Impact of Donor Age on the Osteogenic Supportive Capacity of Mesenchymal Stromal Cell-Derived Extracellular Matrix.

Mesenchymal stromal cells (MSC) have been proposed as an emerging cell-based therapeutic option for regenerative medicine applications as these cells can promote tissue and organ repair. In particular, MSC have been applied for the treatment of bone fractures. However, the healing capacity of these fractures is often compromised by patient's age. Therefore, considering the use of autologous MSC, we evaluated the impact of donor age on the osteogenic potential of bone marrow (BM)-derived MSC. MSC from older patients (60 and 80 years old) demonstrated impaired proliferative and osteogenic capacities compared to MSC isolated from younger patients (30 and 45 years old), suggesting that aging potentially changes the quantity and quality of MSC. Moreover, in this study, we investigated the capacity of the microenvironment [i.e., extracellular matrix (ECM)] to rescue the impaired proliferative and osteogenic potential of aged MSC. In this context, we aimed to understand if BM MSC features could be modulated by exposure to an ECM derived from cells obtained from young or old donors. When aged MSC were cultured on decellularized ECM derived from young MSC, their in vitro proliferative and osteogenic capacities were enhanced, which did not happen when cultured on old ECM. Our results suggest that the microenvironment, specifically the ECM, plays a crucial role in the quality (assessed in terms of osteogenic differentiation capacity) and quantity of MSC. Specifically, the aging of ECM is determinant of osteogenic differentiation of MSC. In fact, old MSC maintained on a young ECM produced higher amounts of extracellularly deposited calcium (9.10 ± 0.22 vs. 4.69 ± 1.41 µg.µl-1.10-7 cells for young ECM and old ECM, respectively) and up-regulated the expression of osteogenic gene markers such as Runx2 and OPN. Cell rejuvenation by exposure to a functional ECM might be a valuable clinical strategy to overcome the age-related decline in the osteogenic potential of MSC by recapitulating a younger microenvironment, attenuating the effects of aging on the stem cell niche. Overall, this study provides new insights on the osteogenic potential of MSC during aging and opens new possibilities for developing clinical strategies for elderly patients with limited bone formation capacity who currently lack effective treatments.

Clinical outcomes of AML patients treated with Azacitidine in Portugal: A retrospective multicenter study.

Retrospective data was collected from 77 elderly acute myeloid leukemia (AML) patients treated with Azacitidine (AZA) and 50 elderly AML patients treated with intensive chemotherapy (IC) from 4 Portuguese Hospitals. Median OS was 10.6 months in those receiving AZA as 1st line. Response (overall response rate 44%) had a significant impact on overall survival (p=<0.0001). Median OS of the comparator IC cohort was significantly inferior to that observed in the cohort treated with AZA in first line (p=0.0104). These results support the efficacy of AZA in AML in the elderly in any line of treatment.

Clonal Hypereosinophilia with ETV6 Rearrangement Evolving to T-Cell Lymphoblastic Lymphoma: A Case Report and Review of the Literature.

Hypereosinophilia, either clonal or reactive, has been described in association with multiple hematological malignancies. We describe a case of a patient presenting with hypereosinophilia that evolved into T-cell lymphoblastic lymphoma. Complete remission was achieved with chemotherapy; however, hypereosinophilia recurred 5 months later in association with myeloblastic bone marrow infiltration and without evidence of lymphoblastic lymphoma relapse. Cytogenetic analysis of the bone marrow showed a complex translocation involving chromosomes 7, 12, and 16. A rearrangement of ETV6 gene (12p13) was demonstrated by FISH studies, thus confirming the clonality of this population. The association of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia has been described in disorders with FGFR1 rearrangements. We hypothesize that other clonal eosinophilic disorders lacking this rearrangement could behave in a similar fashion through different pathogenic mechanisms.

[Co-morbidity and functionality: observational study of a cohort of patients]. / Comorbilidade e funcionalidade: estudo observacional de um coorte de doentes.

Hypertension, Diabetes Mellitus, Cardiac Ischemic Disease and Asthma are chronic diseases that often coexist. Studies on consequences of co-morbidity conclude that the competition of illnesses can be associated with physical and social disability and a higher request of Health services. This study intends to describe the alterations in co-morbidity of a cohort of sick people between 2003 and 2007, to relate it with functionality and to characterise their impact on health resources. The study is observational. A random sample of 110 sick people, stratified by age and gender, was obtained from the database COMORB4DC. Variables were studied on specific domains: demographic, social, morbid-mortality, health resources and functionality. Health problems are classified according to ICPC2. The test of marginal homogeneity, the test of the signals, the test of Mann-Whitney and the test of Kruskal-Wallis were used for statistically analysis. The majority of the sample has 65 or more years. The most frequent comorbidities between the four chronic index diseases, in the years of 2003 and 2007, are hypertension with diabetes and the hypertension with ischemic cardiac disease. In the set of the locomotion tasks, physical and instrumental autonomy, only 8% of the sick people are totally independent and 47% are autonomous, these mainly had to use ways of support. Between 2003 and 2007, it is verified a difference (p < 0.001) in the average of identified health problems and in the number of problems grouped in classes. The dependence in locomotion is only associated with a superior number of illnesses (p = 0.033), of used resources of health (p = 0.005) and prescribed drugs (p = 0.001). It is verified to exist a correlation among the number of chronic diseases and the number of contacts with the health centre (r = 0.434, p < 0.001). The collected data on co-morbidity, functionality, resource to social assistance activities and medication allow us to better know the complex network of co-morbidity. This can help us make earlier diagnosis, more accurate prognosis and creating health quality and management plans. The repetition of the study with another interval of time can give us more knowledge on this net of relations. It is essential to effectively provide population with specific health resources and to link primary, secondary and tertiary care.