Bleeding Rates Research Articles

The application of interventional methods in control of blood loss during giant upper extremity tumor resection

BackgroundThe purposes of this retrospective study were to determine the efficacy of interventional methods in control of intraoperative blood losses and investigate the perioperative complications.MethodsThe cases of 44 patients in whom a giant upper extremity tumor had been operated between 2008 and 2022 were analyzed retrospectively. Of these, 29 patients were treated with interventional methods (Group A) and 15 were treated without (Group B). Group A was further divided based on the intervention methodss: Group C (combination of balloon occlusion and transarterial embolization [TAE], n = 11) and Group D (single TAE, n = 18). Within Group D, patients were categorized based on the timing of TAE relative to surgery into Group E (TAE on the same day as surgery) and Group F (TAE performed days before surgery). We compared demographic features, blood loss, ICU admission rates, and use of vasopressors during surgery.ResultsWe collected clinical records from 44 patients diagnosed with a giant upper extremity tumor who underwent surgery. Group sizes were as follows: A (29), B (15), C (11), D (18), E (7), and F (11). Tumor volumes in the interventional and non-interventional groups were similar (704.19 ± 812.77 cm³ vs. 1224.53 ± 1414.01 cm³, P = 0.127). Blood plasma transfusion was significantly higher in Group B compared to Group A (425.33 ± 476.20 ml vs. 155.90 ± 269.67 ml, P = 0.021). Although overall blood loss did not significantly differ between Group A and Group B (467.93 ± 302.08 ml vs. 1150 ± 1424.15 ml, P = 0.087), the rate of massive bleeding (defined as blood loss over 1000 ml) was lower in Group A (6.9% vs. 46.47%, P = 0.004). The proportion of minors (patients aged less than 18) in Group C was significantly higher than in Group D (27.7% vs. 0.00%, P = 0.045). The amount of RBC transfusion was also significantly higher in Group C compared to Group D (458.18 ± 292.22 ml vs. 164.44 ± 224.03 ml, P = 0.021). No significant perioperative complications were observed.ConclusionsInterventional techniques have been shown to reduce both blood loss and the necessity for blood transfusions in patients with large upper extremity tumors. Furthermore, no significant perioperative complications have been observed.

Intercambio guiado por farmacocinética de factores VIII de vida media estándar a factores VIII de vida media extendida pegilados en la terapia de la hemofilia A en práctica clínica

ObjectiveTo analyze the differences in pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life factor VIII (FVIII) to extended half-life pegylated FVIII in patients with severe/moderate hemophilia A on prophylaxis, one year before and after the switch in real-life. MethodThis is a single-center, comparative, observational, sequential, retrospective, and multidisciplinary study. Population pharmacokinetic models from the WAPPS-Hemo® application were used to calculate pharmacokinetic parameters and individualize prophylaxis. The annual rate of total and joint bleeds, joint health (Hemophilia Joint Health Score), plasma half-life and area under the curve ratios, FVIII consumption, administration frequency, and cost were analyzed. ResultsThirty-eight adult patients with hemophilia A who switched from standard half-life FVIII to extended half-life pegylated FVIII were analyzed. Significant improvements (p < 0.05) were observed in all pharmacokinetic parameters, with plasma half-life and area under the curve improvement ratios of 1.5 and 1.9, respectively, as well as reductions in annual total and joint bleeding rates were registered. A higher number of patients with zero total (16.0 vs. 29.0) and joint bleeds (23.0 vs. 33.0) was also observed. The median reductions in administration frequency and dose/kg/week were 30.0% and 19.7%, respectively, avoiding 44.3 infusions/patient/year, resulting in savings of 20,843 €/patient/year. Furthermore, joint health improved (23.0 vs. 21.0; p = 0.017), and target joints resolved after the switch. ConclusionsThe pharmacokinetically guided switch from standard half-life FVIII to pegylated FVIII demonstrated significant clinical benefits with reduced bleeding rates and improvements in joint health. Additionally, improvements in pharmacokinetic parameters were observed, allowing for reduced treatment burden by decreasing administration frequency, as well as lower consumption and costs.

The ETNA-AF Europe registry: 4-year data of edoxaban use in atrial fibrillation in the Italian real world compared to the European cohort

The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years. Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population. In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding. These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

Anticoagulation management in gynecologic brachytherapy patients with perioperative or chronic thromboembolic disease: A retrospective analysis

Women on chronic anticoagulation (AC) who require operative brachytherapy for gynecologic malignancies represent a clinical challenge, but no guidelines exist regarding patient selection for brachytherapy or their perioperative management. We aimed to understand the incidence of hemorrhagic and embolic events in our patients on chronic AC and suggest management strategies for this patient population. A retrospective, single institutional study of patients treated with operative, gynecologic brachytherapy from 2013 to 2023 was performed to identify patients on chronic AC. We determined indications for AC use, oncologic therapy characteristics, duration of AC interruption, and therapy outcomes. The primary aim was to determine perioperative embolic or hemorrhagic complications as measured by the Common Terminology Criteria for Adverse Events. Of 304 patients treated with operative implants, 32 (10%) were on chronic AC for venous thromboembolism (n = 25), or atrial fibrillation/flutter (n = 13). The most common malignancies were cervical (n = 15) and inoperable uterine (n = 11). Implants were intracavitary (n = 14), interstitial (n = 6), or hybrid (n = 12) with a median (range) of 2 (1-3) implants, 4 (2-5) fractions, and 2 (1-3) days of bedrest per implant. 63% (n = 20) had an epidural for analgesia. AC was held for a median 3 days in 94% (n = 30) prior to the operative implant, and pharmacologic DVT prophylaxis was used in 78% (n = 25). There were two grade ≥ 2 hemorrhagic events and no new embolic events. The rate of bleeding and embolic events was acceptable, and women on chronic AC should not be excluded from potentially lifesaving operative brachytherapy, including complex cases that require spinal analgesia and interstitial applicators.

Ultrasound-guided popliteal sciatic nerve block for surgical anesthesia in wound care patients with ongoing anticoagulant/antiaggregant therapy: A single-center, prospective study.

Ultrasound-guided peripheral nerve blocks may be a good alternative in patients under antithrombotic drugs. We evaluated the efficacy of ultrasound-guided popliteal sciatic nerve block in patients undergoing lower extremity wound debridement of whom antithrombotic drugs could not be stopped. We focused on hemorrhagic complications related to sciatic nerve block. Wound care patients followed by Cardiovascular Surgery Department scheduled for lower extremity wound surgery were included in this prospective observational study. Data was collected between March 2021 and September 2022. All patient were under antithrombotic therapy and discontinuation of anticoagulant drugs were not possible. Single-insertion and multiple-injection sciatic nerve block at popliteal region was applied to all patients under ultrasound guidance. Primary outcome was the rate of hemorrhage. Secondary outcomes were block onset times, block success and postoperative analgesia times. Data of 105 patients was evaluated, 87 were male and 18 were female. Mean patient age was 61.92 ± 10.06, mean patient body mass index was 25.68 ± 6.33. All patients were under 1 or more antithrombotic drugs. Only one minor hematoma was detected by postoperative ultrasonography control in 1 patient. Hemorrhage complication rate was 1 of 105 (% 0.95, 95% CI, 0.00024-0.051). Overall block success rate was 99.05%. Mean block onset time was 16.27 ± 5.69 minutes. Mean postoperative analgesia time was 19.5 ± 11.22 hours. Sciatic nerve block under ultrasound guidance using in-plane technique was safe and provided sufficient surgical anesthesia and postoperative analgesia for lower extremity wound debridement surgery in patients on antithrombotic drugs.

Indication-based analysis of laser interstitial thermal therapy: a propensity score-matched comparison of outcomes for brain tumor versus epilepsy indications.

Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to ablate abnormal tissue in a targeted fashion. It is most commonly used to treat epileptic foci, brain tumors, and radiation necrosis. This study aimed to compare immediate postoperative outcomes between these indications. This study analyzed clinical data from the Nationwide Readmissions Database (NRD) from 2016 to 2019 and identified 2234 patients who underwent LITT procedures using ICD-10 codes. The authors analyzed patient demographics, complications, discharge disposition, readmission rates, and mortality. Following propensity score matching, 317 patients treated for epilepsy and 323 patients treated for brain tumors were compared. The mean ages were similar (epilepsy: 45.7 vs tumor: 49.0 years, p = 0.55), as were the proportions of female patients (epilepsy: 45.4% vs tumor: 52.9%, p = 0.83), all-payer costs (p = 0.81), income quartiles (p = 0.58), insurance types (p = 0.70), frailty rates (p = 0.85), and comorbid disease burdens as assessed by ECI score (p = 0.73). No significant differences were observed in rates of hemorrhage (p = 0.1), pulmonary embolism (p = 0.32), or infection (p = 0.16). However, the tumor cohort had higher rates of deep vein thrombosis (3.4% vs < 3.15%, p = 0.045), nonroutine discharge (26.6% vs 16.4%, p = 0.04), and 1-year hospital readmission (32.5% vs 18.6%, p = 0.006). One-year mortality rates were similar (tumor: 3.4% vs epilepsy: < 3.15%, p = 0.08). While postoperative complications and 1-year mortality rates were similar among patients undergoing LITT for epilepsy and brain tumors, the tumor cohort experienced higher rates of deep vein thrombosis, nonroutine discharge, and 1-year hospital readmission.

Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial

Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff. This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing. Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff. Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors. Novo Nordisk.

Anticoagulation Use and Endovascular Thrombectomy in Patients with Large Core Stroke: A Secondary Analysis of the SELECT2 Trial.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887-894.

Comparison of Direct Oral Anticoagulants and Vitamin K Antagonists for Left Ventricular Thrombus: A Global Retrospective Study

IntroductionGuidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOAC) versus vitamin K antagonist (VKA) in managing left ventricular thrombus among patients with and without recent myocardial infarction. MethodsThis retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013, to December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days since the indexed event. ResultsA total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs. 13.7%, RR=0.859, 95% CI 0.816-0.905, p<0.001), major bleeding (4.8% vs. 5.3%, RR=0.902, 95% CI 0.829-0.982, p=0.018), and systemic embolism (3.5% vs. 4.2%, RR=0.841, 95% CI 0.762-0.928, p=0.001) compared to VKAs in overall cohort. Within acute coronary syndrome group (N=14,302), DOACs had lower stroke (12.3% vs. 14.4%, RR=0.860, 95% CI 0.791-0.935, p<0.0001) and systemic embolism (3.1% vs. 4%, RR=0.774, 95% CI 0.651-0.919, p=0.003) risks. For non-acute coronary syndrome group (N=24,162), DOACs had lower stroke (11.4% vs. 13.1%, RR=0.868, 95% CI 0.811-0.929, p<0.001) and major bleeding (4.8% vs. 5.5%, RR=0.877, 95% CI 0.787-0.977, p=0.017) risks. No significant differences in all-cause mortality were observed across groups. ConclusionDOACs demonstrated better safety and efficacy outcomes when compared to VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome.

Nondiabetic Fetal Macrosomia: Causes, Outcomes, and Clinical Management.

Fetal macrosomia (FM) is common in clinical practice and carries increased risk of adverse maternal and neonatal health outcomes. Maternal diabetes mellitus (DM) is a well-known cause of macrosomia with significant research and guidelines focusing on macrosomia in this population. Less is known about causes, prevention, and clinical management for suspected FM in individuals without diabetes. The objective of this review is to describe the risk factors associated with nondiabetic FM, review risks associated with macrosomia in pregnancy, and potential treatment considerations for this condition. Original research articles, review articles, and guidelines on macrosomia were reviewed. Risk factors for macrosomia in patients without DM include previous delivery of an infant with macrosomia, excessive pregnancy weight gain, and obesity. Maternal complications of FM include higher rates of cesarean delivery, postpartum hemorrhage, and vaginal laceration. Fetal complications include shoulder dystocia, decreased Apgar scores, and increased risk of childhood obesity. Exercise during pregnancy has been shown to reduce the risk of FM. Induction of labor prior to 39 weeks is not recommended in the setting of suspected macrosomia as there is a lack of adequate evidence to support that this decreases adverse neonatal or maternal outcomes. In addition, elective cesarean delivery for suspected macrosomia is not recommended to be considered unless estimated fetal weight is greater than 5000 g in the absence of DM. Delivery of an infant with macrosomia in patients without DM has increased maternal and fetal risks. Predicting infants who will meet criteria for macrosomia is challenging. More research is needed to identify ways to accurately estimate fetal weight, interventions to prevent macrosomia, and additional ways to mitigate risk in patients without DM who have suspected FM.

To bridge or not to bridge: the role of intravenous thrombolysis in mechanical thrombectomy for large cerebral infarctions through a two-center cohort study and meta-analysis

BackgroundThe effectiveness and safety of intravenous thrombolysis before mechanical thrombectomy (MT) in large cerebral infarctions remains uncertain. This study compares bridging MT, which includes intravenous thrombolysis, to direct MT without it. MethodsData from 298 patients with anterior circulation large cerebral infarctions, assessed via non-enhanced CT (ASPECTS 0-5), who underwent MT in two-center cohort studies, were analyzed. Primary outcomes focused on independent ambulation (modified Rankin Scale scores 0-3) at 90 days post-stroke. Safety outcomes included parenchymal hemorrhage (PH) rates and mortality. We conducted a sensitivity analysis considering the timing from symptom onset to imaging within 4.5 hours. Additionally, a meta-analysis of 17 studies involving 3527 patients assessed the interventions' effectiveness and safety, with further scrutiny of high-quality studies (Newcastle-Ottawa Scale ratings 7-9) to increase robustness of results. ResultsNo significant differences were found in 90-day independent ambulation between the bridging MT and the direct MT group (adjusted odds ratio [aOR] 1.15, 95% CI 0.68-1.94). Rates of PH and mortality were also similar across groups. These outcomes were consistent in the subgroup imaged within 4.5 hours of symptom onset. The meta-analysis supported these outcomes, showing no improvement in ambulation (aOR 1.16, 95% CI 0.82-1.64) or reduction in PH with bridging MT. Further analysis of high-quality studies supported these results. ConclusionsThe cohort study and meta-analysis provide Class II evidence indicating no significant differences in functional outcomes or hemorrhagic risks between bridging and direct MT for large cerebral infarctions. This suggests that direct MT might be a viable alternative to bridging MT.

Acquired Hemophilia A: A Narrative Review and Management Approach in the Emicizumab Era

Acquired Hemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies to factor VIII (FVIII). The goals of treatment are two-fold, namely immunosuppressive therapy (IST) to eradicate the inhibitor and hemostatic management to control bleeding. Emicizumab, a bispecific antibody that acts as a factor VIIIa (FVIIIa) mimetic, has seen growing use in AHA following its approval for congenital hemophilia A (cHA). This review provides an overview of the epidemiology, pathophysiology, diagnosis, and treatment of AHA. Registry, trial, and case series data are assimilated and summarized with an emphasis on a standardized approach that integrates the use of emicizumab. With recent registry data suggesting the need to focus on immunosuppression-related mortality in AHA, we provide treatment recommendations in an algorithmic format that have become the standard of care at our institution. These recommendations are intended to minimize hemostatic product usage and potential toxicity related to IST, while reducing morbidity and re-hospitalization rates for bleeding. The proposed treatment algorithm, which includes key interventions by phase of therapy, can be readily implemented at centers that have rapid access to plasma FVIII activity using a one-stage assay. A case is presented to illustrate the proposed diagnostic and management considerations.

The impact of OCEANIC-AF and the future of factor XIa inhibitors

The OCEANIC-AF trial was terminated early due to inferiority of asundexian compared with apixaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation.1 However, the promisingly low bleeding rates support continued exploration of factor XIa inhibitors. Future efforts should focus on achieving greater factor XIa inhibition and identifying patient populations that may benefit most from these therapies.

Breaking boundaries: exploring recent advances in anticoagulation and thrombosis management: a comprehensive review.

Thromboembolic disorders globally contribute to morbidity and mortality, emphasizing adequate anticoagulation and thrombosis management. Therapeutic advances are essential in preventing complications like pulmonary embolism, stroke, and myocardial infarction. This review summarizes recent anticoagulation advances, current challenges, future directions, and novel anticoagulants and drug delivery systems on clinical outcomes. This paper assesses the effectiveness and safety of new anticoagulants through a systematic review of recent clinical trials, meta-analyses, and guideline publications. Key studies, including PACIFIC-AF, RIVER, ENAVLE, ENVISAGE-TAVI AF, and ARCADIA, were analyzed to provide a perspective on therapeutic advancements. The review highlights key findings from vital clinical trials. Asundexian, in the PACIFIC-AF trial, demonstrated a 34% reduction in bleeding events compared to Apixaban. In the RIVER trial, Rivaroxaban reduced significant bleeding events by 20% compared to warfarin in patients with bioprosthetic mitral valves. In the ENAVLE trial, Edoxaban achieved a 3.7% decrease in thromboembolic events compared to warfarin without increasing significant bleeding rates. In the ENVISAGE-TAVI AF trial, edoxaban was noninferior to VKAs in preventing thromboembolic events but showed a slight increase in major bleeding events by 1.5%. Lastly, the ARCADIA trial highlighted that apixaban did not significantly reduce recurrent stroke risk compared to aspirin, with both treatments having an annualized stroke rate of 4.4%. Advances in anticoagulant therapies and drug delivery systems aim to enhance patients' clinical outcomes for thromboembolic disorders. While recent trials show promising data, ongoing patient-specific responses and monitoring challenges require further research. Continuous innovation and investigation are essential to refine anticoagulation practices and tailor treatments.

Closure of gastric mucosal defects using the reopenable-clip over the line method to decrease the risk of bleeding after endoscopic submucosal dissection: a multicenter propensity score-matched case-control study (with video)

Background and AimsEndoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric cancer. However, post-ESD bleeding presents significant risks. Closing mucosal defects following ESD may reduce the incidence of post-ESD bleeding. Currently, no optimal closure method exists. Therefore, we invented clip-line closure using the reopenable-clip over the line method (ROLM) and evaluated its efficacy in preventing post-ESD bleeding. MethodsWe retrospectively reviewed data from patients who underwent gastric ESD between January 2012–March 2024. Patients were categorized into two groups: the non-closure group (mucosal defect remained unclosed) and the ROLM group (defect was closed using ROLM). Baseline characteristics of patients, distribution of bleeding risk factors, and incidence and timing of post-ESD bleeding were compared between the groups. Propensity score matching was employed to minimize potential bias. ResultsFollowing propensity score-matching, 162 ESDs were performed for 168 lesions in the non-closure group, whereas 160 ESDs were performed for 168 lesions in the ROLM group. The mean long diameter of the mucosal defects, procedure time for ROLM, and number of clips required for ROLM were 45.9 mm, 35.6 min, and 33.2, respectively. All mucosal defects resulting from the ESD were fully closed using ROLM. The post-ESD bleeding rate in the ROLM group was significantly lower (1.8%, 3/168 lesions) than in the non-closure group (7.7%, 13/168 lesions, p = 0.02). ConclusionsROLM is feasible for mucosal defect closure following gastric ESD and effectively prevents post-ESD bleeding in high-risk patients, addressing a significant gap in existing methods.

From the INVICTUS Trial to Current Considerations: It’s Not Time to Retire Vitamin K Inhibitors Yet!

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

035. Short-Term Outcomes for Catheter-Directed Thrombolysis for Non-Threatening Acute Limb Ischaemia: A Systematic Review and Meta-Analysis

Background: Acute limb ischemia (ALI) is a rapid reduction in arterial blood flow to a limb, which may jeopardize its viability, particularly in sensory loss or motor impairment. Catheter-directed thrombolysis (CDT) is the preferred treatment in numerous centers for patients with marginally threatening acute limb ischemia (ALI). This meta-analysis examined the short-term effects of catheter-directed thrombolysis (CDT) for patients with non-imminent limb ischemia. Methods: We searched PubMed, ScienceDirect, and the Cochrane Library to locate observational papers and trials published from 2014 up to early 2024 that report on the outcomes of CDT in patients with ALI. The outcome of this study was mortality rate, amputation rate, and major bleeding. We utilized R Studio to perform the meta-analysis. Results: Nine trials were included, involving 1,067 patients receiving CDT for non-imminent acute limb ischemia. Our results indicate that the pooled mean short-term amputation rate was 10% (95% CI [0.06; 0.15], p &lt; 0.01), the major bleeding rate was 5% (95% CI [0.00; 0.09], p = 0.03), and the short-term death rate was 4% (95% CI [0.03; 0.06], p = 0.08). Our findings indicate a low incidence of short-term death, amputation, and major bleeding in patients undergoing CDT. Conclusion: This meta-analysis reveals a low incidence of short-term mortality, amputation, and major bleeding in patients undergoing Catheter-directed thrombolysis. Further investigations are necessary to determine if CDT should be utilized for the revascularization of limbs with non-urgent ischemia.

Use of Direct Anticoagulants in Kidney Transplant Recipients: Review of the Current Evidence and Emerging Perspectives.

Thromboembolic events and atrial fibrillation are common among kidney transplant recipients (KTRs), and these conditions typically require anticoagulation. Traditionally, vitamin K antagonists were used for management, but the use of direct oral anticoagulants (DOACs) has increased in KTRs. In the general population, DOACs are recommended over warfarin, but the applicability of these recommendations to KTRs is unclear because of risk-benefit concerns. There is some hesitancy to use DOACs in KTRs because of their dependence on renal clearance for elimination, potential drug-drug interactions, and limited data. To date, studies of DOACs in KTRs have demonstrated that they are efficient in thromboembolic events, major bleeding is rare, and drug-drug interactions appear rare. However, no guidance yet exists about the use of DOACs, reversal of DOAC action, and the pre- and post-kidney transplant management of DOACs in KTRs, and the evidence base is scarce. Thus, decisions on DOAC use in KTRs are based on expert opinion and the resources and experiences of individual transplant centers. This review summarizes 10 published studies on the use of DOACs in 741 KTRs, evaluating the side effects, efficacy, drug-drug interactions, and perioperative management compared with those of 1320 KTRs using vitamin K antagonists. Although current data are limited, DOACs appear to be relatively safe and effective in KTRs, with some studies suggesting lower bleeding rates and better kidney function than with vitamin K antagonists. However, more research with larger patient groups is needed to draw definitive conclusions.

A Moving Target: Studying the Effect of Continuous Transcutaneous CO2 Monitoring in ELBW Infants During an Equipoise Shift.

Objectives: To assess whether continuous non-invasive pCO2 monitoring by transcutaneous pCO2 monitor (TCpCO2) among extremely low birth weight (ELBW) premature infants, during the first week of life, will decrease the rate of high-grade intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) or the combined outcome of IVH/PVL and death. Methods: This was a prospective, observational, multicenter study. Due to ethical constraints, allocation was based on TCpCO2 monitor availability. ELBW infants were either monitored by TCpCO2 monitor (Sentec, Therwil, Switzerland) (study group), or recruited to the control group if a TCpCO2 monitor was not available. Results: A total of 132 ELBW infants participated in the study. The size of the study group (106 infants) and the control group (26 infants) differed because monitor availability increased during the study period reflecting change in standard of care. The groups had comparable gestational age and baseline characteristics. No difference was found in the rate of IVH/PVL in the study vs. control groups (10% vs. 4%; p = 0.7, respectively), or in the combined outcome of PVL/IVH and death (16% vs. 15%; p = 1.0, respectively). Conclusions: This study demonstrates the challenges in conducting a prospective controlled trial in a rapidly evolving medical field. While the study began with a clear equipoise, this balance shifted as the care team gained more experience with TCpCO2 monitoring among the study population, despite the absence of new clinical evidence to justify such a shift. Consequently, the small control group limited our ability to draw definitive conclusions regarding the study's objective. However, our findings may increase awareness of continuous non-invasive pCO2 monitoring in extremely premature infants.

Endovascular therapy in patients with acute intracranial non-terminal internal carotid artery occlusion (ICA-I).

Acute intracranial occlusion of the internal carotid artery (ICA) can be distinguished into (a) occlusion of the terminal ICA, involving the proximal segments of the middle or anterior cerebral artery (ICA-L/-T) and (b) non-terminal intracranial occlusions of the ICA with patent circle of Willis (ICA-I). While patients with ICA-L/-T occlusion were included in all randomized controlled trials on endovascular therapy (EVT) in anterior large vessel occlusion, data on EVT in ICA-I occlusion is scarce. We thus aimed to evaluate effectiveness and safety of EVT in ICA-I occlusions in comparison to ICA-L/-T occlusions. A large international multicentre cohort was searched for patients with intracranial ICA occlusion treated with EVT between 2014 and 2023. Patients were stratified by ICA occlusion pattern, differentiating ICA-I and ICA-L/-T occlusions. Baseline factors, technical (modified thrombolysis in cerebral infarction (mTICI) scale) and functional outcomes (modified Rankin scale [mRS] at 3 months) as well as rates of (symptomatic) intracranial hemorrhage ([s]ICH) were analyzed. Of 13,453 patients, 1825 (13.6%) had isolated ICA occlusion. ICA-occlusion pattern was ICA-I in 559 (4.2%) and ICA-L/-T in 1266 (9.4%) patients. Age (years: 74 vs 73), sex (female: 45.8% vs 49.0%) and pre-stroke functional independency (pre-mRS ⩽ 2: 89.9% vs 92.2%) did not differ between the groups. Stroke severity was lower in ICA-I patients (NIHSS at admission: 14 [7-19] vs 17 [13-21] points). EVT was similarly successful with respect to technical (mTICI2b/3: 76.1% (ICA-I) vs 76.6% (ICA-L/-T); aOR 1.01 [0.76-1.35]) and functional outcome (mRS ordinal shift cOR 1.01 [0.83-1.23] in adjusted analyses. Rates of ICH (18.9% vs 34.5%; aOR 0.47 [0.36-0.62] and sICH (4.7% vs 7.3%; aOR 0.58 [0.35-0.97] were lower in ICA-I patients. EVT might be performed safely and similarly successful in patients with ICA-I occlusions as in patients with ICA-L/-T occlusions.