Anemia in older adults as a geriatric syndrome: A review

Anemia, a frequently occurring condition in older patients, has no standard definition; however, in most studies, it is defined as hemoglobin level <12 and <13 g/dL in women and men, respectively. Approximately 10% of older adults living in the community have anemia. The prevalence of anemia is significantly correlated with advanced age and male sex. Anemia is associated with falls, frailty and other negative outcomes, including early mortality. However, there remains little consensus regarding whether anemia treatment favorably affects these adverse outcomes. Therefore, this article reviews the prevalence of anemia, and provides updates on its common causes and treatments in older adults. While excluding well-established hematopoietic diseases, the etiology of anemia in older adults has been grouped into four categories: (i) nutritional deficiency; (ii) inflammation; (iii) clonal hematopoiesis; and (iv) “unexplained anemia,” when there is no clear mechanism to account for the anemia. Recently, clonal leukocytes were detected in a considerable number of older individuals. The number of somatic mutations in blood leukocytes increases with age; however, single mutations of DNMT3A, TET2 and ASXL1 are not correlated with the presence of unexplained anemia in older adults. With an increased understanding of anemia etiology and the availability of innovative anti-anemic drugs, future studies that evaluate the causes and benefits of treatment are required. Geriatr Gerontol Int 2021; 21: 549–554 .     

Imatinib-induced pancreatic hypertrophy in patients with gastrointestinal stromal tumor: Association with overall survival

ObjectivesTo investigate the frequency of imatinib-induced pancreatic complications and determine whether these are survival prognostic factors in patients with gastrointestinal stromal tumor (GIST).MethodsThis retrospective multicenter study included patients with histopathologically diagnosed GIST treated with imatinib who underwent computed tomography (CT) within 100 days before (pretreatment CT) and 500 days after (post-treatment CT) imatinib initiation (January 2004–December 2019). Forty-eight patients (63.0 ± 12.1 years, 30 men) were included. Two blinded radiologists independently measured pancreatic volumes. Pancreatic volume on pretreatment CT was compared with that of the control (within 1 year prior to pretreatment CT) and the first two post-treatment CTs using paired t-tests. Thresholds for pancreatic hypertrophy and atrophy were defined using a log-rank test. The prognostic importance of pancreatic hypertrophy was further analyzed using multivariate Cox proportional hazard regression models.ResultsPancreatic volume was significantly higher for the first post-treatment CT than pretreatment CT (71.5 cm³ vs. 67.4 cm³, P = .027), whereas no significant difference was observed between the pretreatment and control CTs. Optimal thresholds for pancreatic hypertrophy and atrophy were defined as an 22% increase and 30% decrease and found in 20 and three patients, respectively. Pancreatic hypertrophy was significantly associated with reduced survival [hazard ratio = 2.9 (95% confidence interval, 1.3–6.5), P = .0088]. No patients showed serum lipase elevation, nor were they suspected of having acute pancreatitis.ConclusionThere was frequent asymptomatic pancreatic swelling in patients with GIST after imatinib treatment, and a ≥22% increase in pancreatic volume was a predictor of reduced survival.     

Structure-Guided Design of Novel l-Cysteine Derivatives as Potent KSP Inhibitors

l-cysteine derivatives as selective KSP inhibitors. Here, we report further optimizations using docking modeling in the L5 allosteric binding site, which led to the discovery of several high affinity derivatives with two fused phenyl rings in the trityl group giving low nanomolar range KSP ATPase inhibition. The representative derivatives potently inhibited cell growth of HCT116 cells in correlation with KSP inhibitory activities and significantly suppressed tumor growth in the xenograft model in vivo.     

EPZ011989, A Potent,Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

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