Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia

In β-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by β-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized by limited erythroid cell differentiation. In thalassemic mice, we observed that a greater than normal percentage of erythroid cells was in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle–promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, and Ki-67 and the antiapoptotic protein Bcl-X_L. The cells also differentiated less than normal erythroid ones in vitro. To investigate whether Jak2 could be responsible for the limited cell differentiation, we administered a Jak2 inhibitor, TG101209, to healthy and thalassemic mice. Exposure to TG101209 dramatically decreased the spleen size but also affected anemia. Although our data do not exclude a role for apoptosis in IE, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates IE in thalassemia. In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.     

A prospective open study of the efficacy of high-dose recombinant hepatitis B rechallenge vaccination in HIV-infected patients

Double-dose hepatitis B virus revaccination of human immunodeficiency virus (HIV)-infected patients proved to be effective in 50.7% of 144 patients who had previously failed to respond to standard doses. In the multivariate analysis, female patients were found to have a significantly better response (P= .03). The effect of age on the response depended on the viral load at the time of revaccination. For patients with a detectable HIV RNA load, the effect of age was stronger (odds ratio [OR], 0.34 per 10 years older [95% confidence interval {CI}, 0.16-0.72]; P= .005) than for patients with an undetectable HIV RNA load (OR, 0.74 per 10 years older [95% CI, 0.50-1.09]; P= .12).     

Monoclonal Antibody Biosimilars in Oncology: Critical Appraisal of Available Data on Switching

Purpose

With the introduction of biosimilars of anticancer monoclonal antibodies (mAbs) in oncology, physicians are potentially confronted with the question whether it is clinically adequate to switch patients who are clinically stable on treatment with the reference product to a newly available biosimilar (or vice versa/from 1 biosimilar to another). For a proper impact assessment of switching, robust, product-specific, and clinically relevant evidence should be required, ideally including data from appropriately designed switching studies. In this article, we assess the current body of switching data available for approved or proposed biosimilars of anticancer mAbs.

Choroidal Neovascularization Associated with Punctate Inner Choroidopathy: Combination of Intravitreal Anti-VEGF and Systemic Immunosuppressive Therapy

Purpose

Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported.

Case Report

A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed.

Results

Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again.

Conclusion

Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC.Key Words: Punctate inner choroidopathy, Choroidal neovascularization, Intravitreal anti-VEGF therapy, Choroiditis     

Role of prothrombin 19911 A>G polymorphism,blood group and male gender in patients with venous thromboembolism: Results of a German cohort study

Journal of Thrombosis and Thrombolysis - The role of the A>G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism...     

The effect of glucose dynamics on plasma copeptin levels upon glucagon,arginine, and macimorelin stimulation in healthy adults

Pituitary - Non-osmotic stimulation tests using glucagon, arginine, or macimorelin were recently evaluated for their ability to assess posterior pituitary function. Glucagon and arginine, but not...