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[Abstract] The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

While there is a clear clinical benefit of oral anticoagulation in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision for initiating and continuing anticoagulation is often based on a careful assessment of both thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug–drug and food–drug interactions. Bleeding risk is also not a static “one-off” assessment based on baseline factors but is dynamic, being influenced by aging, incident comorbidities, and drug therapies. In this executive summary of a European and Asia-Pacific Expert Consensus Paper, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with a view to summarizing “best practice” when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, and review established bleeding risk factors and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism, are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

Bleeding is a frequent complication of the management of patients with coronary artery disease (CAD), especially those presenting with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI), and of patients with atrial fibrillation (AF). Randomized trials have shown a risk of major bleeding of 1–8% at 30 days in ACS patients,1–5 and of 2–5% per year in patients with AF treated with oral anticoagulants (OACs).6 Observational studies suggest that bleeding risk is even higher.7 Major bleeding is associated with a subsequent increase in both short- and long-term mortality.7–13 Even minimal bleeding may have prognostic importance because it frequently leads to disruption of antithrombotic therapy.14,15 Several mechanisms have been put forward to explain the relationship between major bleeding and increased mortality ( Figure 1 ). The overlap in risk factors for bleeding and ischaemic events means that patients who are more likely to suffer from bleeding complications of antithrombotic therapy also tend to be at higher risk of thrombotic events.16 Discontinuation of antithrombotic drugs may lead to an increased rate of thrombotic events due to the progressive recovery of platelet function and coagulation activity.17–19 In addition, bleeding may provoke prothrombotic responses beyond those related to discontinuation of antithrombotic drugs.20,21 Clearly, balancing the risks of further bleeding vs. potentially fatal thrombotic events is critical for decisions about if and when to restart antithrombotic therapy after bleeding. Figure 1 Hypothetical mechanisms linking bleeding to thrombotic events and death. Numerous risk factors for bleeding are also risk factors for myocardial infarction, stroke and death (large arrows). VTE, venous thromboembolism. Although several recommendations have been published dealing with the acute management of bleeding in patients treated with antithrombotic drugs,22–24 there is an unmet need for guidance on how to manage antithrombotic therapy after bleeding …

Rationale, aims, and objectives Several novel oral anticoagulants (NOACs) are licensed for atrial fibrillation (AF) treatment in the United Kingdom. We describe the incidence and mortality from ischaemic stroke and major bleeding in non-valvular atrial fibrillation (NVAF) patients in England, including treatment patterns before/following introduction of NOACs, healthcare resource utilization (HRU), and costs post-onset of these events. Method Data were extracted from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics secondary care and Office for National Statistics mortality data. Results Of 42 966 patients with a first AF record between 2011 and 2016, 9143 patients (21.3%) remained without AF (antiplatelets/antithrombotics) treatment post-index diagnosis. The proportion of patients receiving aspirin for ≥3 months post-index declined during the study (50.6%-5.5%), irrespective of CHA2 DS2 -VASc score, while the proportion prescribed NOACs increased (2.0%-70.1%). Rates of ischaemic stroke per 1000 patient-years (95% CI) were 9.4 (3.8-15.0) with NOACs, 10.4 (8.0-12.9) with warfarin, 20.1 (16.4-23.8) with aspirin, 21.3 (5.3-37.2) with other antiplatelets and 43.6 (39.3-47.8) in patients without AF prescription. Major bleeding occurred at a similar rate with different treatments. All-cause mortality rates were 42.8 (31.4-54.3) with NOACs, 46.3 (41.1-51.5) with warfarin, 56.5 (50.5-62.4) with aspirin, 102.2 (76.2-128.3) with other antiplatelets and 412.8 (399.6-426.0) with no AF prescription. Mean annual National Health Service healthcare costs up to 1 year post-index were lowest in patients receiving aspirin plus other antiplatelets without an event (£6152), and highest in patients with an event without AF prescriptions (£17 957). By extrapolation, national AF HRU in the United Kingdom in 2016 was estimated at £8-16 billion annually. Conclusions These data provide temporal insights into AF treatment patterns and outcomes for NVAF patients in England and highlight the need to review higher stroke risk AF patients not receiving antiplatelet/antithrombotic prescriptions.

Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25–300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6–5.9) g/dL (7.8 vs. 12.7 g/dL, P

Background Atrial fibrillation (AF) is a heterogeneous condition caused by various underlying disorders and comorbidities. A cluster analysis is a statistical technique that attempts to group populations by shared traits. Applied to AF, it could be useful in classifying the variables and complex presentations of AF into phenotypes of coherent, more tractable subpopulations. Objectives This study aimed to characterize the clinical phenotypes of AF using a national AF patient registry using a cluster analysis. Methods We used data of an observational cohort that included 7406 patients with non-valvular AF enrolled from 158 sites participating in a nationwide AF registry (J-RHYTHM). The endpoints analyzed were all-cause mortality, thromboembolisms, and major bleeding. Results The optimal number of clusters was found to be 4 based on 40 characteristics. They were those with (1) a younger age and low rate of comorbidities (n = 1876), (2) a high rate of hypertension (n = 4579), (3) high bleeding risk (n = 302), and (4) prior coronary artery disease and other atherosclerotic comorbidities (n = 649). The patients in the younger/low comorbidity cluster demonstrated the lowest risk for all 3 endpoints. The atherosclerotic comorbidity cluster had significantly higher adjusted risks of total mortality (odds ratio [OR], 3.70; 95% confidence interval [CI], 2.37–5.80) and major bleeding (OR, 5.19; 95% CI, 2.58–10.9) than the younger/low comorbidity cluster. Conclusions A cluster analysis identified 4 distinct groups of non-valvular AF patients with different clinical characteristics and outcomes. Awareness of these groupings may lead to a differentiated patient management for AF.

It is very desirable to develop advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications. Herein, biomass‐derived multilayer‐structured absorbable microparticles (MQxTy) composed of starches and plant polyphenols are readily constructed for the safe and effective treatment of bone defects with intractable bleeding by coating multiple layers of quaternized starch (Q+) and tannic acid onto microporous starch microparticles via facile layer‐by‐layer assembly. MQxTy microparticles exhibit efficient degradability, low cytotoxicity, and good blood compatibility. Among various MQxTy microparticles with distinct Q+/T− double layers, MQ2T2 with outmost polyphenol layer possess the unique properties of platelet adhesion/activation and red blood cell aggregation, resulting in the best hemostatic performance. In a mouse cancellous‐bone‐defect model, MQ2T2 exhibits the favorable hemostatic effect, low inflammation/immune responses, high biodegradability, and promoted bone repair. A proof‐of‐concept study of beagles further confirms the good performance of MQ2T2 in controlling intractable bleeding of bone defects. The present work demonstrates that such biomass‐based multilayer‐structured microparticles are very promising biomedical materials for clinical use., Biomass‐derived multilayer‐structured hemostatic microparticles (MQ2T2) composed of starches and plant polyphenols are constructed to integrate the advantages of cationized amylopectin (with high viscosity), polyphenol (with unique properties in accelerating hemostasis), and multilayer structures (with favorable biodegradability), which can achieve effective (accelerated hemostasis and promoted bone repair) treatments of bone defects with intractable bleeding in mouse and beagle models.

Background Accurate detection of bleeding events from electronic health records (EHRs) is crucial for identifying and characterizing different common and serious medical problems. To extract such information from EHRs, it is essential to identify the relations between bleeding events and related clinical entities (eg, bleeding anatomic sites and lab tests). With the advent of natural language processing (NLP) and deep learning (DL)-based techniques, many studies have focused on their applicability for various clinical applications. However, no prior work has utilized DL to extract relations between bleeding events and relevant entities. Objective In this study, we aimed to evaluate multiple DL systems on a novel EHR data set for bleeding event–related relation classification. Methods We first expert annotated a new data set of 1046 deidentified EHR notes for bleeding events and their attributes. On this data set, we evaluated three state-of-the-art DL architectures for the bleeding event relation classification task, namely, convolutional neural network (CNN), attention-guided graph convolutional network (AGGCN), and Bidirectional Encoder Representations from Transformers (BERT). We used three BERT-based models, namely, BERT pretrained on biomedical data (BioBERT), BioBERT pretrained on clinical text (Bio+Clinical BERT), and BioBERT pretrained on EHR notes (EhrBERT). Results Our experiments showed that the BERT-based models significantly outperformed the CNN and AGGCN models. Specifically, BioBERT achieved a macro F1 score of 0.842, outperforming both the AGGCN (macro F1 score, 0.828) and CNN models (macro F1 score, 0.763) by 1.4% (P Conclusions In this comprehensive study, we explored and compared different DL systems to classify relations between bleeding events and other medical concepts. On our corpus, BERT-based models outperformed other DL models for identifying the relations of bleeding-related entities. In addition to pretrained contextualized word representation, BERT-based models benefited from the use of target entity representation over traditional sequence representation

Aim Cardiac arrest is the most serious complication in acute coronary syndromes. Glycoprotein IIb/IIIa inhibitors (GPI) are used in selected acute coronary syndrome patients. If the use of GPI leads to an increase in bleeding events and influences survival in patients after cardiac arrest is unknown. Methods We report retrospective data of a single center registry of patients after successful intra- and out-of-hospital cardiac arrest between 2002 and 2013. Inclusion criteria were survival for at least 6 h and successful percutaneous coronary intervention (PCI) within the first 24 h. Patients treated with other fibrinolytic agents or being supported by an extracorporeal life support system were excluded from the analysis. Results 310 patients were included in our study. 204 received GPI (GPI+), 106 did not (GPI−). Patients in the GPI+ group were significantly younger (62.8 vs. 68.0 years, p

Background: Since warfarin is primarily bound to serum albumin, hypoalbuminemia is likely to increase the free fraction of warfarin and to increase the risk of bleeding. We prospectively evaluated the impact of serum albumin levels (ALB) on international normalized ratio of prothrombin time (PT-INR) control and hemorrhagic events in atrial fibrillation (AF) patients treated with warfarin. Methods: Seven hundred fifty-five non-valvular AF patients on warfarin were enrolled. PT-INR control and major bleeding events (MB, International Society on Thrombosis and Haemostasis) were prospectively followed and were related to ALB at enrollment. Results: Twenty-seven patients developed MB during 1-year follow-up. In univariate/multivariate analyses, ALB (OR = 0.49, 95% CI 0.26–0.99, p = 0.04) and hemoglobin levels (OR = 0.78, 95% CI 0.65–0.92, p = 3.0 (ρ = −0.15, p

Graphical abstract, Background In the potent new antiplatelet era, it is important issue how to balance the ischemic risk and the bleeding risk. However, previous risk models have been developed separately for in-hospital mortality and major bleeding risk. Therefore, we aimed to develop and validate a novel combined model to predict the combined risk of in-hospital mortality and major bleeding at the same time for initial decision making in patients with acute myocardial infarction (AMI). Methods Variables from the Korean Acute Myocardial Infarction Registry (KAMIR) – National Institute of Health (NIH) database were used to derive (n = 8955) and validate (n = 3838) a multivariate logistic regression model. Major adverse cardiovascular events (MACEs) were defined as in-hospital death and major bleeding. Results Seven factors were associated with MACE in the model: age, Killip class, systolic blood pressure, heart rate, serum glucose, glomerular filtration rate, and initial diagnosis. The risk model discriminated well in the derivation (c-static = 0.80) and validation (c-static = 0.80) cohorts. The KAMIR-NIH risk score was developed from the model and corresponded well with observed MACEs: very low risk (0.9%), low risk (1.7%), moderate risk (4.2%), high risk (8.6%), and very high risk (23.3%). In patients with MACEs, a KAMIR-NIH risk score ≤ 10 was associated with high bleeding risk, whereas a KAMIR-NIH risk score > 10 was associated with high in-hospital mortality. Conclusion The KAMIR-NIH in-hospital MACEs model using baseline variables stratifies comprehensive risk for in-hospital mortality and major bleeding, and is useful for guiding initial decision making.

Background Geriatric conditions, such as frailty and cognitive impairment, are prevalent in older patients with atrial fibrillation (AF). We examined the prognostic value of geriatric conditions for predicting 1-year mortality and bleeding events in these patients. Methods SAGE (Systematic Assessment of Geriatric Elements)-AF study is a multicenter cohort study which enrolled individuals (mean age 75 years, 48% women, 86% taking oral anticoagulation) 65 years and older with AF and CHA2DS2 -VASc score of 2 or higher from clinics in Massachusetts and Georgia, USA between 2016 and 2018. A six-component geriatric assessment included validated measures of frailty, cognitive function, social support, depressive symptoms, vision, and hearing was performed at baseline. Study endpoints included all-cause mortality and clinically relevant bleeding. Results At 1 year, 1,097 (96.5%) individuals attended the follow up visit, 44 (3.9%) had died, and 56 (5.1%) had clinically relevant bleeding. After adjustment for demographic and clinical factors, social isolation (odds ratio [OR] 1.69, 95% confidence interval [CI]: 1.01–2.84), depression (OR 1.94, 95% CI: 1.28–2.95) and frailty (OR 2.55, 95% CI: 1.55–4.19) were significantly associated with the composite endpoint of death or clinically relevant bleeding. After multivariable adjustment, depression (OR 1.79, 95% CI 1.09–2.93) and frailty (OR 2.83, 95% CI 1.55–5.17) were significantly associated with clinically relevant bleeding. Conclusions Social isolation, depression, and frailty were prognostic of dying or experiencing clinically relevant bleeding during the coming year in older men and women with AF. Assessing geriatric impairments merits consideration in the care of these patients.

Background Over the years, the internet has enabled considerable progress in the management of chronic diseases, especially hypertension and diabetes. It also provides novel opportunities in online anticoagulation management. Nevertheless, there is insufficient evidence regarding the effectiveness of online anticoagulation management. Objective This study explored the effectiveness and safety of warfarin management via the Alfalfa app, so as to provide evidence in support of anticoagulant management through online services. Methods In this retrospective, observational cohort study, 824 patients were included. In the offline group, patients went to the hospital clinic for warfarin management. In the Alfalfa app group, patients reported the dose of warfarin, current international normalized ratio (INR) value, and other related information through the Alfalfa app. Physicians or pharmacists used the app to adjust the dose of warfarin and determined the time for the next blood INR testing. Patients completed INR testing by point-of-care at home or hospital. The primary outcome of the study was the percentage of time in therapeutic range (TTR). Secondary outcomes included minor and major bleeding events, thrombotic events, warfarin-related emergency department visits, hospital admissions, and high INR values. Results The TTR and percentage of INR values in the range were significantly higher in the Alfalfa app group than in the offline group (79.35% vs 52.38%, P Conclusions Warfarin management is superior via the Alfalfa app than via offline services in terms of major bleeding events, warfarin-related emergency department visits, and hospital admissions.

The risk and timing of bleeding events following ultrasound-guided percutaneous renal biopsy are not clearly defined.We performed a retrospective study of 617 consecutive adult patients who underwent kidney biopsy between 2012 and 2017 at a tertiary academic hospital in London, Canada. We assessed frequency and timing of minor (not requiring intervention) and major (requiring blood transfusion, surgery, or embolization) bleeds and developed a personalized risk calculator for these.Bleeding occurred in 79 patients (12.8%; 95% confidence interval [CI]: 10.4%-15.7%). Minor bleeding occurred in 67 patients (10.9%; 95% CI: 8.6%-13.6%). Major bleeding occurred in 12 patients (1.9%; 95% CI: 1.1%-3.4%); 2 required embolization or surgery (0.3%; 95% CI: 0.09%-1.2%) and 10 required blood transfusion (1.6%; 95% CI: 0.9%-3.0%). Seventy-three of 79 events were identified immediately on post-procedure ultrasound (92.4% of cases; 95% CI: 84.4%-96.5%). Four of 617 patients experienced a minor event not detected immediately (0.6%; 95% CI: 0.3%-1.7%). Two patients (0.3%; 95% CI: 0.09%-1.2%) suffered a major complication that was not recognized immediately; both required blood transfusions only. There were no deaths or nephrectomies. A risk calculator using age, body mass index, platelet count, hemoglobin concentration, size of the target kidney, and whether the kidney is native, or an allograft predicted minor (C-statistic, 0.70) and major bleeding (C-statistic, 0.83).This retrospective study of 617 patients who had percutaneous ultrasound-guided renal biopsies supports the safety of short post-biopsy monitoring for most patients. A risk calculator can further personalize estimates of complication risk (http://perioperativerisk.com/kbrc).Les risques d’hémorragie et le moment où surviennent ces événements après une biopsie rénale percutanée échoguidée ne sont pas clairement définis.Nous avons procédé à une étude rétrospective sur 617 patients adultes consécutifs ayant subi une biopsie rénale entre 2012 et 2017 dans un center hospitalier universitaire de soins tertiaires de London, au Canada. Nous avons analysé la fréquence des saignements et le moment où est survenue une hémorragie mineure (ne nécessitant aucune intervention) ou majeure (nécessitant une transfusion sanguine, une chirurgie ou une embolisation). Un calculateur de risque a ultérieurement été développé pour chacun.Des 617 patients étudiés, 79 (12,8 %; IC 95 % : 10,4 %-15,7 %) ont vécu un événement hémorragique mineur (n=67 [10,9 %]; IC 95 % : 8,6 %-13,6 %) ou majeur (n=12 [1,9 %]; IC 95 % : 1,1 %-3,4 %). Deux hémorragies majeures ont nécessité une embolisation ou une chirurgie (0,3 %; IC 95 % : 0,09 %-1,2 %), les dix autres ayant été traitées par transfusion sanguine (1,6 %; IC 95 % : 0,9 %-3,0 %). Des 79 événements rapportés, 73 ont été détectés à l’échographie immédiatement après l’intervention (92,4 % des cas; IC 95 % : 84,4 %-96,5 %). Quatre patients (0,6 %; IC 95 % : 0,3 %-1,7 %) ont subi une complication mineure n’ayant pas été détectée immédiatement après la biopsie. Deux patients (0,3 %; IC 95 % : 0,09 %-1,2 %) ont souffert d’une complication majeure n’ayant pas été reconnue immédiatement, mais qui n’a nécessité que des transfusions sanguines. Aucun décès ou néphrectomie n’a été rapporté. Un calculateur du risque d’hémorragie utilisant l’âge, l’indice de masse corporelle, la numération plaquettaire, le taux d’hémoglobine, la taille du rein biopsié, et tenant compte du fait que le rein est natif ou une allogreffe, a pu prédire un événement mineur (statistique C = 0,70) ou majeur (statistique C = 0,83).Cette étude rétrospective sur 617 patients confirme qu’il serait prudent d’assurer une surveillance de courte durée pour la plupart des patients qui subissent une biopsie percutanée échoguidée. L’emploi d’un calculateur du risque d’hémorragie précise davantage le risque de complications estimé (http://perioperativerisk.com/kbrc).

Introduction At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings. Materials and methods In vitro, the influence of sunitinib, sorafenib, and bevacizumab on platelet aggregation, P-selectin expression and fibrinogen binding, platelet–EC interaction, and tyrosine phosphorylation of c-Src was studied by optical aggregation, flow cytometry, real-time perfusion, and western blotting. Ex vivo, platelet aggregation was analyzed in 25 patients upon sunitinib or bevacizumab treatment. Concentrations of sunitinib, VEGF, and platelet and EC activation markers were measured by LC–MS/MS and ELISA. Results In vitro, sunitinib and sorafenib significantly inhibited platelet aggregation (20 μM sunitinib: 71.3%, p

Hypothetically, diminished platelet reactivity (PR) during dual antiplatelet therapy (DAPT) should cause extra major bleeding events (MBE), although definite evidence is lacking. Multiple scores have been proposed to stratify bleeding risk, but their predictive value during DAPT is unclear. We compared the performance of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) with PR testing to predict MBE in Korean patients with acute coronary syndrome. We screened 1105, and included 903 consecutive patients who underwent coronary interventions. All patients received DAPT, while MBE were assessed by BARC scale. Admission platelet reactivity was assessed with VerifyNow Analyzer simultaneously with CRUSADE score, and MBE were collected at 1 month and at 1 year post stenting. There were a total of 113 (11%) MBE at 1 month, and extra 41(5%) MBE at 1 year. At 1 month MBE prediction was superior by CRUSADE score (AUC: 0.816, 95% CI: 0.79 0.84, p, Highlights • Dual antiplatelet therapy for 1 year is a golden standard following coronary stenting in patients with acute coronary syndromes. • Bleeding is a life-threatening major complication associated with chronic aggressive antiplatelet strategies. • Predicting bleeding based on clinical features or established biomarkers is upmost yet unsolved mystery affecting clinical outcomes in such high-risk patients • The CRUSADE clinical score predicts bleeding better than platelet reactivity indices • Short-term bleedings at 30 days, but not delayed 1-yearly hemorrhages were better predicted by CRUSAIDE in East Asians. Dual antiplatelet therapy for 1 year is common following coronary stenting in patients with acute coronary syndromes. However, bleeding is a life-threatening major complication and shortcoming associated with chronic aggressive antiplatelet strategies. CRUSADE score was introduced for better prediction of in-hospital bleeding, while delayed bleeding risks remained unclear. Usually bleeding risk is assessed based on clinical features or by established biomarkers We tested the hypothesis on the superiority of CRUSADE score versus conventional platelet reactivity in a large Korean registry, and revealed the following: major bleeding events in real life are more frequent, and are heavily unreported in clinical trials; the CRUSADE clinical score predicts bleeding better than platelet reactivity indices. Unfortunately, short-term bleedings at 30 days, but not delayed 1-yearly hemorrhages were better predicted by CRUSADE in East Asians.

INTRODUCTION Laparoscopic myomectomy (LM) can be associated with significant bleeding. AIM To identify factors influencing the postoperative hemoglobin (Hb) drop after LM. MATERIAL AND METHODS This is a retrospective, single-center study. We evaluated data of 150 consecutive patients undergoing LM due to intramural myomas between 2010 and 2015. RESULTS The median age of the patients was 37 (23-53) years. The mean diameter of the largest myoma was 5.7 ±2.3 (1.5-12) cm. The mean surgical time was 83 ±38 (35-299) min. The median number of sutures was 3 (1-11). The mean postoperative Hb drop was 1.6 ±1.2 (0-6) g/dl, and the mean estimated blood loss was 261 ±159 (50-1700) ml. In the univariate analysis, the postoperative Hb drop correlated with the duration of surgery (p < 0.001), diameter of the largest myoma (p < 0.001), cumulative myoma weight (p < 0.001), and number of sutures (p < 0.001), but not with patients' age or number of intramural myomas. In the multivariable analysis, the surgical time (β = 0.395, p < 0.001), diameter of the largest myoma (β = 0.292, p = 0.03) and preoperative Hb concentration (β = 0.299, p < 0.001) predicted the postoperative Hb change. CONCLUSIONS Surgical time and dominant myoma diameter are independent predictors of the postoperative Hb drop after LM.

Introduction: Humeral shaft fractures are quite common in orthopedics and represent 1-3% of adult fractures. The surgical treatment is the a better choice in order to obtain a reduction and stable alignment and to prevent the complications. The goal of this study was to compare the three techniques (IMN, LCP and EF) in the treatment of diaphyseal fractures of the humerus in the adult patient. Materials and Methods: We examined 79 patients with diaphyseal fractures of the humerus. 32 were treated with plaque (LCP), 26 with intramedullary nail (IMN) and 21 with eternal fixer (FE) The clinical and radiographic follow-up was done at 1.3, 6 and 12 months. As rating scales we used the ASES and SF-36. We recorded all the complications. Results: The median follow-up was 11.5 months (9-16). The operative time was significantly smaller in the case of FE (47 ‘) with a statistically significant difference compared with other techniques. Even the blood loss was lower in the case of FE (60ml), compared to nails (160ml) and LCP (330ml) p

In 2014, a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary or valve interventions was published, which represented an effort of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Since publication of this document, additional data from observational cohorts, randomized controlled trials, and percutaneous interventions as well as new guidelines have been published. Moreover, new drugs and devices/interventions are also available, with an increasing evidence base. The approach to managing AF has also evolved towards a more integrated or holistic approach. In recognizing these advances since the last consensus document, EHRA, WG Thrombosis, EAPCI, and ACCA, with additional contributions from HRS, APHRS, Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), proposed a focused update, to include the new data, with the remit of comprehensively reviewing the available evidence and publishing a focused update consensus document on the management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing percutaneous coronary or valve interventions, and providing up-to-date consensus recommendations for use in clinical practice.

Summary Venous thromboembolism (VTE)‐BLEED, a decision tool for predicting major bleeding during chronic anticoagulation for VTE has not yet been validated in practice‐based conditions. We calculated the prognostic indices of VTE‐BLEED for major bleeding after day 30 and day 90, as well as for recurrent VTE and all‐cause mortality, in 4457 patients enrolled in the international, prospective XALIA study. The median at‐risk time was 190 days (interquartile range 106–360). The crude hazard ratio (HR) for major bleeding after day 30 was 2·6 [95% confidence interval (CI) 1·3–5·2] and the treatment‐adjusted HR was 2·3 (95% CI 1·1–4·5) for VTE‐BLEED high (versus low) risk patients: the corresponding values for major bleeding after day 90 were 3·8 (95% CI 1·6–9·3) and 3·2 (95% CI 1·3–7·7), respectively. The predictive value of VTE‐BLEED was similar in selected patients with unprovoked VTE or those treated with rivaroxaban. High VTE‐BLEED score was associated with higher incidence of all‐cause mortality (treatment‐adjusted HR 11, 95% CI 4·8–23), but not evidently with recurrent VTE (treatment‐adjusted HR 1·5; 95% CI 0·85–2·7). These results confirm the predictive value of VTE‐BLEED in practice‐based data in patients treated with rivaroxaban or conventional anticoagulation, supporting the hypothesis that VTE‐BLEED may be useful for making management decisions on the duration of anticoagulant therapy.

The purpose of this study was to investigate the overall incidence and relative risk (RR) of hemorrhagic events in cancer patients treated with ramucirumab. 298 potentially relevant citations on ramucirumab from Pubmed, Web of Science and the Cochrane Database, as well as abstracts presented at conferences (all up to March 2016) were identified through our initial search. Only phase II and III prospective clinical trials of ramucirumab among cancer patients with toxicity records on hemorrhagic events were selected for final analysis. Data was extracted from the original studies by two independent reviewers. The overall incidence, RR, and 95% confidence intervals (CI) were calculated using fixed or random effects models according to the heterogeneity of the enrolled studies. The statistical analysis was performed by STATA version 11.0 (Stata Corporation, College Station, TX). 4963 patients with a variety of solid tumors from eleven eligible studies were selected into our analysis. The results demonstrated that the overall incidences of all-grade and high-grade hemorrhagic events in cancer patients were 27.6% (95% CI, 18.7-36.5%) and 2.3% (95% CI, 1.3-3.2%), respectively. The RR of hemorrhagic events of ramucirumab compared to control was significantly increased for low-grade (RR, 2.06; 95% CI, 1.85-2.29, p < 0.001), but not for high-grade (RR, 1.19, 95% CI, 0.80-1.76, p=0.39) hemorrhagic events. Hemorrhagic events associated with ramucirumab are modest and manageable while patients could continue to receive ramucizumab treatment to achieve their maximum clinical benefits.