Current anticoagulant safety

INTRODUCTION: Currently used anticoagulants such as unfractionated heparin, low-molecular-weight heparin and vitamin K antagonists, have several drawbacks, mostly related to safety. In this review, we will briefly discuss and compare the safety of anticoagulation therapy with 'old' and new agents. AREAS COVERED: Safety issues with anticoagulation therapy are mostly related to bleeding. The intensity of anticoagulation is related to the risk of bleeding and thus, for the efficacy not to be affected, must be maintained at the lower effective intensity. Several improvements have been made in the management of anticoagulation therapy; these include monitoring, pathology-based treatment schemes taking into account patient characteristics, patient education and the introduction of anticoagulation centers. Safety of novel anticoagulants is encouraging. EXPERT OPINION: Novel agents have the potential to compete with existing therapy for thromboprophylaxis, treatment and stroke prevention in atrial fibrillation. Promising results have emerged from trials comparing them with existing treatment. Not long from now we will see these new agents in the armamentarium of antithrombotic drugs.     

Chromosome 9p and 10q losses predict unfavorable outcome in low-grade gliomas

The loss of chromosomes 1p–19q is the only prognostic molecular alteration identified in low-grade gliomas (LGGs) to date. Search for loss of heterozygosity (LOH) on chromosomes 1p, 9p, 10q, and 19q was performed in a series of 231 LGGs. Loss of chromosomes 1p–19q was strongly correlated with prolonged progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analyses. LOH on 9p and 10q were associated with shortened PFS (P = .01 and .03, respectively) on univariate analysis. On multivariate analysis, LOH on 9p remained significant for PFS (P = .05), whereas LOH on 10q had a significant effect on OS (P = .02). Search for LOH 9p and 10q appears to be a useful complement to analysis of chromosomes 1p–19q in LGGs.     

Midline carcinoma expressing NUT in malignant effusion cytology

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare and aggressive subset of poorly differentiated squamous cell carcinoma that is defined by t(15,19) and typically presents in the midline structures of the head, neck, and mediastinum. We report two cases of NMC that presented uniquely with malignant pleural and pericardial effusions including one with cardiac tamponade at presentation. The first case is of a 25‐year‐old male patient who presented with progressive dyspnea associated with palpitations and dizziness on standing, found to have large bilateral pleural effusions. The second case is of a previously healthy 29‐year‐old male patient who presented with progressive dyspnea, cough with expectoration, and a large right lower neck mass of 3 months onset, and a large left pleural effusion and left lung infiltrate on imaging studies. Both cases showed malignant cells on cytology suggestive of poorly differentiated carcinoma. Subsequent histopathological and immunochemistry studies were consistent with the diagnosis of NMC. Both patients had a rapid decline in status and suffered comorbidities secondary to their carcinoma, inevitably leading to their death. It is important to consider NUT midline carcinomas can present in a variety of clinical scenarios, and it is important to consider in the differential diagnoses when evaluating malignant effusion cytology. Utilization of ancillary testing with a broad immunostain profile including NUT studies, as well as fluorescent in‐situ hydridization (FISH) studies are helpful and necessary in making the appropriate diagnosis.     

Gated SPECT evaluation of outcome after abciximab-supported primary infarct artery stenting for acute myocardial infarction: the scintigraphic data of the abciximab and carbostent evaluation (ACE) randomized trial.

We used gated SPECT to evaluate the impact of abciximab on the efficacy of myocardial reperfusion in patients with acute myocardial infarction undergoing infarct-related artery stenting. METHODS: The Abciximab and Carbostent Evaluation (ACE) trial randomized 400 infarct patients to stenting alone or stenting plus abciximab. One-month (99m)Tc-sestamibi gated SPECT was planned in a subgroup of consecutive patients to evaluate infarct size, infarct severity, left ventricular volumes, and ejection fraction. RESULTS: The final study population included 182 patients (99 randomized to abciximab and 83 to stenting alone). Gated SPECT revealed smaller infarcts in the abciximab group than in the stenting-alone group (14.3% +/- 11.7% vs. 18.1% +/- 13%, P < 0.02), and lower infarct severity (minimum-to-maximum count ratio = 0.47 +/- 0.17 vs. 0.41 +/- 0.15, P < 0.02), resulting in a smaller left ventricular end-diastolic volume index (57.8 +/- 20.0 vs. 64.6 +/- 20.8 mL/m(2), P = 0.03) and left ventricular end-systolic volume index (31.7 +/- 17.4 vs. 37.5 +/- 18.6 mL/m(2), P = 0.05) in the abciximab group. One-month left ventricular ejection fraction was significantly higher in patients randomized to abciximab (47.4% +/- 11.3% vs. 43.9% +/- 11.7%, P = 0.05). CONCLUSION: The use of abciximab therapy as an adjunct to infarct-related artery stenting leads to a reduction in infarct size and severity, resulting in smaller 1-mo left ventricular volumes and better left ventricular function. Gated SPECT appears to be an ideal tool for outcome assessment in infarct patients undergoing different treatment strategies.     

MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities

MGMT promoter methylation, which has been correlated with the response to alkylating agents, was investigated in a retrospective series of 219 glioblastomas (GBMs) treated with various modalities. MGMT methylation had no impact on survival for the whole group, but showed a significant advantage (17.1 months vs. 13.1) for patients treated with RT+ adjuvant chemotherapy (relative risk of death (RR) = 0.53; P = 0.041), particularly when patients received CT during the course of RT (MS = 19.9 months vs. 12.5 months; RR = 0.227, P = 0.001). This suggests that the prognostic impact of MGMT methylation is dependent on therapeutic modalities and schedules. MGMT methylation was not correlated with the main molecular alterations, such as 10q loss and p53 expression.