Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.     

ITP患者血小板活化依赖性自身抗原的研究

本文采用改良单克隆抗体特异性抗原捕获酶免疫法(MACE)使用5种抗原血小板单克隆抗体对59例ITP患者进行了相关自身抗原研究,结果28例ITP患者血浆呈现抗血小板自身抗体阳性(47.46％),其中单独抗GPI_b/2例、抗GPⅡ_b/Ⅲ_α5例、抗α颗粒膜蛋白-1401例,抗凝血酶敏感蛋白6例,另14例出现2种以上自身抗体,以抗GPⅡ_b/Ⅲ_α为多见。找们建议将以上抗体针对的抗原称为血小板活化依赖性自身抗体。虽然我们未发现这类自身抗原与其它类型自身抗原间的临床表现及治疗结果存在明显差异,但这类自身抗原应引起重视,有必要对此作进一步观察和深入研究。     

Managing abnormal blood lipids: a collaborative approach

Current data and guidelines recommend treating abnormal blood lipids (ABL) to goal. This is a complex process and requires involvement from various healthcare professionals with a wide range of expertise. The model of a multidisciplinary case management approach for patients with ABL is well documented and described. This collaborative approach encompasses primary and secondary prevention across the lifespan, incorporates nutritional and exercise management as a significant component, defines the importance and indications for pharmacological therapy, and emphasizes the importance of adherence. Use of this collaborative approach for the treatment of ABL ultimately will improve cardiovascular and cerebrovascular morbidity and mortality.     

Recommendations for the management of prosthetic valve thrombosis

Prosthetic valve thrombosis (PVT) is a life-threatening disease, for which treatment strategies have been controversial. Herein, existing data on management options are reviewed, and conclusions drawn as to the choice and use of treatment strategies for PVT. The use of transesophageal echocardiography (TEE) allows distinction to be made between obstructive and non-obstructive PVT by the presence or absence of occluder motion limitation. The differentiation of PVT from pannus and vegetation is, however, still limited by TEE. The incidence of PVT has been underestimated by not taking into account a large percentage of non-obstructive PVT. Although the standard treatment for PVT has been surgery, thrombolysis has lower mortality rates, particularly in patients in NYHA functional classes III-IV. The lowest complication rates with thrombolysis have been achieved in patients with non-obstructive PVT. Pregnancy, left atrial appendage thrombi and large PVT are not contraindications to thrombolysis. The third therapeutic option is anticoagulant therapy. The detrimental effect of anticoagulant treatment in obstructive PVT was shown in a prospective study. Non-obstructive thrombi of > 5 mm length have been treated with higher success rates and lower complication rates by thrombolysis than by anticoagulant treatment. In conclusion, all patients with suspected PVT should undergo multiplane TEE. Thrombolysis is the first-line treatment for obstructive PVT, independent of NYHA class and thrombus size if there are no contraindications. Serial TEE studies must be conducted during thrombolysis. Surgery should be reserved for those patients in whom thrombolysis is contraindicated, or has failed. Initial anticoagulant therapy is recommended only for small, non-obstructive PVT if anticoagulation had been subtherapeutic; otherwise, thrombolysis is the treatment of choice if there are no contraindications.     

Recommendations for reporting morbid events after heart valve surgery

Major reasons for the considerable heterogeneity among published results of heart valve surgery are inconsistency in follow up techniques, reporting systems and classification of adverse events. The present recommendations are intended to harmonize the presentation of clinical material in order to improve comparison of data from different sources for the analysis of pooled data. The quality of an observational study is largely, if not entirely, due to the follow up technique, which may be graded according to six categories: Self-reporting of adverse events/well-being by the patients may be classified 'excellent'; if the information is gathered and re-checked at short-term intervals. Data obtained from in-hospital or outpatient examinations by qualified examiners at least twice a year or other personal contact through qualified examiners may be regarded as 'sufficient', if the results are re-checked by contacting the treating home physician. All other follow up techniques may be regarded as inappropriate. Consequences of complications are entirely dependent on severity and possible sequelae. It is therefore recommended to grade any reported complication according to its severity by utilizing a score system. Embolisms are best categorized by utilizing the performance status scale. Bleeding events may be categorized according to severity as fatal, major (requiring hospital transmission with transfusion, surgery or with permanently increased disability) or minor (not requiring hospital admission, surgery or transfusion). In some cases it will remain unclear whether an event was primarily embolic or hemorrhagic. These complications should be summarized as 'not categorized'. The reporting of morbid events due to thrombosis, embolism and bleeding should go along with information regarding the quality of antithrombotic management.     

Clinical significance of a single measurement of troponin-I and C-reactive protein at admission in 1773 consecutive patients with acute coronary syndromes

Background

The clinical significance of biochemical markers of myocardial damage or inflammation has not been prospectively established in populations representing the whole spectrum of acute coronary syndromes. We investigated whether the elevation of these biomarkers at admission has a prognostic value that is independent and incremental to baseline clinical variables and quantitative electrocardiographic ischemia.

Methods

We measured blood levels of cardiac troponin I (cTnI) and C-reactive protein (CRP) in 1773 consecutive patients admitted to 31 Italian coronary care units within 12 hours from an episode of acute coronary syndrome. Primary and secondary outcomes were (1) 30-day incidence of death or nonfatal (re)infarction and (2) death alone.

Results

In a multivariate model, cTnI was independently associated with the risk of death or (re)infarction (OR, 1.8; 95% CI, 1.2 to 2.6; P = .002) and death (OR, 2.2; 95% CI, 1.4 to 3.4; P < .001), whereas CRP was of borderline significance for the primary outcome but was associated with death (OR, 1.4; 95% CI, 1.0 to 2.1; P = .06, and OR, 1.7; 95% CI, 1.1 to 2.6; P = .01, respectively). However, the inclusion of the biomarkers did not increase the prognostic capacity of the clinical risk model (C-index of both models with and without biomarkers was 0.73 for the primary outcome measures and 0.80 for the secondary outcome measures). CRP further stratified cTnI-negative patients. The prognostic significance of the biomarkers was similar in patients with and in those without persistent ST-segment elevation.

Conclusions

In acute coronary syndromes, the elevation of cTnI and CRP at admission has an independent prognostic value that is not incremental to baseline clinical variables and quantitative electrocardiographic ischemia.     

Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47–58): use of direct acting oral anticoagulants

We studied the efficacy and safety of humanized CAR-T therapy following intensive chemotherapy for refractory/relapsed (R/R) acute lymphoblastic leukaemia (B-ALL). Twenty-three patients with R/R B-ALL were pretreated with intensive chemotherapy (fludarabine combined with medium-dose cytarabine) 12 days before CAR-T therapy. Adverse events (AEs), curative effects, infection indicators and cytokine release syndrome (CRS) were monitored. Each of the 23 patients received a dose of 1·0 × 10⁶ cells/kg CAR-T cell infusion on day 0. After 14 days, 19 patients (82·61%) achieved complete response (CR) or CR with incomplete count recovery. No survival benefit was achieved with consolidative haematopoietic stem-cell transplantation (HSCT), with a median follow-up of 14·0 months (range, 1·5–21·0 months). The notable AEs were grade 1–2 CRS in 18 patients, while the other five patients were grade 3 CRS. No patients died of CRS. Only one patient died of respiratory failure due to cytomegalovirus infection 24 days after infusion. The proportion of leukaemic cells in bone marrow on infusion day and the peaks of IL-6, TNF-α and IL-8 levels were correlated with CRS levels. A lower disease burden was achieved by intensive lymphodepleting chemotherapy, and the subsequent CAR-T therapy had a high response and manageable toxicity. Trial registration: The patients were enrolled in a clinical trial of ChiCTR-ONN-16009862, and ChiCTR1800019622.     

罕见遗传性出血性疾病诊断与治疗中国专家共识(2021年版)

一、概述在遗传性凝血因子缺乏症中,缺乏凝血因子Ⅷ、Ⅸ的血友病A及血友病B相对常见,与血管性血友病(VWD)构成了95%~97%的遗传性出血性疾病,目前已有独立的血友病及VWD相关中国专家共识/指南[1-2]。本共识所指的罕见遗传性出血性疾病(Rare inherited bleeding disorders,RBD)包括遗传性纤维蛋白原缺乏症(FⅠD)、凝血酶原缺乏症(FⅡD)、凝血因子Ⅴ缺乏症(FⅤD)、凝血因子Ⅴ和Ⅷ联合缺乏症(FⅤ+ⅧD)、凝血因子Ⅶ缺乏症(FⅦD)、凝血因子Ⅹ缺乏症(FⅩD)、凝血因子Ⅺ缺乏症(FⅪD)、凝血因子??缺乏症(F??D)及维生素K依赖性凝血因子缺乏症(VKDFD)。