Measurement of thrombin generation intra-operatively and its association with bleeding tendency after cardiac surgery

Introduction

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.

Materials and Methods

Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.

Results

TG diminished significantly (p < 0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p < 0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p < 0.05) with postoperative blood loss.

Conclusions

TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively.     

Editor's choice: A phase II,multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study

Background

The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin. In previous phase II trials (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival. This multicenter, single-arm phase II clinical trial (ACT III) was performed to confirm these results.

Methods

Rindopepimut and standard adjuvant temozolomide chemotherapy were administered to 65 patients with newly diagnosed EGFRvIII-expressing (EGFRvIII+) glioblastoma after gross total resection and chemoradiation.

Results

Progression-free survival at 5.5 months (∼8.5 mo from diagnosis) was 66%. Relative to study entry, median overall survival was 21.8 months, and 36-month overall survival was 26%. Extended rindopepimut vaccination (up to 3.5+ years) was well tolerated. Grades 1–2 injection site reactions were frequent. Anti-EGFRvIII antibody titers increased ≥4-fold in 85% of patients, and increased with duration of treatment. EGFRvIII was eliminated in 4/6 (67%) tumor samples obtained after >3 months of therapy.

Conclusions

This study confirms, in a multicenter setting, the preliminary results seen in previous phase II trials of rindopepimut. A pivotal, double-blind, randomized, phase III trial (“ACT IV”) is under way.     

Ma vérité, leurs vérités. Réflexions sur l’influence du contexte sur un fait judiciaire

The context has an important role on the behaviors and meanings that even some aspects of it are distorted, amplified or manipulated by the media. These contexts are increasingly difficult to understand because of the theatricality of our society. Sometimes it promotes certain abuses, creates guilt and gives a biased reading of events before any judgment source of morbid rationalism. Orchestrate by the media world located more in a temporality of the moment without feedback, it is increasingly virtual. The reality that builds on the previously constructed chimera is life in a time of increasingly shifted with the judicial time left to graze the absurd. In addition, the context is difficult to grasp by the judges. Indeed, in many judgments, including cases with families of judges, only lawyers have the right to speak and the volume of work has little time to understand it. The matrix model ACT is a tool that can illuminate our understanding of certain actions that give them different meanings depending on the individual in relation to what is important to them and their needs. A study of the context seems crucial in understanding a judicial fact and to understand its reality. In addition, in many complaints daily time listening and mediation avoid judgments which complicates it. In addition, if the context cannot be at the helm, it is interesting to look at the responsibility of the media in the staging environment to build a useful context to the show.     

Successful treatment of eosinophilic otitis media associated with severe bronchial asthma with an anti-IL-5 monoclonal antibody,mepolizumab

Eosinophilic otitis media (EOM), which is characterized by the accumulation of eosinophils in middle ear effusion and the middle ear mucosa, is a refractory type of otitis media that is often associated with asthma. Although an early diagnosis and appropriate treatment are necessary to prevent the progression of hearing loss in patients with EOM, there are currently no well-established treatments for this condition. We treated a 60-year-old male patient with asthma and EOM. The patient’s asthma was poorly controlled, despite the use of high-dose inhaled corticosteroids, long-acting beta-agonist treatment, and the regular use of systemic corticosteroids. Mepolizumab, an anti-IL-5 monoclonal antibody, was started to treat the patient’s refractory asthma. At 4 months after the initiation of mepolizumab treatment, the patient’s asthma, hearing, and middle ear effusion improved. The present case suggests that mepolizumab therapy can control EOM and asthma.     

The changing face of central chondrosarcoma of bone. One UK-based orthopaedic oncology unit’s experience of 33 years referrals

AimTo ascertain the changing incidence over time of the three commonest primary sarcomas of bone. Data obtained with particular reference to central chondrosarcoma from the annual referral rate to a large UK-based specialist orthopaedic oncology unit. To discuss how the “barnyard pen” analogy of cancers previously applied to certain commoner cancers can also be applicable to central chondrosarcoma (CS) of bone.Materials and methodsA retrospective review was conducted of a computerised database identifying all central cartilage tumours (CCT) of bone, including enchondroma and CS subtypes, between 1985 and 2018. These were compared with the referrals of the other two commonest primary sarcomas of bone, osteosarcoma and Ewing sarcoma.ResultsThere was a total of 1507 CS showing a 68% overall increase in annual referral rate/incidence over the study period. 68% cases were the borderline malignant lesions now known as atypical cartilaginous tumour (ACT). The annual referral rate/incidence of this entity increased by 194% over the 30 years. Whereas, the annual referral rate/incidence for osteosarcoma and Ewing sarcoma was static for the past 20 years.ConclusionThe annual incidence of central CS of bone showed a marked increase over the 33-year period as compared with both osteosarcoma and Ewing sarcoma. This is especially in the ACT category and is thought to be due to the increased provision of MRI scanning flagging up a rise in incidental findings. The spectrum of CCTs from benign to highly malignant elegantly fits the “barn yard” pen analogy and could prove useful as an explanatory tool for patients and clinicians unfamiliar with these diseases.