T Cells Redirected to EphA2 for the Immunotherapy of Glioblastoma

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.     

Impact of pharmacy outreach services on blood pressure management in the elderly community of Hong Kong

Aim: To investigate the impact of the Pharmacy Outreach Service (POS) on blood pressure (BP) and disease knowledge among community‐dwelling elderly patients with hypertension, and to evaluate the sustainability of such impact of POS. Methods: A prospective open‐labeled study of elderly adults (aged ≥65 years) with hypertension (BP ≥140/90 mmHg for non‐diabetics and ≥130/80 mmHg for diabetics) was carried out at seven elderly community centers from July 2008 to March 2010. Pharmacists provided BP monitoring, medication review and disease knowledge assessment. The target BP was <140/90 mmHg for non‐diabetics and <130/80 mmHg for diabetics. The primary outcome was BP change, whereas the secondary outcome was the change of disease knowledge of hypertension. All outcomes were compared between baseline and the last visit. For POS 2008/09 participants, BP was compared between values obtained during POS 2008/09 and 2009/10. Results: A total of 97 participants were recruited. Systolic BP reduced significantly from 152.38 ± 18.80 mmHg to 147.04 ± 20.72 mmHg (P = 0.021), and diastolic BP reduced from 73.84 ± 11.36 mmHg to 71.03 ± 10.97 mmHg (P = 0.010). Cumulative reductions in mean systolic BP and diastolic BP throughout the 2‐year study period were 21.39 ± 24.72 mmHg and 9.88 ± 13.48 mmHg, respectively (P < 0.001). A 12% increase in the at‐goal rate was observed in new participants recruited in 2009 (P = 0.039). Disease knowledge of hypertension improved significantly (P < 0.005), particularly in areas that included the definition of hypertension, diet and lifestyle modification. Conclusions: The POS might improve blood pressure control, hypertension and diabetes knowledge in elderly adults with hypertension in Hong Kong. The effect on blood pressure improvement was sustainable. Geriatr Gerontol Int 2013; 13: 175–181.     

胫股关节吻合性对人工膝关节聚乙烯磨损的影响

人工关节置换术是矫正关节畸形、解除关节疼痛、重建关节功能的主要手段。多年来 ,人工全髋、全膝皆以聚乙烯为关节形成表面 ,随着人工关节置换的广泛开展 ,聚乙烯磨损问题越来越引起人们的关注。聚乙烯磨损及其产生的碎屑和磨损颗粒所引发的生物学反应及导致的骨吸收、骨溶解 ,是造成假体松动、人工关节翻修的主要原因[1,2 ] 。与人工髋关节的球洞几何形态相比 ,人工膝关节的几何形态要不吻合的多 ,胫骨假体表面常承受较大的接触应力 ,较易产生磨损[2 ,3 ] ,理论上关节形成表面越吻合 ,聚乙烯磨损越少 ,不同的胫股关节吻合性 ,对假体磨损产…     

Pharmacological and Non Pharmacological Strategies in the Management of Coronary Artery Disease and Chronic Kidney Disease

Patients with advanced chronic kidney disease (CKD), including those treated with dialysis, are at high risk for the development of cardiovascular disease (CVD). CVD accounts for 45-50% of deaths among dialysis patients. Therapy of acute and chronic coronary heart disease (CHD) that is effective in the general population is frequently less effective in patients with advanced CKD. Drug therapy in such patients may require dose modification in some cases. Oral anti-platelet drugs are less effective in those with advanced CKD than in persons with normal or near normal renal function. The intravenous antiplatelet drugs eptifibatide and tirofiban both require dose reductions in patients with advanced CKD. Enoxaparin requires dose reduction in early stage CKD and is contraindicated in hemodialysis patients. Unfractionated heparin and warfarin maybe used without dose adjustment in CKD patients. Atenolol, acetbutolol and nadolol may require dose adjustments in CKD. Metoprolol and carvedilol do not. Calcium channel blockers and nitrates do not require dose adjustment, whereas ranolazine does. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers may safely be used in CKD patients with close observation for hyperkalemia. The safety of spironolactone in such patients is questionable. Statins are less effective in reducing cardiovascular complication in CKD patients and their initiation is not recommended in dialysis patients. Coronary artery bypass grafting is associated with higher short-term mortality, but better long-term morbidity and mortality than percutaneous coronary interventions in patients with advanced CKD with non-ST segment ACS and chronic CHD.     

Acute ischemic syndromes. Adjunctive therapy

The acute coronary syndromes (ACS) represent a heterogeneous group of patients along a continuum of risk from unstable angina to non-ST-segment elevation myocardial infarction. ACS is a term that has been used to describe the constellation of clinical symptoms that represent acute myocardial ischemia. This article reviews the adjunctive medications that are used during emergency cardiovasculare care for the early management of patients experiencing the ACS. The adjunctive therapies are divided into early immediate treatment and then subsequent management in the acute care setting.