抗TGF—β2抗体对青光眼术后滤过泡成纤维细胞凋亡的影响

目的观察抗转化生长因子-β2（Anti-Transforming Growth Factor-β2 Antibody，rhAnti-TGF—β2 mAb）抗体对体外培养的小梁切除术后失败滤过泡成纤维细胞凋亡及caspase-3的表达的影响。方法利用手术修复小梁切除术后失败的滤过泡时切除下来的瘢痕组织进行原代细胞培养，获得成纤维细胞（fibroblasts，FB）。将不同浓度的0、0．01、0．1、1μg/ml抗TGF-β2抗体作用于FB 24h以及用半数抑制浓度（IC50）0．14μg／ml作用0、24、48、72h，利用流式细胞仪、免疫组化法检测抗TGF—β2抗体诱导FB凋亡的情况及caspase-3的表达。结果在FB中加入不同浓度的抗体作用24h及IC50浓度处理FB0、24、48、72h，结果显示随着抗体浓度增大，作用时间延长，FB棕褐色的caspase-3强阳性表达增加，抗TGF-β2抗体高浓度组可见明显的亚二倍体凋亡峰，凋亡率为（9．8＋1．3）％。结论抗TGF-β2抗体能诱导FB凋亡，caspase-3参与了诱导的凋亡过程。     

Is the early cyclosporine A level predictive of the outcome of immunosuppressive therapy in severe aplastic anemia?

Immunosuppressive therapy (IST) has provided an alternative treatment option for cure of aplastic anemia patients who cannot receive bone marrow transplantation. Although there have been many recent studies on the efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there is no data on the correlation between the variability of CsA levels and the response to IST. Therefore, we retrospectively assessed the factors associated with IST efficacy in patients with acquired severe aplastic anemia (SAA). Sixty‐six patients were treated with ATG combined with CsA for 6 months. In the response group, the CsA levels were increased rapidly to more than 200 ng/mL within the first 2 wk after starting the IST. However, the non‐response group had a pattern of slower increase of the CsA levels. The CsA levels, during the first and second week of treatment with IST, were significantly different in the responders and non‐responders. The factors predictive of response to IST and survival were analyzed. The univariate analysis showed that a younger age at the initiation of IST, a high absolute neutrophil count prior to starting IST, a short interval between the diagnosis and initiation of IST, and high CsA levels during the first and second week of IST treatment were positively associated with the response rate and overall survival. The multivariate analysis showed that these four factors were independent factors associated with a longer patient survival. A high response rate was associated with a short interval between diagnosis and initiation of IST as well as high CsA levels during the first and second week of IST. Therefore, early intensification of CsA levels might improve patient outcome.     

Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena

Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disorder for which the best therapeutic option is not yet well established. Immune-related disorders are rare complications of MCD. We report on an MCD case in a 23-year-old patient with extensive abdominal involvement and associated immune hemolytic anemia and Raynaud phenomenon. He was negative for human immunodeficiency virus (HIV) and human herpesvirus-8 (HHV-8). After 8 courses of the anti-CD20 monoclonal antibody (rituximab), the patient achieved complete remission. Interestingly, Raynaud phenomenon disappeared under treatment and no new hemolytic events occurred. Anti-CD20 antibody treatment could be an attractive therapeutic approach for MCD, mainly when immune-related disorders are associated.     

Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection

BACKGROUND: Differences between studies in rates of severe hypoglycaemia in type 1 diabetic cohorts are common and poorly understood. The purpose of this study was to assess the frequency of severe hypoglycaemia in unselected patients treated in different secondary care centres and to evaluate the influence of risk markers, clinical setting and selection. METHODS: Cross-sectional Danish-British multicentre survey of 1076 consecutive adult patients with clinical type 1 diabetes who completed a detailed questionnaire on hypoglycaemia and related issues. Key variable was the self-reported rate of severe hypoglycaemia during the preceding year. RESULTS: The overall rate of severe hypoglycaemia in the preceding year was 1.3 episodes/patient-year and episodes were reported by 36.7% of subjects. The distribution was highly skewed with 5% of subjects accounting for 54% of all episodes. There were no significant differences between countries or centres. Reduced hypoglycaemia awareness, peripheral neuropathy and smoking were the only significant risk markers of severe hypoglycaemia in a stepwise multivariate analysis. In a subgroup selected to be similar to the Diabetes Control and Complications Trial (DCCT) cohort, the rate of severe hypoglycaemia was 0.35 episodes/patient-year and only retinopathy was a significant risk marker together with state of awareness. CONCLUSION: Severe hypoglycaemia remains a significant clinical problem in type 1 diabetes. The rate of severe hypoglycaemia and the influence of risk markers are very sensitive to selection and differences in rates between centres or studies seem to disappear after correction for differences in clinical characteristics. Smoking is a novel overall risk marker of severe hypoglycaemia.     

不稳定股骨转子间骨折不同内固定方法的疗效比较

目的 浅析不同内固定方法对不稳定股骨转子间骨折的疗效差异。方法 2009年1月至2013年5月行内固定手术的不稳定股骨转子间骨折患者36例,采用Gamma钉固定10例为A组,动力髋螺钉(DHS)固定11例为B组,股骨近端抗旋髓内钉(PFNA)固定15例为C组。对不同的内固定方式的术中出血量、手术时间、术后并发症、骨折愈合时间及髋关节功能评分等相关数据进行统计学分析。结果 各组患者术后均获随访,平均随访时间1年半,住院及随访期间无死亡病例。C组手术时间较A、B两组短,且有统计学意义(P<0.05)。B组术中出血量最多,愈合时间长,C组出血最少,但与A组比较差异无统计学意义(P>0.05)。术中A组发生股骨颈干角变小1例,髋内翻1例;B组发生髋内翻2例,头钉穿出1例,内固定松动1例;C组无相关并发症发生。骨折愈合时间A、B、C三组间比较差异无统计学意义(P>0.05)。A、C两组髋关节功能评分均较B组高,差异有统计学意义(P<0.05),但A、C两组间差异无统计学意义(P>0.05)。结论 PFNA是治疗不稳定股骨转子间骨折一个很好的选择,手术操作简便,损伤较小,出血少,固定牢靠,术后髋关节功能恢复较好,值得临床推广。     

Use of direct oral anticoagulants in antiphospholipid syndrome

Summary

The direct oral anticoagulants (DOACs) are therapeutic alternatives to warfarin and other vitamin K antagonists (VKAs), and constitute the standard of care for many indications. VKAs constitute the conventional therapy for the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS), but are often problematic, owing to the variable sensitivity of thromboplastins to lupus anticoagulant. Thus, the International Normalized Ratio may not accurately reflect anticoagulation intensity, or be clinically effective. Definition of the current role of DOACs in the treatment of APS is based on limited clinical trial data and information from other sources, including manufacturers’ data, case series or cohort studies, and expert consensus. The Rivaroxaban in Antiphospholipid Syndrome (RAPS) randomized controlled trial (RCT), which had a laboratory surrogate primary outcome measure, suggests that rivaroxaban has the potential to be an effective and convenient alternative to warfarin in thrombotic APS patients with a single venous thromboembolism event requiring standard‐intensity anticoagulation. However, further studies, in particular to provide better long‐term efficacy and safety data, are needed before it can be widely recommended. APS patients are clinically heterogeneous, with the risk of recurrent thrombosis and the intensity of anticoagulation being influenced by their clinical phenotype and risk profile. DOAC trials involving homogeneous thrombotic APS populations, with the antiphospholipid antibody status well defined, will help to optimize the appropriate treatment in APS patient subgroups. Ongoing and emerging DOAC RCTs should provide further information to guide the use of DOACs in APS patients. Optimal identification of APS patients is a key step in working towards improved therapeutic strategies in these individuals.

     

Analytical and between-subject variation of thrombin generation measured by calibrated automated thrombography on plasma samples*

Background: The Calibrated Automated Thrombography (CAT) is an in vitro thrombin generation (TG) assay that holds promise as a valuable tool within clinical diagnostics. However, the technique has a considerable analytical variation, and we therefore, investigated the analytical and between-subject variation of CAT systematically. Moreover, we assess the application of an internal standard for normalization to diminish variation.

Methods: 20 healthy volunteers donated one blood sample which was subsequently centrifuged, aliquoted and stored at ?80?°C prior to analysis. The analytical variation was determined on eight runs, where plasma from the same seven volunteers was processed in triplicates, and for the between-subject variation, TG analysis was performed on plasma from all 20 volunteers. The trigger reagents used for the TG assays included both PPP reagent containing 5?pM tissue factor (TF) and PPPlow with 1?pM TF. Plasma, drawn from a single donor, was applied to all plates as an internal standard for each TG analysis, which subsequently was used for normalization.

Results: The total analytical variation for TG analysis performed with PPPlow reagent is 3–14% and 9–13% for PPP reagent. This variation can be minimally reduced by using an internal standard but mainly for ETP (endogenous thrombin potential). The between-subject variation is higher when using PPPlow than PPP and this variation is considerable higher than the analytical variation.

Conclusion: TG has a rather high inherent analytical variation but considerable lower than the between-subject variation when using PPPlow as reagent.