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Primary myelofibrosis is characterized by clonal myeloproliferation, dysmegakaryopoiesis, extramedullary hematopoiesis associated with myelofibrosis and altered stroma in the bone marrow and spleen. The expression of CD9, a tetraspanin known to participate in megakaryopoiesis, platelet formation, cell migration and interaction with stroma, is deregulated in patients with primary myelofibrosis and is correlated with stage of myelofibrosis. We investigated whether CD9 participates in the dysmegakaryopoiesis observed in patients and whether it is involved in the altered interplay between megakaryocytes and stromal cells. We found that CD9 expression was modulated during megakaryocyte differentiation in primary myelofibrosis and that cell surface CD9 engagement by antibody ligation improved the dysmegakaryopoiesis by restoring the balance of MAPK and PI3K signaling. When co-cultured on bone marrow mesenchymal stromal cells from patients, megakaryocytes from patients with primary myelofibrosis displayed modified behaviors in terms of adhesion, cell survival and proliferation as compared to megakaryocytes from healthy donors. These modifications were reversed after antibody ligation of cell surface CD9, suggesting the participation of CD9 in the abnormal interplay between primary myelofibrosis megakaryocytes and stroma. Furthermore, silencing of CD9 reduced CXCL12 and CXCR4 expression in primary myelofibrosis megakaryocytes as well as their CXCL12-dependent migration. Collectively, our results indicate that CD9 plays a role in the dysmegakaryopoiesis that occurs in primary myelofibrosis and affects interactions between megakaryocytes and bone marrow stromal cells. These results strengthen the "bad seed in bad soil" hypothesis that we have previously proposed, in which alterations of reciprocal interactions between hematopoietic and stromal cells participate in the pathogenesis of primary myelofibrosis., (Copyright© Ferrata Storti Foundation.)

Background: Necrotising retinopathy in immunocompromised hosts is characterised by an unfavourable course often with unspecific clinical features. Therefore, differential diagnosis can be critical., History and Signs: A case of an initially therapy-resistant, necrotizing retinopathy is presented in a 65-year-old immunocompromised male patient suffering from chronic B-cell leukemia., Therapy and Outcome: Despite demonstration of cytomegalovirus and Varicella-Zoster-Virus DNA by polymerase chain reaction in vitreous, aqueous humour samples and from retinal biopsy with specific antiviral therapy, a progression of retinal necrosis was noted. Finally Toxoplasma gondii DNA was detected and retinal necrosis resolved after specific treatment. However, visual acuity remains poor because of optic nerve atrophy., Conclusions: The polymerase chain reaction is an important diagnostic tool for differential diagnosis in immunocompromised patients suffering from necrotising retinopathy. If resistance to therapy is noted atypical ocular toxoplasmosis should be considered. The presented case report shows that even multiple infections are possible in the same host.

Background: To evaluate the potential role of radial optic neurotomy (RON), a new surgical technique has been recently proposed for treating central retinal vein occlusion (CRVO). It is hypothesized that CRVO constitutes a neurovascular compartment syndrome at the site of the lamina cribrosa, which can be alleviated by performing a radial incision at the nasal part of the optic nerve head, relaxing the cribriform plate and the adjacent sclera., Methods: One hundred and seven patients were treated with RON for CRVO at five collaborating ophthalmologic centers. All patients were evaluated by a standardized protocol. For analysis of the angiographic and fundus findings, reference images were used. Intraoperative and postoperative complications were reviewed., Results: On 55 right and 52 left eyes of 107 patients (55.6% male, 44.4% female) with a median age of 68 years (range 21-91 years), RON was performed. The median follow-up time was 6 months (range 1-24 months). The median preoperative visual acuity (VA) was 0.05 (logMAR 1.3), increasing to a median postoperative VA of 0.08 (logMAR 1.1). Patients with an interval of more than 90 days between RON and onset of CRVO showed no significant change in VA at the 6-month follow-up. Severe peripapillary swelling of the optic nerve head prior to RON resulted in an average increase of 4.2 lines in VA at the 6-month follow-up. Angiographic findings of shunt vessels were seen in 18/30 cases after 12 months and were accompanied by an average improvement of VA of six lines. Visual field tests showed various defects in 86.8% of all cases. In one patient an iatrogenic injury of the central retinal artery occurred (0.9%)., Conclusion: Despite the potential risk of visual field defects, RON seems to be a quite safe procedure. The majority of patients showed rapid normalization of the morphologic fundus findings, with an improvement in VA uncommon for the natural history of CRVO. No significant change in VA was seen in patients with an interval of more than 90 days between the onset of CRVO and RON. A prospective study is warranted for further investigation.