The landscape of novel strategies for acute myeloid leukemia treatment: Therapeutic trends, challenges, and future directions.

Acute myeloid leukemia (AML) is a highly heterogeneous subtype of hematological malignancies with a wide spectrum of cytogenetic and molecular abnormalities, which makes it difficult to manage and cure. Along with the deeper understanding of the molecular mechanisms underlying AML pathogenesis, a large cohort of novel targeted therapeutic approaches has emerged, which considerably expands the medical options and changes the therapeutic landscape of AML. Despite that, resistant and refractory cases caused by genomic mutations or bypass signalling activation remain a great challenge. Therefore, discovery of novel treatment targets, optimization of combination strategies, and development of efficient therapeutics are urgently required. This review provides a detailed and comprehensive discussion on the advantages and limitations of targeted therapies as a single agent or in combination with others. Furthermore, the innovative therapeutic approaches including hyperthermia, monoclonal antibody-based therapy, and CAR-T cell therapy are also introduced, which may provide safe and viable options for the treatment of patients with AML.

Late-onset depression in the absence of stroke: associated with silent brain infarctions, microbleeds and lesion locations.

BACKGROUND: Late-onset depression (LOD) is a frequent mood disorder among elderly. Previous studies have proved that LOD is associated with cerebral silent lesions especially white matter lesions (WML) and yielded the "vascular depression" hypothesis to explain the pathogenesis of LOD. However, there were relatively few studies about the association between silent brain infarctions (SBIs), microbleeds (MBs) and the prevalence of LOD. In this study we sought to evaluate the presence, accumulation and locations of SBIs and MBs, and explore the possible association between them and LOD. METHODS: 65 patients of LOD diagnosed according to DSM-IV and 270 subjects of control group were enrolled and scanned by MRI to analyze the presence, numbers and locations of SBIs and MBs. Clinical and radiological characteristics were compared between LOD patients and control group. Logistic regression models were constructed to identify the independent risk factors for LOD. RESULTS: LOD patients had higher prevalence and numbers of both SBIs and MBs. SBIs and MBs in the left hemisphere, SBIs in basal ganglia and lobar MBs were all independent risk factors for LOD. CONCLUSION: The presence of both SBIs and MBs were associated with a higher rate LOD. Lesions in some specific locations might be critical for the presence of LOD.

Depression in silent lacunar infarction: a cross-sectional study of its association with location of silent lacunar infarction and vascular risk factors.

Most previous studies reported a close link between fresh infarcts and post-stroke depression. However, studies on the relation of depression and silent lacunar infarction (SLI) are limited. This study aims to analyze the effects of SLI and the vascular risk factors on depression. A total of 243 patients with SLI were divided into depression and non-depression groups. The presence and location of SLI were evaluated with magnetic resonance imaging. Depression was assessed with the Patient Health Questionnaire-9 and vascular risks factors were collected. We used t tests and χ (2) test to compare the baseline characteristics of the two groups and the multivariate logistic regression model to identify the risk factors for depression. Univariate analysis results showed that the proportion of patients with SLI in basal ganglia was significantly higher in the depression group (65.0 versus 32.8 %; P < 0.001) than in the non-depression group, and multiple prevalent factors had significant differences between the two groups. However, on multivariate logistic analysis, some of these factors were eliminated, and SLI in basal ganglia remained an independent predictor of depression with an odds ratio of 3.128 (P = 0.018). In addition, vascular risk factors, including high body mass index level, presence of inflammation markers (e.g., CRP, TNF-α, Hs-CRP, and IL-6), and lack of physical activity, were associated with depression. Our findings suggest that SLI in basal ganglia is associated with a higher risk of depression. Vascular risk factors, which are intertwined, may propose the pathological basis of depression in SLI.

Vancomycin-induced thrombocytopenia in endocarditis: A case report and review of literature.

BACKGROUND: Thrombocytopenia is a serious complication in the medical practice of numerous drugs. Vancomycin is frequently used for the prophylaxis and treatment of suspected or identified methicillin-resistant positive infections. Several cases with vancomycin-induced thrombocytopenia (VIT) have been reported. However, these have rarely been extensively reviewed. The present report describes a case of VIT in endocarditis, and reviews all VIT cases reported in the literature. CASE SUMMARY: A 26-year-old male diagnosed with infective endocarditis was admitted. The patient was treated with multiple drugs, including vancomycin, which was initially intravenously given at 1000 mg every 12 h and subsequently at 500 mg every 8 h on day 3. On day 11, the platelet count decreased to 51 × 109/L, vancomycin was switched to 500 mg every 12 h, and platelet transfusion was given. On day 17, the platelet count dropped to 27 × 109/L, and platelet transfusion was administered again. On day 23, vancomycin was adjusted to 500 mg every 8 h as the trough concentration dropped to the minimum effective concentration. On day 33, the platelet count declined to approximately 40 × 109/L. After platelet transfusion, the platelet count rebounded to 90 × 109/L on day 35 but dropped again to 42 × 109/L on day 43. Based on the time-to-platelet count curve and Naranjo's Adverse Drug Reaction Probability Scale score, VIT was suspected. After vancomycin discontinuation and platelet transfusion, the platelet count gradually normalized. CONCLUSION: The diagnosis of VIT can be achieved through the time-to-platelet count curve and Naranjo's Adverse Drug Reaction Probability Scale score. The platelet count cannot be normalized simply by platelet transfusion alone, and vancomycin discontinuation is essential.

Impacts of climate change and human activities on net primary productivity of grasslands in Inner Mongolia, China during 1982-2015.

We analyzed the impacts of climate change and human activities on the net primary productivity of grasslands in Inner Mongolia during 1982-2015. The results showed that the growth rates of actual net primary productivity (ANPP) were 1.08 and 1.36 g C · m-2 · a-1 in 1982-1998 and 1999-2015, respectively. Such changes were largely due to restoration, with restoration implementing in 81.6% and 76.3% of the total study area in 1982-1998 and 1999-2015, respectively. The area of degraded grasslands tends to increase. The effects of climate change and human activity varied across different types of grassland. Climate change was the main contributor to grassland restoration over the two periods, with the contribution rates being 79.3% and 94.1%, respectively. The ANPP was positively correlated with precipitation but not with temperature, indicating that precipitation was the main climate factor influencing grassland restoration. Human activities contributed most to grassland degradation over the two periods, with the contribute rate being 83.3% and 87.8%, respectively. Our results suggested that the climate change was the dominant contributor to grassland restoration, while human activities, such as increase in livestock numbers, cultivation and afforestation, accelerated grassland degradation.