contraindication for traumatic brain injury and cerebral hemorrhage because fatal intracranial hemorrhage can occur. Moreover, dual antiplatelet therapy (DAPT)-related cerebral hemorrhage is associated with a high mortality rate. Herein, we report a case in which the patient was placed on ECMO under DAPT and managed without anticoagulation immediately after craniotomy. Case Report: A 51-year-old man was hospitalized for surgery for Moyamoya disease. The surgery was performed as scheduled; however, the patient experienced cardiac arrest while awakening from anesthesia. After return of spontaneous circulation, during the emergency percutaneous coronary intervention (PCI), he was placed on ECMO for cardiac arrest which caused an electrical storm. Because computed tomography (CT) after PCI revealed a new cerebral hemorrhage, ECMO was managed with DAPT without anticoagulation. Subsequently, the CT showed no increase in hematoma; however, a thrombus was observed in the membrane of the ECMO, and ECMO was withdrawn on the 4th intensive care unit day. Conclusion: Anticoagulation therapy with or without DAPT should not be used because of the risk of bleeding associated with veno-arterial ECMO immediately after craniotomy. Additionally, the risk of thrombosis may be high; therefore, additional care must be taken, and it is necessary to manage the ECMO circuit to consider the possibility of early replacement it too.

Programmed cell death-related ABI1 is a critical mediator of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by localized dilation of the abdominal aorta, posing a significant risk of rupture and fatal hemorrhage. While surgical and endovascular repair techniques have advanced, the underlying mechanisms driving AAA development remain unclear, hindering the development of effective preventive and therapeutic strategies. Using bioinformatics analysis of publicly available data sets, the study identified a strong correlation between cell death (CD) score and different types of programmed cell death scores in AAA samples. WGCNA analysis revealed a module enriched in genes related to proteasome-mediated protein degradation, nuclear envelope, and endocytosis, significantly correlated with CD score. Further analysis identified ABI1 as a dominant feature gene, highlighting its potential role in AAA pathogenesis. In vitro validation using an Angiotensin II-induced AAA model in human aortic smooth muscle cells demonstrated that siRNA-mediated knockdown of ABI1 significantly reduced cell apoptosis, migration, and the expression of pro-apoptotic proteins, confirming ABI1's crucial role in promoting CD and AAA progression. The findings suggest that ABI1 may represent a promising therapeutic target for the prevention and treatment of AAA. Further research is warranted to fully understand the role of ABI1 in AAA and to develop targeted therapies based on this promising target.

Abstract 4144581: Diltiazem, Direct Oral Anticoagulants and Risk of Major Bleeding in Patients with Atrial Fibrillation

Background: Existing research suggests a potential increase in bleeding risk associated with the combined use of calcium channel blockers (CCBs) and direct oral anticoagulants (DOACs). However, the evidence remains inconclusive and conflicting. To clarify this relationship, we conducted a meta-analysis to investigate the risk of major bleeding in patients with atrial fibrillation (AF) using diltiazem. Methods: We conducted a comprehensive search of major electronic databases, including PubMed, Embase, and the Cochrane Library, from their inception through April 20, 2024 for relevant studies. The primary endpoint was major bleeding, defined as a composite of bleeding-related hospitalization, requiring blood transfusion, or fatal bleeding. We conducted a conventional meta-analysis using the Hartung-Knapp-Sidik-Jonkman random-effects model. Endpoints are expressed as hazard ratio (HR) and their corresponding confidence intervals (CI). Results: A total of 5 studies with 488,884 patients with AF were included in our study, of which 23.4% of patients were on diltiazem. All patients were also on DOACs. Results of the meta-analysis showed that there was no statistically significant difference between use of diltiazem and the risk of major bleeding (HR 1.16 ; 95% CI 0.94-1.42). Sensitivity analysis showed that this result remained unaltered in terms of magnitude and direction after excluding one study at a time. When stratified by type of control group, both active comparator (HR 1.09 ; 95% CI 0.92-1.30) and non-use subgroups (HR 1.24 ; 95% CI 0.87-1.77) showed that there was no significant difference in the risk of major bleeding with diltiazem use respectively. Conclusion: We observed that there was no significant difference in the risk of major bleeding in diltiazem use compared to controls in AF patients on DOACs. Further large-scale, longitudinal, and prospective studies are essential to validate these findings.

Abstract 4135791: Bleeding risk with non-vitamin K antagonist oral anticoagulants versus single antiplatelet therapy: A systematic review and meta-analysis of randomized controlled trials

Background: While non-vitamin K antagonist oral anticoagulants (NOACs) are more effective than single antiplatelets (mostly low-dose aspirin) at reducing stroke risk in patients with atrial fibrillation (AF), differences in bleeding risk between NOACs and single-dose antiplatelets across various populations remain unclear. Aim: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing bleeding outcomes of NOACs versus single antiplatelet therapy. Methods: We searched MEDLINE, EMBASE, and CENTRAL to June 2024 for RCTs that compared NOAC (therapeutic doses used for stroke prevention in AF patients) versus single antiplatelet therapy for a treatment duration of ≥3 months. For the meta-analyses, we used fixed-effects models and reported results as summary risk ratios (RRs). We used Risk of Bias 2 and GRADE to assess the quality and certainty of the evidence. Results: Eight RCTs with 26,194 participants were included. Mean follow-up time was 18 (±13) months. NOACs included in the studies were apixaban (4 studies), rivaroxaban (2 studies), and dabigatran (2 studies). All studies used low-dose aspirin as the comparator. When compared to aspirin, NOACs had a higher risk of major bleeding (326/13107 [2.5%] vs. 239/13087 [1.8%] events; RR 1.36 95% CI 1.15-1.60, I 2 =52%, 8 trials; high certainty) (Figure A), gastrointestinal bleeding (104/8803 [1.2%] vs. 74/8788 [0.8%] events; RR 1.39; 95%CI, 1.04-1.87; I 2 =0%; 5 trials; high certainty), and clinically relevant non-major bleeding (318/10397 [3.1%] vs. 230/10395 [2.2%] events; RR 1.38; 95%CI, 1.17-1.63; I 2 =16%; 5 trials; high certainty). There was no difference in the risk of intracranial hemorrhage (88/13107 [0.7%] vs. 84/13087 [0.6%] events; RR 1.04, 95%CI 0.78-1.41; I 2 =48%; 9 trials; high certainty) (Figure B) nor fatal bleeding (22/12412 [0.2%] vs. 28/12392 [0.2%] events; RR 0.78; 95%CI, 0.45-1.36; I 2 =8%; 6 trials; high certainty). Conclusion: When compared to aspirin, NOACs are associated with an increased risk of major bleeding and clinically relevant non-major bleeding, but not intracranial hemorrhage. These data are important to inform patients about the risks of antithrombotic treatment.

RADT-30. MANAGEMENT OF PRESUMED PSEUDOPROGRESSION WITH EARLY BEVACIZUMAB IN THE THREE MONTHS AFTER HIGH DOSE RADIATION THERAPY FOR GLIOBLASTOMA

Abstract BACKGROUND Optimal management for symptomatic steroid-refractory pseudoprogression (rPsP) following IMRT for Glioblastoma remains poorly defined. This study examined radiological volumetric response and clinical outcomes following use of early Bevacizumab (earlyBEV), defined as commencing during or within 3 months of IMRT. METHODS Consecutive patients managed with Stupp60Gy IMRT between 2016-2023 for Glioblastoma were analysed for those patients receiving earlyBEV for rPsP. Volumetric analysis was performed with sequential MRI T1gd/T2 sequences using preBEV and postBEV scans. Primary endpoint was volumetric reduction of T1gd/T2 volumes at month+2/3 postBEV. Clinical response, overall survival and pattern of relapse, specifically distant failure was assessed. RESULTS Forty-one (14%) of 289 patients received earlyBEV for rPsP, with median follow-up of 9.9months (q1-3:8-25) for survivors. Compared to remaining 248 patient cohort, earlyBEV had worse initial ECOG0,1 (50%vs76%); less near-total resection (5%vs42%); and less MGMT methylation (35%vs46%). Additionally at diagnosis the initial tumours had larger T1gd and T2 volumes. Median time to commencement of earlyBEV was 1.4months postIMRT; including seven patients during IMRT. All patients responded to BEV, with reduction in symptoms, steroid use and radiological volume, though one died pre-assessment. Median T1gd and T2 volumes before earlyBEV were 37cm3 (q1-3:23-63cm3) and 116cm3 (q1-3:90-148cm3) respectively, which were 95% and 78% larger than at diagnosis. Median survival postBEV was 8.1months (95%CI:7.5-8.6). Median volumes postBEV reduced to 16cm3 (q1-3:8-23cm3) and 41cm3 (29-55cm3); which was a percentage reduction for T1gd and T2 of 57% and 65%. Midline shift reduced from 5mm(q1-3:3-8mm) to zero in two-thirds of patients. Patients requiring earlyBEV had worse survival compared to remaining cohort (p<0.001); with median OS 11.9months (95%CI:10.4-13.5) vs 19.9months (95%CI:18.4-21.5). A component of distant relapse was evident in 48% of earlyBEV vs 34% in remaining cohort. One serious adverse event occurred with fatal intracranial haemorrhage day10 after initial BEV dose. CONCLUSION This study data confirms efficacy of earlyBEV for managing steroid-refractory pseudoprogression, but also the worse prognosis of this high-risk cohort.

A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Military medicine of modern hybrid wars

During the hybrid armed conflict in which Russia became involved — the Special Military Operation — the medical service of the Armed Forces faced a number of challenges. This review analyzes foreign publications indexed in PubMed® concerning the conditions and factors affecting the activities of the medical services of armed forces, primarily those of NATO countries. It was revealed that a limiting factor for operational effectiveness is the staffing levels and qualitative composition of medical personnel, their preparedness to provide care for the specific pathologies of wartime, and maintaining these competencies in an up-to-date state. Important conditions for successful provision of medical care are preserving the integrity of medical facilities during targeted attacks on them, and the ability to use infrastructure in hostile or newly occupied territories. Prehospital care serves as a limiting factor in reducing lethality, with the main causes being fatal hemorrhages and head injuries from mine-blast trauma. Proper tourniquet application, rapid evacuation, and blood transfusions make the greatest contribution to reducing prehospital mortality. Among casualties, those with limb wounds are most significant, as they subsequently create the greatest social burden on the state, exceeding the “years lived with disability” parameter for all other disease classes, including oncological and cardiovascular diseases. In modern conflicts, the most dangerous in terms of lethality are mine-blast injuries (61.4–83.5%) and head injuries (20.9–59.0%), and in terms of subsequent disease burden, limb injuries (45.7%) constitute an absolute majority and are the point of focus for the main efforts of the medical services of the warring states’ armed forces. At the same time, there are no unified approaches regarding the place of application of qualified and specialized care among countries.

A novel dynamic risk score to predict Clinically Significant Bleeding (CSB) after 3 months of anticoagulation in patients with incident Venous ThromboEmbolism (VTE) and without active cancer

Abstract Background Predicting the risk of clinically significant bleeding (CSB), bleeding requiring hospitalisation or fatal bleeding, during and following anticoagulation is complex. Current models lack the ability to adapt to changing patient conditions over time and fail to account for the direct impact of anticoagulation in real-world clinical settings. Purpose To develop a dynamic risk prediction model for CSB to help clinicians decide on the duration of anticoagulant therapy in conjunction with a model for recurrences of VTE (also submitted to the conference). Methods UK Clinical Practice Research Datalink data (2001-2020) was used to generate a retrospective cohort with first VTE who had received 3 months of anticoagulation. Patient episodes of CSB and recurrent VTE were evaluated. Covariates were collected at baseline and subsequently as time-varying data to capture changes post-VTE. Hazards with 95% confidence intervals (CI) were estimated and covariates included in a Fine & Gray model used as predictors of CSB. An additive (logarithmic) scoring scheme was developed from subdistribution hazard ratios, discrimination (expressed by the C-statistic) estimated from 10-fold cross-validation. Results 51,621 patients with a first VTE were included; 3307 CSB were identified in 206,292 person-years of observation. Incidence rates for CSB were 1.60 per 100 person-years. 18 independent predictors of CSB (recorded before or after the VTE diagnosis) were included in the model, Table 1. Patients recognised as lower-risk, medium and higher-risk (67.5 %, 15.9 % and 16.7 % of the population, respectively, at 90 days after first VTE, assuming no anticoagulation treatment) had an annualised incidence rate of 0.84, 2.94, and 9.45 per 100 person-years. The C-statistic for CSB was 0.78 (95%CI, 0.77-0.79). The points scored can be added to predict risk (Table 2). Conclusions Our dynamic score effectively identifies patients at risk of CSB three months post their initial VTE diagnosis. It allows for continuous monitoring of risk, and modelling of treatment impact, providing clinicians with a pragmatic tool to help determine treatment duration, and adapt their strategies in response to evolving patient conditions.Table 1:Predictors for CSBTable 2:CSB risk score

Efficacy and safety of the ultraslow low-dose thrombolytic regimen for mechanical prosthetic valve thrombosis: a prospective cohort study

Abstract Background Mechanical prosthetic valve thrombosis (MPVT) remains a significant and life-threatening complication. While surgery is here considered the gold standard therapy, it has a high perioperative risk in the acute setting. Preliminary evidence suggests that an ultraslow low-dose thrombolytic regimen may offer a safer and equally effective alternative compared to both conventional fast-infusion thrombolytic approaches or surgical options. Purpose We aimed at evaluating efficacy and safety of a previously described ultraslow low-dose thrombolytic regimen for treating acute MPVT in hospitalized adult patients. Methods This prospective single-center cohort study included all consecutive adult patients with acute MPVT treated with our ultraslow low-dose thrombolytic regimen. Patients with contraindication to thrombolytic therapy or left-sided MPVT with a minimum thrombus size of 0.8 cm2 or severe dyspnea with NYHA FC IV were excluded, and considered candidate to surgery. The regimen here used consisted of 25 mg rtPA infused over 25 hours. If initially failed, a repeat 6-hour infusion of 25 mg rtPA was administered up to a maximum total cumulative dose of 150 mg or until an adverse event occurred. The primary objective was the rate of complete MPVT resolution, defined as >75% reduction in the obstructive gradient by transthoracic echocardiography, less than 10 degrees residual constraint in opening and closing valve motion angles as quantified by fluoroscopy, and alleviation of patients’ thrombosis-associated symptoms or signs. Results From April 2018 to November 2023, 135 infusions of thrombolytic therapy were administered in 118 patients (median age: 35 years (IQR, 25-49); 59 [50%] women) (Table 1). 12 patients had more than one episode of MPVT during the study period. Obstructive prosthetic valve thrombosis occurred in 89.6% (121/135) of cases. Pulmonary valves were most frequently affected (n = 84, 62.2%), followed by tricuspid (n = 34, 25.2%), mitral (n = 10, 7.4%), and aortic (n = 7, 5.2%) valves. A complete thrombolysis success was achieved in 119/135 episodes of thrombolytic therapy (88.1%); of these, 47/119 patients (39.5%) responded after the first thrombolytic dose. The median total dose administered was 50 mg (IQR, 25-75) over a median infusion duration of 30 hours (IQR, 25-36). Four patients responded partially to the regimen, six patients were candidates for bailout surgery, and only one fatal intracranial bleeding occurred. No other thromboembolic or bleeding adverse events were observed. Conclusion This is the largest prospective evaluation on the safety and efficacy of the ultraslow low-dose thrombolytic regimen, which proved highly effective - in this prospective cohort - in achieving prosthetic valve thrombosis resolution with minimal complications. Further larger clinical trials are warranted.Table 1- baseline CharacteristicsStudy Outcomes