Lower Bleeding Research Articles

Non-variceal Upper Gastrointestinal Bleeding and Its Endoscopic Management.

Upper gastrointestinal bleeding (UGIB) is a major cause of morbidity and mortality. Clinical symptoms that patients may present with include: hematemesis, coffee-ground emesis, melena, and hematochezia. Clinical signs can range from tachycardia to shock. The anatomical landmark that differentiates upper gastrointestinal (GI) bleeds from lower bleeds is the ligament of Treitz. The first steps of treating a patient who presents with signs of UGIB are resuscitation with appropriate fluids and blood products as necessary. The consideration of endoscopy and the urgency at which it should be performed is also vital during initial resuscitation. Endoscopic therapy should ideally be performed within 24 hours of presentation after initial stabilization with crystalloids and blood products. Intravenous proton pump inhibitors are the mainstay in the initial management of upper GI bleeding from a non-variceal etiology, and they should be administered in the acute setting to decrease the probability of high-risk stigmata seen during endoscopy. Pro-kinetic agents can be given 30 minutes to an hour before endoscopy and may aid in the diagnosis of UGIB. There are 3 broad categories of endoscopic management for UGIB: injection, thermal, and mechanical. Each endoscopic method can be used alone or in combination with others; however, the injection technique with epinephrine should always be used in conjunction with another method to increase the success of achieving hemostasis. In this review article, we will review the steps of triage and initial resuscitation in UGIB, causes of UGIB and their respective management, several endoscopic techniques and their effectiveness, and prognosis with a primary focus limited to non-variceal bleeding.

Exodontia of third molars in a single surgery using conscious sedation in an anxious patient: case report

The conscious sedation performed by inhaling nitrous oxide gas (N2O) associated with oxygen gas (O2) provides an ideal analgesic and anxiolytic effect for patients who are insecure and anxious to undergo dental procedures. The aim of the present study is to report a clinical case of a single surgery to extract teeth 18, 28, 38, and 48 in an odontophobic patient who undergoes anxiety by using conscious sedation through the inhalation of nitrous oxide gas diluted in oxygen gas. The patient achieved a state of deep relaxation during sedation, with a decrease in his initial heart rate, high oxygen saturation, and low intraoperative bleeding. The authors concluded that conscious sedation using nitrous oxide is an important ally in oral surgeries for anxious patients.

Meta-analysis of clinical efficacy and safety of transanal endoscopic microsurgery and endoscopic submucosal dissection in the treatment of rectal tumors.

The aim of the article was to systematically evaluate the clinical efficacy and safety of transanal endoscopic microsurgery (TEM) and endoscopic submucosal dissection (ESD) in the treatment of rectal tumors. Control studies were conducted on cases included in the electronic databases Medline, Embase, Cochrane Library, and CNKI. Patients with colorectal tumors were included in the TEM and ESD groups for treatment, with the main indicators being R0 resection rate, postoperative perforation and bleeding incidence, and tumor recurrence rate. The meta-analysis was carried out using RevMan 5.3 software. A total of 10 studies were included, with 736 patients. The analysis showed that for the recurrence rate in the TEM group compared to ESD, OR = 1.23, 95% CI = 0.56-2.72, p = 0.60; for the R0 resection rate between the TEM group and ESD group, OR = 1.35, 95% CI = 0.82-2.22, p = 0.24; for the incidence of perforation in the TEM and ESD groups, OR = 0.59, 95% CI = 0.25-1.40, p = 0.23. The inter-group comparison of these three items was statistically significant. Compared with the ESD group, the hospitalization time and the incidence of bleeding of the TEM group were both lower, with SD = 0.48, 95% CI = 0.26-0.69, p < 0.001 and OR = 0.35, 95% CI = 0.13-0.92, p = 0.03. The differences were statistically significant. Both TEM and ESD endoscopic treatment techniques can achieve a higher R0 resection rate and lower risk of tumor recurrence in the treatment of colorectal tumors. However, TEM may have higher surgical safety than ESD technology, and can shorten postoperative hospitalization time and lower postoperative bleeding rate.

Ischaemic and haemorrhagic risk distribution in real-life patients with acute coronary syndromes

Background Effective treatment of non-ST-segment elevation acute coronary syndromes (NSTEACS) requires careful assessment of both ischaemic and bleeding risks. We aimed to analyse risk distribution and evaluate antiplatelet prescription behaviours in real-life settings. Methods Data from 1100 NSTEACS patients in Buenos Aires, Argentina, from the Buenos Aires I Registry, with a 15-month follow-up, were analysed. In-hospital and 6-month GRACE scores, CRUSADE, and Precise DAPT scores were calculated. Results The mean age was 65.4 ± 11.5 years with a majority being male (77.2%). In-hospital mortality was 2.7%, primarily due to cardiovascular causes (1.8%). Bleeding events occurred in 20.9% of patients, with 4.9% classified as ≥ BARC 3. Predominance of low bleeding (71.3%) and ischaemic (55.8%) risks on admission was observed. At 6 months, the low-risk Precise category (70.9%) and GRACE (44.1%) categories prevailed. Linear correlation analysis showed a moderately positive correlation (r = 0.61, p < .05) between ischaemic–haemorrhagic risks. Regarding the prescription of antiplatelet agents, in the low ischaemic–haemorrhagic risk group, there was a predominance of aspirin + clopidogrel (41.2%) over other high-potency antiplatelet regimens (aspirin + ticagrelor or prasugrel). In the low ischaemic and high haemorrhagic risk group, aspirin and clopidogrel were also predominant (58%). Conclusions Our analysis underscores the significant relationship between ischaemic and haemorrhagic risks during NSTEACS hospitalisation. Despite the majority of patients falling into the low-intermediate risk category, the prescription of P2Y12 inhibitors in real-life settings does not consistently align with these risks.

Management of edoxaban therapy in patients undergoing emergency/urgent procedures: a subanalysis of the global, prospective, observational, multinational EMIT-AF/VTE programme

Abstract Background Physicians are often unable to follow recommendations for preprocedural oral anticoagulant interruption before emergency/urgent (unplanned) procedures, which may lead to a higher incidence of adverse outcomes in these patients compared with those who undergo planned procedures. The Global EMIT-AF/VTE programme found low bleeding and thromboembolic event rates for patients receiving edoxaban who underwent diagnostic or therapeutic procedures. However, edoxaban management and clinical outcomes may differ among the subgroup of patients with emergency/urgent procedures. Purpose To describe periprocedural edoxaban management and clinical outcomes for patients in the EMIT-AF/VTE programme who underwent emergency/urgent procedures. Methods In this subanalysis, only physician-reported unplanned (emergency/urgent) procedures were included, of which dental and dermatological procedures were excluded. Only a patient’s first emergency procedure was included, with the exception of 3 patients having 2 procedures on the same day (in these cases the 2 procedures were combined). Procedure bleeding risk was classified according to EHRA criteria, and baseline characteristics and edoxaban interruption data were collected. Clinical event and procedure dates were compared to determine whether they were related. Results Among 156 patients undergoing emergency/urgent procedures, the mean ± standard deviation age at baseline was 74.5 ± 8.7 years, and the CHA2DS2-VASc score was 3.8 ± 1.6. Medical histories of hypertension and dyslipidaemia were reported in 84.0% and 40.4% of patients, respectively; approximately one-quarter of patients had diabetes mellitus (26.9%) or creatinine clearance ≤50 mL/min (24.4%). The most common procedure types were vascular access and transcatheter diagnostics/interventions (34.6%) and gastroenterological procedures (27.6%). Procedures were more often EHRA-classified as minor (35.9%) or low (35.3%) vs high risk (20.5%). Preprocedure edoxaban interruption rates ranged from 39.3%–50.9% across risk groups, with more than half of the procedures being performed with edoxaban interruption (53%–66%; Figure). By 20 days postprocedure, edoxaban therapy was resumed in approximately 86% and 88% of patients with minor- or low-risk procedures vs 70% with high-risk procedures. Overall, 33 clinical events were recorded, of which 18 (54.5%) preceded a procedure (Table). Five bleeding events and one thrombotic event occurred after and were caused by the procedure. Conclusions Edoxaban resumption was protracted after high- vs minor- or low-risk procedures. Bleeding and thrombotic events resulting from a procedure occurred in &amp;lt;4% of patients, indicating that postprocedure edoxaban therapy can be effectively tailored to optimise clinical outcomes.FigureTable

COMPARISON BETWEEN DIFFERENT TRANSRADIAL ARTERY HEMOSTASIS PROTOCOLS IN LIGURIAN CARDIOLOGIES

Abstract Background Transradial artery access (TRA) for coronary angiography and percutaneous coronary intervention is associated with lower bleeding and vascular complications than transfemoral artery access. In our hospital, TRA is widely used and hemostasis is usually achieved using TRBand device. We used to remove the device in about 10 hours according to our protocol. Aims The aim of this study is to describe and compare different TRA hemostasis protocols in order to understand if a shorter protocol could be more effective. Methods This is an observational study performed in all Hospitals of our region (Liguria). All Cardiology Departments were included in this analysis. We requested to all to self–refer: a) which radial hemostasis device was used; b) which deflation protocol (DP) was used. c) If they usually report and analyze adverse events. Adverse events are described as: bleeding, hematoma, ecchymosis, skin damage, local infection, pseudoaneurysm, or artery occlusion. RESULTS In Liguria there are 9 Cardiology Departments with Cath Lab (CL); 8 of them accepted to participate. All the Cath Labs use the TRBAND device but the deflation protocols are very different. 5 Cath Labs follows the DP suggested by the manufacturer. Only 2 CL adopted different DP if and higher dose of heparin was administered. Only one report bleedings or any delete in the DP. None analyze periodically the incidence of adverse events. Conclusions There are different methods to achieve radial hemostasis furthermore with the same device different deflating protocols are used. Further studies are necessary to evaluate the best DP. Regular audits must be strongly suggested in all Cardiology Departments in order to monitorate and improve the adverse events.

DISCONTINUING DAPT: NOT JUST A MATTER OF SCORES BUT OF INTEGRATED EVALUATION? A KEY ROLE OF IMAGING IN A COMPLEX SCENARIO

Abstract The duration of the dual antiplatelet therapy (DAPT) is a widely debated topic within the scientific community. The latest guidelines on acute coronary syndromes have supported the possibility of different therapeutic approaches tailored to patient characteristics. However, the clinical cardiologist‘s decisions are not always based on certain principles. The following case report is a practical example. Discussion: A 31–years–old man came to our attention after a resuscitated cardiac arrest due to ventricular fibrillation during a motorcycle race. His history was characterized by a previous acute myocardial infarction at the age of thirteen due to a traumatic dissection of the proximal left anterior descending (LAD) coronary artery and ascending aorta treated conservatively, with residual transmural necrosis of the mid and subendocardial anterior wall on cardiac MRI. At the admission, ECG showed ST–segment elevation in the anterior leads. Coronary angiography revealed occlusion of the proximal LAD coronary artery, treated with drug–eluting stent (ONYX 5.0 mm), with evidence of dissection and aneurysmal wall of that segment. The patient started a DAPT with aspirin and prasugrel. At discharge, echocardiogram evidenced a moderate left ventricular dysfunction (ejection fraction 34%) with signs of anterior and apical necrosis. Later, the patient was admitted for a subcutaneous defibrillator implantation, due to persistent moderate ventricular dysfunction. One year after revascularization, a lifelong DAPT strategy with downgrading to clopidogrel was considered the best choice for the following considerations: the young age of the patient, the low bleeding risk (PRECISE DAPT score 8), a not elevated DAPT score (value 2), the revascularization in the aneurysmal segment without an appropriate stent apposition (due to absence of a right sizing) and the previous dissection with sign of partial thrombosis at coronary CT. Conclusions: The anatomical complexity of angioplasty procedures and the delicate balance between ischemic and thrombotic risks have led to continuously evolving therapeutic strategies. The clinical scores currently available cannot often account for complex coronary anatomy. Thus, it‘s essential to consider a personalized approach, individualized on clinical and imaging characteristics, that encompasses ischemic and bleeding risk and procedural data for the appropriate treatment for each patient.

P2Y12 Inhibitor Monotherapy After Short-Term Dual Antiplatelet Therapy in Acute Coronary Syndrome

Recent studies have shown similar safety and efficacy of short-term dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor (P2Y12i) monotherapy when compared with standard DAPT. However, the optimal DAPT duration and regimen in acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention is still unclear. Online databases were searched for randomized controlled trials evaluating P2Y12i monotherapy after short DAPT (≤3 months) versus standard DAPT (≥12 months) in ACS patients. The outcomes of interest were all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, target-vessel revascularization, and major bleeding. Random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Six randomized controlled trials with a total of 23,884 patients (n = 11,904 P2Y12i monotherapy, n = 11,980 standard DAPT) were included. Compared with standard DAPT, P2Y12i monotherapy after short DAPT was associated with similar odds of all-cause death (OR 0.86, 95% CI 0.65 to 1.12, p = 0.26) and cardiovascular death (OR 0.75, 95% CI 0.43 to 1.29, p = 0.29) at 1 year. Similarly, there were no significant differences in rates of myocardial infarction (OR 1.09, 0.83 to 1.43, p = 0.53), stent thrombosis (OR 1.09, 95% CI 0.71 to 1.67, p = 0.70) and target-vessel revascularization (OR 0.81, 95% CI 0.65 to 1.01, p = 0.07) between the P2Y12i monotherapy and standard DAPT arms. The P2Y12i monotherapy group had significantly lower major bleeding (OR 0.49, 95% CI 0.38 to 0.64, p < 0.001) when compared with standard DAPT. In conclusion, in patients with ACS who underwent percutaneous coronary intervention, P2Y12i monotherapy after short DAPT significantly reduces bleeding without increasing ischemic risk when compared with standard DAPT therapy.

Perioperative, Oncological, and Functional Outcomes Between Robot-Assisted Laparoscopic Prostatectomy and Open Radical Retropubic Prostatectomy: A Randomized Clinical Trial.

Limited high-quality studies have compared robot-assisted laparoscopic prostatectomy (RALP) vs open retropubic radical prostatectomy. We sought to compare their postoperative outcomes in a randomized setting. In a single center, 354 men with newly diagnosed prostate cancer were assessed for eligibility; 342 were randomized (1:1). The primary outcome was 90-day complication rates. Functional outcomes and quality of life were assessed over 18 months, and oncological outcomes, biochemical recurrence-free survival, and additional treatment over 36 months. From 2014 to 18, 327 patients underwent surgery (retropubic radical prostatectomy = 156, RALP = 171). Complications occurred in 27 (17.3%) vs 19 (11.1%; P = .107). Patients undergoing RALP experienced lower median bleeding (250.0 vs 719.5 mL; P < .001) and shorter hospitalization time. Urinary EPIC (Expanded Prostate Cancer Index Composite) median scores were better for RALP over 18 months, with higher continence rate at 3 months (80.5% vs 64.7%; P = .002), 6 months (90.1% vs 81.6%; P = .036) and 18 months (95.4% vs 78.8%; P < .001). Sexual EPIC and Sexual Health Inventory for Men median scores were higher with RALP up to 12 months, while the potency rate was superior at 3 months (23.9% vs 5.3%; P = .001) and 6 months (30.6% vs 6.9%; P < .001). Quality of life over the 18 months and oncological outcomes over 36 months were not significantly different between arms. Complications at 90 days were similar. RALP showed superior sexual outcomes at 1 year, improved urinary outcomes at 18 months, and comparable oncological outcomes at 36 months. Prospective Analysis of Robot-Assisted Surgery; NCT02292914. https://clinicaltrials.gov/ct2/show/NCT02292914?cond=NCT02292914&draw=2&rank=1.

Effectiveness and safety of half-dose thrombolysis in intermediate-high risk pulmonary embolism: a single centre experience

Abstract Funding Acknowledgements None. Introduction According to current guidelines, full-dose systemic thrombolysis for pulmonary embolism (PE) is limited to patients either classified as high risk or presenting intermediate risk with hemodynamically instability. As evidenced by recent clinical trials, "low" half-dose (50 mg) tissue plasminogen activator (HDrtPA) appears to offer a safe, effective alternative with a low bleeding risk, especially if catheter directed therapies are not available. Purpose we aimed to evaluate if HDrtPA in intermediate-high risk PE could improve right ventricular (RV)-arterial coupling by means of TAPSE/PAPs ratio, right ventricular basal dimensions in 4 chambers (RVD1), and tricuspid velocity (TV) between admission and discharge, exploring eventual associated bleeding risk. Methods we retrospectively analized 90 intermediate-high risk PE patients consecutively admitted to our intensive cardiac care unit between January 2016 and May 2023. Diagnosis was achieved by computed tomography in all cases. All patients underwent echocardiographic assessment upon admission and at discharge along with baseline lab values. HDrtPA patients (Group A, n=28) received low-dose thrombolytic therapy (0,6 mg/kg maximum 50 mg in 1 hour) combined with unfractionated heparin. Standard anticoagulation patients (Group B) included patients exclusively treated with parenteral anticoagulants. Primary endpoint was echocardiographic improvement of RV-arterial coupling (TAPSE/PAPS), and of pulmonary pressures (tricuspid velocity, TV) and right ventricular basal dimension (RVD1) between admission and dis-charge in the two treatment arms. To perform this analysis, linear regression models with Inverse Probability Weighting (IPW) propensity scores were used. Secondary endpoint was presence of mayor or minor bleeding between groups, and a descriptive analysis of mortality due to paucity of events. Results in the whole population mean age was 73.48 ± 12.49 (mean ± sd) and n=43 (47.8%) were males. Between admission and discharge, group A (HDrtPA) had an improvement of TAPSE/PAPs (+0.16, p=0.05, CI 95%: -0.002; 0.325), of RVD1 (-6.00 mm, p &amp;lt;0.01, CI 95%: -2.59; 9.41). Reduction of TV values (-0.45 m/s, p=0.108, CI 95%: -1.02; 0.10) was not statistically significant at IPW propensity score, but deserves further investigations. No significant increase of major bleedings were recorded between two groups (Group A: 1/28 3.5%, Group B: 0/52 0%) with an acceptable number of minor, non fatal bleedings (Group A: 7/28: 25%, Group B 1/62 1.6%). Death occurred in 3 patients in group A (10%) and 1 patient in group B (1.6%). Conclusion half dose of tissue plasminogen activator (HDrtPA) offer a promising alternative to anticoagulation alone therapy in selected patients with high-intermediate risk pulmonary embolism. In our experience, this approach seems to acutely improve RV-arterial coupling and right ventricular dimensions, without an increase of major bleeding risk.

Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant targets.

Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed. To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, P = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, P = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, P = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, P = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, P = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, P = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses. These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.

Comparing clinical outcomes of vitamin K antagonists vs non-vitamin K antagonists in anticoagulant therapy for mesenteric venous thrombosis

ObjectiveNon-vitamin K antagonist oral anticoagulants have shown similar efficacy and lower bleeding rates than vitamin K antagonists for venous thromboembolism. However, this has not been proven in mesenteric vein thrombosis. This study aimed to compare the clinical outcomes of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants. MethodsBetween January 2014 and July 2022, mesenteric vein thrombosis was diagnosed on computed tomography in 225 patients in a tertiary hospital. Among them, a total of 44 patients who underwent long-term anticoagulation therapy over 3 months were enrolled in this study. Patients were divided into two groups based on the anticoagulant used: vitamin K antagonists (Group 1, n = 21) and non-vitamin K antagonist oral anticoagulants (Group 2, n = 23). The efficacy outcomes were symptom recurrence and thrombus resolution on follow-up computed tomography, and the safety outcome was bleeding complications. ResultsThe median age of the patients was 56 years (range, 46-68 years), and 52% were men. The most common risk factors were unprovoked intra-abdominal infections (30%). The median duration of anticoagulation therapy was 13 months (20 months in Group 1 vs 6 months in Group 2; P = .076). Of the 44 patients, 17 (39%) received the standard treatment. The median follow-up period was longer in Group 1 than in Group 2 (57 vs 28 months; P = .048). No recurrence of mesenteric vein thrombosis-related symptoms were observed in either group. The median duration of follow-up computed tomography was 31 months (42 months in Group 1 vs 18 months in Group 2; P = .064). Computed tomography revealed complete thrombus resolution, partial resolution, and no changes in 71%, 19%, and 10%, respectively (P = .075). Regarding bleeding complications, varix bleeding and melena developed in two patients in Group 2, and anticoagulation treatment thereafter ceased. ConclusionsDespite the short follow-up duration in the non-vitamin K antagonist oral anticoagulants group, there was no clinically significant difference in the thrombus resolution rate or bleeding complications when compared with the vitamin K antagonists group. Although research on the long-term effects of non-vitamin K antagonist oral anticoagulants in patients is limited, non-vitamin K antagonist oral anticoagulants can be considered an alternative to conventional treatments.

Left Atrial Appendage Occlusion in Patients With Anticoagulation Failure vs Anticoagulation Contraindication

BackgroundLeft atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO. ObjectivesThis study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data. MethodsThe international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores. ResultsAnalysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT. ConclusionsLAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT.

Intermediate molecular weight–fucosylated chondroitin sulfate from sea cucumber Cucumaria frondosa is a promising anticoagulant targeting intrinsic factor IXa

Thromboembolic diseases pose a serious risk to human health worldwide. Fucosylated chondroitin sulfate (FCS) is reported to have good anticoagulant activity with a low bleeding risk. Molecular weight plays a significant role in the anticoagulant activity of FCS, and FCS smaller than octasaccharide in size has no anticoagulant activity. Therefore, identifying the best candidate for developing novel anticoagulant FCS drugs is crucial. Herein, native FCS was isolated from sea cucumber Cucumaria frondosa (FCScf) and depolymerized into a series of lower molecular weights (FCScfs). A comprehensive assessment of the in vitro anticoagulant activity and in vivo bleeding risk of FCScfs with different molecule weights demonstrated that 10 kDa FCScf (FCScf-10 K) had a greater intrinsic anticoagulant activity than low molecular weight heparin (LMWH) without any bleeding risk. Using molecular modeling combined with experimental validation, we revealed that FCScf-10 K can specifically inhibit the formation of the Xase complex by binding the negatively charged sulfate group of FCScf-10 K to the positively charged side chain of arginine residues on the specific surface of factor IXa. Thus, these data demonstrate that the intermediate molecular weight FCScf-10 K is a promising candidate for the development of novel anticoagulant drugs.

Does Celecoxib Prescription for Pain Management Affect Post-tonsillectomy Hemorrhage Requiring Surgery? A Retrospective Observational Cohort Study.

Adenotonsillectomy and tonsillectomy (referred to as tonsillectomy hereafter) are common pediatric surgeries. Postoperative complications include hemorrhage requiring surgery (2 to 3% of cases) and pain. Although nonsteroidal anti-inflammatory drugs are commonly administered for postsurgical pain, controversy exists regarding bleeding risk with cyclooxygenase-1 inhibition and associated platelet dysfunction. Preliminary evidence suggests selective cyclooxygenase-2 inhibitors, for example celecoxib, effectively manage pain without adverse events including bleeding. Given the paucity of data for routine celecoxib use after tonsillectomy, this study was designed to investigate the association between postoperative celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery using chart-review data from the Children's Hospital of Eastern Ontario. After ethics approval, a retrospective single-center observational cohort study was performed in children less than 18 yr of age undergoing tonsillectomy from January 2007 to December 2017. Cases of adenoidectomy alone were excluded due to low bleed rates. The primary outcome was the proportion of patients with post-tonsillectomy hemorrhage requiring surgery. The association between a celecoxib prescription and post-tonsillectomy hemorrhage requiring surgery was estimated using inverse probability of treatment weighting based on propensity scores and using generalized estimating equations to accommodate clustering by surgeon. An initial patient cohort of 6,468 was identified, and 5,846 children with complete data were included in analyses. Median (interquartile range) age was 6.10 (4.40, 9.00) yr, and 46% were female. In the cohort, 28.1% (n = 1,644) were prescribed celecoxib. Among the 4,996 tonsillectomy patients, 1.7% (n = 86) experienced post-tonsillectomy hemorrhage requiring surgery. The proportion with post-tonsillectomy hemorrhage requiring surgery among patients who had a tonsillectomy and were or were not prescribed celecoxib was 1.94% (30 of 1,548; 95% CI, 1.36 to 2.75) and 1.62% (56 of 3,448; 95% CI, 1.25 to 2.10), respectively. Modeling did not identify an association between celecoxib prescription and increased odds of post-tonsillectomy hemorrhage requiring surgery (odds ratio = 1.4; 95% CI, 0.85 to 2.31; P = 0.20). Celecoxib does not significantly increase the odds of post-tonsillectomy hemorrhage requiring surgery, after adjusting for covariates. This large pediatric cohort study of celecoxib administered after tonsillectomy provides compelling evidence for safety but requires confirmation with a multisite randomized controlled trial.

Screening for exclusion of high-risk bleeding features of esophageal varices in cirrhosis through CT and MRI

Background & aimEsophageal varices (EV) screening guidelines have evolved with improved risk stratification to avoid unnecessary esophagogastroduodenoscopy (EGD) in individuals with low bleeding risks. However, uncertainties persist in the recommendations for certain patient groups, particularly those with hepatocellular carcinoma (HCC) and/or receiving non-selective beta-blockers (NSBB) without prior endoscopy. This study assessed the efficacy of imaging in ruling out EVs and their high-risk features associated with bleeding in patients with cirrhosis and with HCC. We also evaluated the impact of NSBB on the detection of these characteristics. MethodsA total of 119 patients undergoing EGD with CT and/or MRI within 90 days of the procedure were included. 87 patients had HCC. A new imaging grading system was developed utilizing the size of EVs and the extent of their protrusion into the esophagus lumen. The negative predictive value (NPV) of EVimaging(−) versus EVimaging (+) (grades 1–3) in ruling out the presence of EV and/or high-risk features by EGD was calculated. The predictive performance of imaging was determined by logistic regression. ResultsThe NPV of imaging for detecting EV and high-risk features was 81 % and 92 %, respectively. Among HCC patients, the NPV for EV and high-risk features was 80 % and 64 %, respectively. Being on NSBB didn't statistically impact the imaging detection of EV. Imaging was a better predictor of high-risk EGD findings than Child-Turcotte-Pugh scores. ConclusionsOur results suggest that imaging can effectively rule out the presence of EV and high-risk features during EGD, even in patients with HCC and/or receiving NSBB.

Evaluation of Apixaban Use in Patients With Advanced Kidney Disease.

Background: Current guidelines and literature suggest apixaban may be used in patients with severe kidney disease and atrial fibrillation (AF) for stroke and systemic embolism risk reduction (SSE) or patients with acute venous thromboembolism (VTE). Limited data is available for long-term safety and efficacy outcomes in this patient population. Objective: Evaluate the use of apixaban for AF or VTE in patients with advanced kidney disease. Methods: This single-center, retrospective, Investigational Review Board approved study evaluated patients ≥18 years of age with severe kidney disease on apixaban therapy for VTE or AF from March 1, 2018, to December 31, 2020. The primary outcome was major bleeding from apixaban initiation/continuation until 12 months after discharge. The secondary outcomes included a composite bleed (major bleeding, clinically relevant non-major bleeding, and minor bleeding), the occurrence of VTE or SSE, and death during hospitalization from any cause other than bleeding. Results: Overall, 156 patients met inclusion criteria. Six patients experienced major bleeding (3.8%). Composite bleeding occurred in 16 patients (10.3%); no patients had SSE or VTE, and 4 patients died from causes other than bleeding (2.6%). Limitations included the small sample size and retrospective nature of the study. Conclusion: This study demonstrated that patients with advanced chronic kidney disease on apixaban for AF or VTE had low major bleeding and similar overall bleeding rates compared with previously published literature. When considering the use of apixaban in this population, risks and benefits should be weighed in addition to the consideration of FDA-label dosing guidance.

Assessment of Effectiveness and Safety of Aspiration-Assisted Nephrostomic Access Sheaths in PCNL and Intrarenal Pressures Evaluation: A Systematic Review of the Literature.

Background: Different suction-assisted nephrostomic sheaths have been developed for percutaneous nephrolithotomy (PCNL). Objectives: (1) To examine PCNL techniques performed with different aspiration-assisted sheaths (Clear Petra® sheath, Superperc, SuperminiPCNL, and a miniPCNL patented sheath), with specific regard to effectiveness and safety outcomes in adult and paediatric patients; (2) to extrapolate intrarenal pressure (IRP) data during these procedures. Methods: A systematic literature search was performed in accordance with PRISMA guidelines. Relevant articles up to 8 February 2024 were included. Results: Twenty-five studies were selected, thirteen retrospective and twelve prospective. The use of four different aspirating sheaths for miniPCNL was reported: Clear Petra® sheath, Superperc, SuperminiPCNL, and a miniPCNL patented sheath. Stone free rates (SFRs) across techniques ranged from 71.3% to 100%, and complication rates from 1.5% to 38.9%. Infectious complication rates varied from 0 to 27.8% and bleeding complication rates from 0 to 8.9%. Most complications were low grade ones. The trend among studies comparing aspiration- and non-aspiration-assisted miniPCNL was towards equivalent or better SFRs and lower overall infectious and bleeding complication rates in suction techniques. Operation time was consistently lower in suction procedures, with a mean shortening of the procedural time of 19 min. Seven studies reported IRP values during suction miniPCNL. Two studies reported satisfactory SFRs and adequate safety profiles in paediatric patient cohorts. Conclusions: MiniPCNL with aspirating sheaths appears to be safe and effective in both adult and paediatric patients. A trend towards a reduction of overall infectious and bleeding complications with respect to non-suction procedures is evident, with comparable or better SFRs and consistently shorter operative times. The IRP profile seems to be safe with the aid of aspirating sheaths. However, high quality evidence on this topic is still lacking.

Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect.

Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.

In-hospital outcomes with extracorporeal membrane oxygenation alone versus combined with percutaneous left ventricular assist device

BackgroundVeno-arterial extracorporeal membrane oxygenation (ECMO) is associated with increased afterload and hindered myocardial recovery. Adding a percutaneous left ventricular assist device (pLVAD) to ECMO is one strategy to unload the left ventricle. We evaluated in-hospital outcomes in cardiogenic shock patients treated with ECMO alone versus ECMO plus pLVAD. MethodsWe conducted a retrospective study using the National Inpatient Sample database from 2011 to 2019. Logistic regression analysis was performed to adjust for covariates. Results20,171 patients were included. 16,064 (79.6 %) patients received ECMO alone and 4107 (20.4 %) patients received ECMO plus pLVAD. The ECMO plus pLVAD group had higher rates of mortality, stroke, acute kidney injury, pericardial complications, and vascular complications. After adjusting for covariates, combined therapy was associated with higher rates of mortality (OR 1.2; 95 % CI [1.1–1.3]) and stroke (OR 1.3; 95 % CI [1.2–1.5]), however lower bleeding (OR 0.7; 95 % CI [0.68–0.81]) (p < 0.001 for all). After adjusting for covariates, a subgroup analysis of 5019 patients with acute coronary syndrome cardiogenic shock (ACS-CS) demonstrated higher rates of mortality (OR 1.3; 95 % CI [1.2–1.5]) and stroke (OR 1.7; 95 % CI [1.4–2.1]; p < 0.001 for all) with combined therapy, however similar rates of bleeding compared to ECMO alone (OR 0.95; 95 % CI [0.8–1.1]; p = 0.54). ConclusionsIn the overall group, ECMO plus pLVAD was associated with increased mortality and stroke, however decreased bleeding. In a sub-group of ACS-CS, ECMO plus pLVAD was associated with increased mortality and stroke, however similar rates of bleeding compared to ECMO alone.