Exploring ligands that target von Willebrand factor selectively under oxidizing conditions through docking and molecular dynamics simulations.

The blood protein von Willebrand factor (VWF) is a large multimeric protein that, when activated, binds to blood platelets, tethering them to the site of vascular injury and initiating blood coagulation. This process is critical for the normal hemostatic response, but especially under inflammatory conditions, it is thought to be a major player in pathological thrombus formation. For this reason, VWF has been the target for the development of anti-thrombotic therapeutics. However, it is challenging to prevent pathological thrombus formation while still allowing normal physiological blood coagulation, as currently available anti-thrombotic therapeutics are known to cause unwanted bleeding, in particular intracranial hemorrhage. This work explores the possibility of inhibiting VWF selectively under the inflammatory conditions present during pathological thrombus formation. In particular, the A2 domain of VWF is known to inhibit the neighboring A1 domain from binding to the platelet surface receptor GpIbα, and this auto-inhibitory mechanism has been shown to be removed by oxidizing agents released during inflammation. Hence, finding drug molecules that bind at the interface between A1 and A2 only under oxidizing conditions could restore such an auto-inhibitory mechanism. Here, by using a combination of computational docking, molecular dynamics simulations, and free energy perturbation calculations, a ligand from the ZINC15 database was identified that binds at the A1A2 interface, with the interaction being stronger under oxidizing conditions. The results provide a framework for the discovery of drug molecules that bind to a protein selectively in the presence of inflammatory conditions.

A systematic critical appraisal of clinical practice guidelines of antithrombotic agents in gastrointestinal endoscopy using the AGREE II tool.

BACKGROUND AND AIM: The quality of clinical practice guidelines (CPGs) for the management of antithrombotic agents in patients undergoing gastrointestinal (GI) endoscopy has not been systematically appraised. The goal of this study was to evaluate the methodological quality of CPGs for the management of antithrombotic agents in periendoscopic period published within last 6 years. METHODS: A systematic search of PubMed and Embase databases was performed to identify eligible CPGs published between January 1, 2016, and April 14, 2022, addressing the management of antithrombotic agents in the periendoscopic period. The quality of the CPG was independently assessed by six reviewers using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Domain scores were considered of sufficient quality when > 60% and of good quality when > 80%. RESULTS: The search yielded 343 citations, of which seven CPGs published by the gastroenterology associations in Asia (n = 3), Europe (n = 2), and North America (n = 2) were included for the critical appraisal. The overall median score for the AGREE II domains was 93% (interquartile range [IQR] 11%) for scope and purpose, 79% (IQR 61%) for stakeholder involvement, 79% (IQR 36%) for rigor of development, 100% (IQR 14%) for clarity of presentation, 32% (IQR 36%) for applicability, 93% (IQR 29%) for editorial independence, and 86% (IQR 29%) for overall assessment. CONCLUSIONS: The findings show that the overall methodological quality of the CPGs for the management of antithrombotic agents in the periendoscopic period varies across the domains. There is significant scope for improvement in the methodological rigor and applicability of CPGs.

Oral factor Xa inhibitor underutilization following lower extremity peripheral vascular intervention.

OBJECTIVE: Patients undergoing peripheral vascular intervention (PVI) (ie, endovascular revascularization) for symptomatic lower extremity peripheral artery disease remain at high risk for major adverse limb and cardiovascular events. High-quality evidence demonstrates the addition of a low-dose oral factor Xa inhibitor to single antiplatelet therapy, termed dual pathway inhibition (DPI), reduces the incidence of major adverse events in this population. This study aims to describe the longitudinal trends in factor Xa inhibitor initiation after PVI, identify patient and procedural characteristics associated with factor Xa inhibitor use, and describe temporal trends in antithrombic therapy post-PVI before vs after VOYAGER PAD. METHODS: This retrospective cross-sectional study was performed using data from the Vascular Quality Initiative PVI registry from January 2018 through June 2022. Multivariate logistic regression was utilized to determine predictors of factor Xa inhibitor initiation following PVI, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 91,569 PVI procedures were deemed potentially eligible for factor Xa inhibitor initiation and were included in this analysis. Overall rates of factor Xa inhibitor initiation after PVI increased from 3.5% in 2018 to 9.1% in 2022 (P < .0001). The strongest positive predictors of factor Xa inhibitor initiation after PVI were non-elective (OR, 4.36; 95% CI, 4.06-4.68; P < .0001) or emergent (OR, 8.20; 95% CI, 7.14-9.41; P < .0001) status. The strongest negative predictor was postoperative dual antiplatelet therapy prescription (OR, 0.20; 95% CI, 0.17-0.23; P < .0001), highlighting significant hesitation about use of DPI after PVI and limited translation of VOYAGER PAD findings into clinical practice. Antiplatelet medications remain the most common antithrombotic regimen after PVI, with almost 70% of subjects discharged on dual antiplatelet therapy and approximately 20% discharged on single antiplatelet therapy. CONCLUSIONS: Factor Xa inhibitor initiation after PVI has increased in recent years, although the absolute rate remains low, and most eligible patients are not prescribed this treatment.

Benefits of laparoscopic liver resection in elderly patients.

BACKGROUND: The indications of laparoscopic liver resection (LLR) have expanded to high-risk patients, such as elderly people. However, to date, little evidence has been established of the safety and feasibility of LLR in elderly patients. The short-term outcomes of LLR in elderly patients as compared to non-elderly patients were investigated. METHODS: Data of a total of 297 patients who underwent LLR were reviewed. Among these 297 patients, 181 patients were < 75 years age (non-elderly) and 116 patients were ≥ 75 years age (elderly), and the surgical outcomes were compared between the groups. In addition, we evaluated the risk factors for postoperative morbidity (Clavien-Dindo grade ≥ IIIa) utilizing the preoperative, operative, and postoperative variables RESULTS: The preoperative liver/renal function, frequency of anti-thrombotic drug use, number of comorbidities, and American Society of Anesthesiologists-physical status classification were more unfavorable in elderly patients than in non-elderly patients. No significant inter-group differences were observed in the operation time, blood loss, conversion rate, postoperative morbidity, or 30-day mortality. The 3-year overall survival rate was comparable between the two groups. Multivariate analysis identified anti-thrombotic drug use, operation time > 7 h, and peak serum total bilirubin > 2 mg/dl within postoperative day 3 as independent risk factors for Clavien-Dindo ≥ IIIa postoperative morbidity (P = 0.016, P < 0.001, and P = 0.001, respectively). CONCLUSIONS: LLR in elderly patients may provide comparable short-term outcomes to those in non-elderly patients.

Systematic review on traumatic intracranial haemorrhage in patients on anti-thrombotic medications; haemorrhage progression, thrombosis, and anti-thrombotic recommencement.

A large number of patients who sustain a traumatic intracranial haemorrhage (tICH) are taking anti-thrombotic (AT) medications at the time of injury. These are stopped acutely, but there is uncertainty about safe timing for recommencement. This review aimed to understand the rate of new/progressive haemorrhage, thrombosis, and death in tICH patients on ATs and the rate and timing of AT recommencement. A systematic review of OVID Medline and EMBASE from 2000 to 2021 including adult patients with tICH on ATs with reported outcomes was performed. A total of 59 observational studies (20,421 patients) were included. Most patients were elderly (mean age 74), suffering falls (78%), and had a mild head injury. The mean new/progressive haemorrhage rate during admission was 26%, mostly diagnosed on routine imaging performed within 72 h of injury, with only 8% clinically significant. Thrombotic events were reported in 17 studies; mean rate of 3% during admission, 4-9% at 30 days and 3-11% at 6 months. AT recommencement rate and timing were only reported in six studies and varied widely, with some studies demonstrating reduced thrombotic events and mortality with earlier AT recommencement. Current data is observational and sparse in relation to haemorrhage, thrombosis, and AT recommencement. There is some suggestion that early recommencement, within 7-14 days, may be beneficial but higher quality studies with more consistent data are urgently required.

Application of artificial neural network in daily prediction of bleeding in ICU patients treated with anti-thrombotic therapy.

OBJECTIVES: Anti-thrombotic therapy is the basis of thrombosis prevention and treatment. Bleeding is the main adverse event of anti-thrombosis. Existing laboratory indicators cannot accurately reflect the real-time coagulation function. It is necessary to develop tools to dynamically evaluate the risk and benefits of anti-thrombosis to prescribe accurate anti-thrombotic therapy. METHODS: The prediction model,daily prediction of bleeding risk in ICU patients treated with anti-thrombotic therapy, was built using deep learning algorithm recurrent neural networks, and the model results and performance were compared with clinicians. RESULTS: There was no significant statistical discrepancy in the baseline. ROC curves of the four models in the validation and test set were drawn, respectively. One-layer GRU of the validation set had a larger AUC (0.9462; 95%CI, 0.9147-0.9778). Analysis was conducted in the test set, and the ROC curve showed the superiority of two layers LSTM over one-layer GRU, while the former AUC was 0.8391(95%CI, 0.7786-0.8997). One-layer GRU in the test set possessed a better specificity (sensitivity 0.5942; specificity 0.9300). The Fleiss' k of junior clinicians, senior clinicians, and machine learning classifiers is 0.0984, 0.4562, and 0.8012, respectively. CONCLUSIONS: Recurrent neural networks were first applied for daily prediction of bleeding risk in ICU patients treated with anti-thrombotic therapy. Deep learning classifiers are more reliable and consistent than human classifiers. The machine learning classifier suggested strong reliability. The deep learning algorithm significantly outperformed human classifiers in prediction time.

The medicinal panorama of benzimidazoles and their scaffolds as anticancer and antithrombotic agents: A review.

Nitrogen-containing heterocyclic scaffolds have become a prospective pharmacophore with therapeutic importance due to their biological similarities with natural and synthetic drugs. Among all nitrogen heterocyclic compounds, benzimidazoles and their derivatives are privileged molecules structurally akin to naturally available nucleotides, enabling them to intercommunicate with numerous biopolymers in biological systems. This reason enlightens modern researchers worldwide to assess their potential significance in the context of synthetic and biological chemistry. Therefore, it is crucial to merge the latest data with the prior documentation to apprehend the ongoing situation of the benzimidazole moiety in various therapeutic zones of research. The current work displays that the benzimidazole center is a versatile nucleus that offers the necessary data of synthetic alterations for pre-existing compounds to provide new scaffolds to resist numerous therapeutic sectors, including those associated with anticancer and antithrombosis. Due to the potential significance of benzimidazoles, this review aims to emphasize the latest innovations in synthesizing several other notable benzimidazole substrates and their significant pharmacological prospects for the future, including anticancer and antithrombosis.

Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from the Poecilobdella manillensis Leech.

When Poecilobdella manillensis attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of P. manillensis, but the substance that produces the paralyzing effect in P. manillensis is not known. In this study, we successfully isolated, purified, and identified a serine protease inhibitor containing an antistasin-like domain from the salivary secretions of P. manillensis. This peptide (named poeciguamerin) significantly inhibited elastase activity and slightly inhibited FXIIa and kallikrein activity, but had no effect on FXa, trypsin, or thrombin activity. Furthermore, poeciguamerin exhibited analgesic activity in the foot-licking and tail-withdrawal mouse models and anticoagulant activity in the FeCl3-induced carotid artery thrombosis mouse model. In this study, poeciguamerin was found to be a promising elastase inhibitor with potent analgesic and antithrombotic activity for the inhibition of pain and thrombosis after surgery or in inflammatory conditions.

Direct Oral Anticoagulation Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves: a Retrospective, Real-World Cohort Study.

OBJECTIVE: In this retrospective cohort study of consecutive patients with atrial fibrillation and surgical or transcatheter bioprosthetic valve, we compared the efficacy and safety of direct oral anticoagulants with warfarin. METHODS: Using linked health administrative databases housed at the Institute for Clinical Evaluative Sciences, we identified consecutive patients in Ontario (Canada) 65 years of age or older with AF who underwent bioprosthetic valve replacement between 1 April 2012 and 31 March 2017. We created a time-varying Cox model to examine the relationship between the type of anticoagulant and time to thrombotic or bleeding events after adjustment for baseline risk of thrombosis using the CHA2DS2-VASc score and risk of bleeding using the HAS-BLED scores. We conducted prespecified subgroup analyses according to whether valve implantation was surgical or transcatheter. RESULTS: We identified 2245 eligible patients. The mean age was 79 years, 41% were female, and 39% had transcatheter aortic valve replacement. Risk of death or thrombosis was not different between direct oral anticoagulants and warfarin after adjustment for CHA2DS2-VASc score (hazard ratio [HR] 1.02, 95% confidence interval [CI], 0.83-1.25). Risk of death or bleeding was not different between direct oral anticoagulants and warfarin after adjustment for HAS-BLED score (HR 0.89, 95% CI 0.75-1.07). Subgroup analyses of surgical or transcatheter valves were consistent with overall results. CONCLUSIONS: In a real-world population of patients with atrial fibrillation and bioprosthetic valve replacement, we found no difference between direct oral anticoagulants and warfarin with regard to the risk of thrombosis or bleeding.

Effectiveness and safety of the direct oral anticoagulants in non-triple positive antiphospholipid syndrome without prior arterial thromboembolism.

Thrombotic antiphospholipid syndrome (TAPS) is an autoimmune disorder that manifests with venous thromboembolism (VTE) and/or arterial thromboembolism (ATE) in the presence of persistent antiphospholipid antibodies (aPLs). Recent trials have failed to demonstrate non-inferiority of the direct oral anticoagulants (DOACs) compared to vitamin K antagonists as anticoagulation in TAPS, but there is a subgroup of non-triple positive patients without prior ATE in who only limited data exists. The objective of this study was to assess the effectiveness and safety of DOACs in non-triple positive TAPS without prior ATE. We conducted a retrospective review of all non-triple positive TAPS patients without prior ATE who were anticoagulated with a DOAC at two tertiary care hospitals from January 2010 to July 2020. We assessed outcomes of VTE, ATE, major bleeding, and clinically relevant non-major bleeding (CRNMB). 50 patients were included in the analysis, encompassing 157.2 years of patient follow-up. There were no recurrent VTE, but one patient had a possible arterial thrombosis (0.64 events per 100 patient-years [95% confidence interval (CI 0.16-35.49)] as a transient ischemic attack (TIA) which occurred on reduced dose DOAC. There were no major bleeding events, but two patients had CRNMB (1.27 events per 100 patient-years [95% CI 1.5-46.0]), both as menorrhagia. DOACs were effective and safe as anticoagulation in non-triple positive TAPS patients without prior ATE with a low rate of recurrent thrombosis and bleeding. Larger, prospective controlled studies are required to confirm these findings prior to routine use of DOACs in this subgroup.

A systematic review of randomized controlled trials related to the effects of garlic supplementation on platelet aggregation.

The increment of platelet aggregation factors has been considered a key phenomenon in atherosclerosis. Studies have shown that garlic (Allium sativum) is associated with a reduction in platelet aggregation and thrombosis. Hence, the present systematic review was conducted to evaluate the effect of garlic on platelet aggregation. All randomized controlled trials (RCTs) with keywords related to garlic and platelet aggregation were thoroughly searched in electronic databases including PubMed, Scopus, ISI Web of Science, and Google Scholar up to January 2021. Moreover, the references of all related articles were screened to discover more relevant studies. The quality of each study was reported based on Cochrane Collaboration's tool. In total, 12 studies met the inclusion criteria from 18,235 identified articles (including 595 participants). Most of the studies assessed platelet aggregation in response to different inducers. Of the 12 clinical trials, six studies depicted the beneficial effect of garlic on reducing platelet aggregation. The summary of the quality assessment indicated that most of the studies had high-quality scores. Regarding the small number of RCTs and heterogeneity between studies, it is impossible to make a proper conclusion about the impacts of garlic on platelet aggregation. Therefore, further precise trials with a standard design are necessary to validate the anti-thrombotic effect of garlic.

Factors associated with infrainguinal bypass graft patency at 1-year; a retrospective analysis of a single centre experience.

INTRODUCTION: The aim of this study was to identify factors associated with primary graft patency 1 year following open lower limb revascularisation (LLR) at a tertiary referral vascular service. METHODS: A retrospective analysis of patients undergoing infra-inguinal bypass surgery between January 2016 and May 2017 at a tertiary vascular centre (St Mary's Hospital, London) was performed. Data regarding patient demographics, comorbidities, type of operation and post-operative anti-thrombotic strategy were collected. Quality of run-off score was assessed from pre-operative imaging. RESULTS: Seventy-seven cases were included in the analysis. Overall, the primary patency rate at 1-year was 63.6% (n = 49/77) and the secondary patency rate was 67.5% (n = 52/77). Independent variables with statistically significant inferior patency rates at 1-year were (1) bypasses with below knee targets (p = 0.0096), (2) chronic limb threatening ischaemia indication (p = 0.038), (3) previous ipsilateral revascularisation (p < 0.001) and (4) absence of hypertension history (p = 0.041). There was also a trend towards significance for American Society of Anesthesiologists (ASA) grade (p = 0.06). Independent variables with log-rank test p values of <0.1 were included in a Cox proportional hazards model. The only variable with a statistically significant impact on primary patency rates was previous open or endovascular ipsilateral revascularisation (HR 2.44 (1.04-5.7), p = 0.04). CONCLUSION: At 1-year follow-up, previous ipsilateral revascularisation was the most significant factor in affecting patency rates. Patients in this subgroup should therefore be deemed high-risk, which should be reflected in the informed consent and peri-operative management.

Formulation of Isopropyl Isothiocyanate Loaded Nano Vesicles Delivery Systems: In Vitro Characterization and In Vivo Assessment.

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.

Endovascular therapy for acute ischemic stroke: The importance of blood pressure control, sedation modality and anti-thrombotic management to improve functional outcomes.

Since 2015, endovascular therapy (EVT) following intravenous thrombolysis (IVT) is the gold standard treatment for patients suffering from acute ischemic stroke (AIS) due to an anterior large vessel occlusion (LVO). Despite high recanalization rates, nearly half of successfully treated patients remain dependent at three months. This result underlines that other factors may have a prognostic value, such as blood pressure (BP) management, the sedation modality and anti-thrombotic strategy during and after EVT. Extreme BP variations before and after recanalization are associated with worse outcomes. During EVT, BP variability is strongly associated with worse functional outcomes. Indeed, several studies have highlighted the deleterious impact of BP drops and hypotension duration on functional outcomes and final infarct volume. Interestingly, several studies have shed light on the potential value of an individualized BP management based on several baseline clinical or radiological parameters, such as the collateral status or the circle of Willis conformation. Such approaches are being investigated and could lead to a paradigm shift compared to the one-size-fits-all approach. After EVT, recent evidence suggests that an intensive systolic BP reduction (100-129mmHg) does not reduce the occurrence of intracranial hemorrhage compared to the guideline-recommended systolic BP control (130-185mmHg). Anesthetic management also seems to have a major impact on functional outcome. The latest studies suggest that general anesthesia may be associated with better functional outcomes and faster procedures and may have neuroprotective effects. However, further studies are needed in order to clarify the best anesthetic management for EVT. Finally, new anti-thrombotic treatments are increasingly used during EVT and are currently investigated to increase recanalization rates and improve reperfusion. However, the current literature is scarce regarding the association of IVT, EVT and antiplatelet therapy such as anti-GPIIbIIIa or P2Y12 inhibitors. These strategies raise several issues, such as an increase in intracranial hemorrhage rates.

Pharmacokinetics and pharmacodynamics of intravenous and oral apixaban in horses.

Large vessel and microvascular thrombi are common complications in systemically ill horses contributing to patient morbidity and mortality. Apixaban, an oral factor Xa inhibitor, shows excellent efficacy against stroke and deep vein thrombosis in humans. The purpose of this study was to determine serum apixaban concentrations and anti-factor Xa activity in horses after orally administered apixaban. Five horses received a single dose of intravenous (0.09 mg/kg) and oral (1 mg/kg) apixaban in a cross-over design. Serum apixaban concentrations and anti-Xa activity were measured serially via liquid chromatography-tandem mass spectrometry and a commercial assay, respectively, for 12 hr following oral administration. Apixaban was detected in all horses after both oral and intravenous administration. Oral administration yielded a mean maximum concentration of 60.3 ng/ml (59.4-111 ng/ml), mean time to maximum concentration of 0.5 hr (0.5-2), mean half-life of 6.2 hr (4.6-8.3), and mean oral bioavailability of 10% (3.8-17.4). After oral administration, anti-Xa activity had a strong positive relationship with serum apixaban and was best represented by a dose-response model with the following parameters: E0  = 5.00 ng/ml, EMAX  = 311 ng/mL, EC50  = 267 ng/ml, and n = 1.58. Anti-Xa activity was significantly higher 2 hr post-administration compared with baseline (p = .032). Despite low oral bioavailability, administration of 1 mg/kg oral apixaban, in healthy horses, achieves serum concentrations similar to those reported in humans. Apixaban has potential clinical utility in horses and warrants further investigation.

Redesigning Nature: Ruthenium Flavonoid Complexes with Antitumour, Antimicrobial and Cardioprotective Activities.

Flavonoids are a class of natural polyphenolic compounds sharing a common 2-phenyl-3,4-dihydro-2H-1-benzopyran (flavan) backbone. Typically known for their antioxidant activity, flavonoids are also being investigated regarding antitumour and antimicrobial properties. In this review, we report on the complexation of both natural and synthetic flavonoids with ruthenium as a strategy to modulate the biological activity. The ruthenoflavonoid complexes are divided into three subclasses, according to their most prominent bioactivity: antitumour, antimicrobial, and protection of the cardiovascular system. Whenever possible the activity of the ruthenoflavonoids is compared with that of commercial drugs for a critical assessment of the feasibility of using them in future clinical applications.

Screening of Potential Anti-Thrombotic Ingredients from Salvia miltiorrhiza in Zebrafish and by Molecular Docking.

BACKGROUND: Danshen (DS), the dry root of Salvia miltiorrhiza Bge., has been used in traditional Chinese medicine (TCM) for many years to promote blood circulation and to inhibit thrombosis. However, the active ingredients responsible for the anti-thrombotic effect and the underlying mechanisms are yet to be fully elucidated. METHODS: Molecular docking was used to predict the active ingredients in DS and their potential targets by calculating the scores of docking between DS ingredients and thrombosis-related proteins. Then, a chemical-induced zebrafish thrombosis model was applied to confirm their anti-thrombotic effects. RESULT: The molecular docking results indicated that compared to the control ligand, higher docking scores were observed for several compounds in DS, among which salvianolic acid B (SAB), lithospermic acid (LA), rosmarinic acid (MA), and luteolin-7-O-ß-d-glucoside (LG) could attenuate zebrafish caudal vein thrombosis and recover the decrease in heart red blood cells (RBCs) in a dose-dependent manner. CONCLUSIONS: Our study showed that it is possible to screen the potential active components in natural products by combining the molecular docking method and zebrafish in vivo model.

Appropriate use of anti-thrombotic therapy in patients with atrial fibrillation at single-center experience, Northwest Ethiopia.

BACKGROUND: Atrial fibrillation (AF) is the commonest clinically significant ECG-evidenced sustained cardiac arrhythmia in clinical practice. Disability and mortality attributed to AF is high in low-income regions like sub-Saharan Africa. The risk of stroke/TIA in patients with AF can be significantly reduced with anti-thrombotic therapy. Despite the existing evidence of its benefit, significant percentages of AF patients eligible for anti-thrombotic therapy are undertreated in the region. METHODS: A hospital-based cross-sectional study was conducted to determine the appropriate use of anti-thrombotic therapy in patients with AF between December 1, 2018 and September 30, 2019 at Cardiac Clinic, University of Gondar hospital, Northwest Ethiopia. Consecutive sampling method was used to recruit 210 study subjects. Patients were interviewed to obtain socio-demographic data. Relevant medical history and laboratory parameters were obtained from patients' records. Diagnosis of atrial fibrillation was based on detection of irregular arterial pulse and presence of 'f' waves on 12-lead ECG tracing. Clinical evaluation, echocardiography, chest X-ray and blood chemistry were used to diagnose underlying causes of AF. Data was entered into EPI Info version 4.4.1 and analyzed using SPSS version 20. Bi-variate and multi-variate logistic regression analyses were used to identify associated factors with appropriate use of anti-thrombotic therapy in patients with atrial fibrillation. P-values < 0.05 were used to declare significant association. RESULTS: A total of 210 patients were included in the study. The mean age of patients was 51.29 ± 17.2 years. Two-thirds (145/210) of participants were females. Seventy-four (35%) had valvular AF, while 136/210 (65%) had non-valvular AF. Sixty-six percent (139/210) of study subjects were appropriately treated with anti-thrombotic therapy. Appropriately treated subjects in valvular AF group and non-valvular AF group were 58/74 (78%) and 81/136 (60%) respectively. On multi-variate analysis, 'can afford for regular INR monitoring' (AOR = 2.60 95% CI: 1.10-6.10, P = 0.001) was significantly associated with appropriate use of anti-thrombotic therapy. CONCLUSION: Sixty-six percent of AF patients eligible for anti-thrombotic therapy were appropriately treated. Intervention program to access 'regular INR monitoring' should be practiced to escalate utilization rate of anti-thrombotic therapy (warfarin) in eligible AF patients.

Periodontitis and cardiovascular diseases: Consensus report.

BACKGROUND: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. MATERIAL AND METHODS: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations RESULTS AND CONCLUSIONS: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

Laparoscopic surgery in rectal cancer patients taking anti-thrombotic therapy.

Background: Several previous studies have shown that laparoscopic resection of rectal cancer is a feasible option. However, its safety and efficacy in patients receiving long-term anti-thrombotic therapy (AT) remain unclear.Material and methods: We retrospectively reviewed 364 patients who underwent elective resection for rectal cancer via a laparoscopic approach between 2007 and 2018 in our institute. Patients were classified according to the long-term use of AT. AT was interrupted perioperatively with or without heparin bridging therapy in all anti-thrombotic users. Clinicopathological factors and surgical outcomes were analyzed between patient groups.Results: Thirty-two patients (9%) receiving AT were older and had lower albumin and hemoglobin levels than those not receiving AT (the non-AT group), and were predominantly male. Estimated blood loss and operative time in the AT group (median: 50 mL and 294 min) did not differ from those in the non-AT group (median: 20 mL and 295 min). There were no intergroup differences in the frequencies of other postoperative complications and oncological outcomes.Conclusions: Our results at the very least can support that laparoscopic surgery for rectal cancer is a safe and feasible option for patients taking long-term AT discontinued perioperatively.