CML treatment with tyrosine kinase inhibitors (TKIs) has improved many patients' prognosis, but during the disease's terminal phase, the blast crisis (CML-BC), has been disappointing. Allo-HSCT is another treatment, but survival rates are still disappointing. Currently, a combination of these two is suggested but with little evidence. This retrospective comparison reports on this combination and TKI alone for treatment of CML-BC. Of the 83 CML-BC patients, 45 received TKIs (imatinib; nilotinb or dasatinib after imatinib resistance; TKIs group) and 38 were treated with allo-HSCT after TKI (TKIs+allo-HSCT group). Treatment success was measured in terms of the hematologic, cytogenic and molecular responses, and subject outcome. Follow-up was 30-126 months or until death. Univariate and multivariate analyses determined EFS and OS predictors. Allo-HSCT significantly improved the 4-year OS (46.7 vs 9.7%, P o 0.001) and EFS (47.1 vs 6.7%, P o 0.001) compared to TKI treatment alone. Hemoglobin o 100 g/L, non-return to chronic phase after TKI therapy and TKI treatment alone are independent adverse predictors of OS and EFS. Allo-HSCT with individualized intervention after TKI therapy is superior to TKI alone for CML-BC.
Objective This study investigated whether the incidence of opportunistic infection differed in systemic lupus erythematosus patients who received different doses of corticosteroids. Methods We included patients with diagnosed systemic lupus erythematosus from 1997 to 2010 using Taiwan national health insurance data. The index day for systemic lupus erythematosus patients was 3 months after the systemic lupus erythematosus diagnosis. A non-steroid cohort was matched 4:1 with the steroid cohort according to age, sex and index day. The end of the follow-up period was the day of opportunistic infection diagnosis, 1 year after the index day, or death. Results The overall cumulative incidence of opportunistic infection was 136-fold higher in the steroid cohort than in the non-steroid cohort. The adjusted hazard ratio for developing mycobacterium infection in the steroid cohort was 11, and the adjusted hazard ratio for developing herpes zoster was 43.6 compared to the non-steroid cohort after adjusting for immunosuppressive agents and comorbidities. The adjusted hazard ratio value for opportunistic infection was 1.40 (95% confidence interval (CI) 0.78-2.51) for a daily prednisone-equivalent dose of 7.5-15 mg, 1.72 (95% CI 1.02-2.91) for 15-30 mg, 1.96 (95% CI 1.17-3.28) for 30-60 mg and 2.24 (95% CI 1.26-4.00) for over 60 mg compared with low-dose steroids (<7.5 mg). Conclusion This study confirmed that the risk of opportunistic infection is higher in systemic lupus erythematosus patients treated with steroids in the first 3 months after diagnosis versus those not treated with steroids. Medium and high doses were associated with a higher risk of opportunistic infection compared with low doses. However, there was no controlling for disease activity, making it hard to know if increases in infection were due to disease itself or corticosteroids.
35Monitor lizards are unique among ectothermic reptiles in that they have a high aerobic capacity 36 and distinctive cardiovascular physiology which resembles that of endothermic mammals. We 37 have sequenced the genome of the Komodo dragon (Varanus komodoensis), the largest extant 38 monitor lizard, and present a high resolution de novo chromosome-assigned genome assembly 39 for V. komodoensis, generated with a hybrid approach of long-range sequencing and single 40 molecule physical mapping. Comparing the genome of V. komodoensis with those of related 41 species showed evidence of positive selection in pathways related to muscle energy 42 metabolism, cardiovascular homeostasis, and thrombosis. We also found species-specific 43 expansions of a chemoreceptor gene family related to pheromone and kairomone sensing in V. 44 komodoensis and several other lizard lineages. Together, these evolutionary signatures of 45 adaptation reveal genetic underpinnings of the unique Komodo sensory, cardiovascular, and 46
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