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Aplastic anemia (AA) is a rare and serious disorder of hematopoietic stem cells (HSCs) that results in the loss of blood cells due to the failure of the bone marrow (BM). Although BM transplantation is used to treat AA, its use is limited by donor availability. In this sense, mesenchymal stem cells (MSCs) can offer a novel therapeutic approach for AA. This is because the MSCs contribute to the hematopoietic niche organization through their repopulating. In our study, we used the human immature dental pulp stem cell (hIDPSC), an MSC-like cell, to explore an alternative therapeutic approach for AA. For this, isogenic C57BL/6 mice were exposed to total body irradiation (TBI) to induce the AA. After 48 h of TBI, the mice were intraperitoneally treated with hIDPSC. The immunohistochemistry analyses confirmed that the hIDPSCs migrated and grafted in the mouse bone marrow (BM) and spleen, providing rapid support to hematopoiesis recovery compared to the group exposed to radiation, but not to those treated with the cells as well as the hematological parameters. Six months after the last hIDPSC transplantation, the BM showed long-term stable hematopoiesis. Our data highlight the therapeutic plasticity and hematoprotective role of hIDPSC for AA and potentially for other hematopoietic failures. [ABSTRACT FROM AUTHOR]

Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA. [ABSTRACT FROM AUTHOR]

AbstractBackground:This study investigated the risk of new-onset diabetes (NOD) among hypertensive patients initiating carvedilol therapy vs other beta-blocker (BB) therapy in a clinical practice setting.Methods:Patients aged ≥18 years with ≥1 pharmacy claim for a BB of interest (carvedilol immediate-release [IR]/controlled-release [CR], atenolol, metoprolol succinate, or metoprolol tartrate) were identified in the IMS LifeLink Health Plan Claims Database. Index date was the first chronologically occurring prescription for any BB during the enrollment period (July 1, 2000––December 31, 2007). Patients had to be continuously eligible to receive healthcare services 6 months prior to and a minimum of 3 months after index date and have ≥1 diagnostic code for hypertension (ICD-9-CM: 401.xx––405.xx) during this time frame. Patients were excluded for having a diagnosis of diabetes mellitus (ICD-9-CM: 250.xx) and/or prescription for antidiabetic therapy in the 6 months prior to and/or 3 months after index date. Eligible patients were propensity-score matched in a 1:3 ratio (carvedilol  :  other BBs). Mean duration of follow-up was 12.8 and 14.8 months for the carvedilol group and other BB group, respectively. Primary outcome of interest was presence and timing of NOD.Results:Among 3084 patients in the carvedilol group and 9252 in the other BB group, mean age was 56 years, with 54% male. NOD rate was 3.16 per 100 person-years for carvedilol patients vs 3.36 for patients in the other BB group (NS). Risk of NOD was similar between groups (HR 0.971, 95% CI: 0.78, 1.21; P  =  0.792).Conclusions:Findings suggest the risk of NOD among hypertensive patients is similar between carvedilol and other BB agents (i.e., atenolol, metoprolol succinate, or metoprolol tartrate).Limitations:The use of administrative claims data and relatively short follow-up period may limit the generalizability of results. [ABSTRACT FROM AUTHOR]

AbstractObjective:Although the choice of starting insulin for people with type 2 diabetes mellitus (T2DM) is often a basal or premix insulin analog, there is little evidence to base this decision on. This analysis aimed to determine if measurable clinical characteristics prior to starting insulin could predict differences in improved glycemic control between these options.Research design and methods:A thorough literature search was performed for treat-to-target studies in insulin-naïve individuals with T2DM treated with biphasic insulin aspart (BIAsp 30), a basal insulin analog (insulin glargine or insulin detemir) or NPH insulin regimens once or twice daily plus oral glucose-lowering drugs (OGLDs). Patient data were pooled and mean baseline age, diabetes duration, gender, body mass index (BMI), HbA1c, fasting plasma glucose (FPG), average postprandial plasma glucose over three meals (PPG) and bedtime PG were investigated for prediction of improved HbA1c, FPG or PPG. Statistical analyses employed a linear mixed model with insulin type, OGLD, time and time-squared as fixed effects and patient and trial as random effects.Results:Baseline age (p0.022) and bedtime PG (p0.036) were inter-related predictors of HbA1c. In older individuals with higher bedtime PG, BIAsp 30 appeared to be more beneficial. In contrast, basal insulin appeared to be a better choice in younger individuals with lower bedtime PG. For FPG, BMI (p0.011) and post-breakfast PG (p0.042) were identified as predictors. Basal insulin appeared to achieve better FPG in patients with lower BMI and higher post-breakfast PG, while BIAsp 30 appeared to be better in patients with higher BMI and lower post-breakfast PG. Age (p0.0347) was the only baseline characteristic associated with differences in average PPG: mean PPG was similar between regimens in younger people, but BIAsp 30 achieved better PPG results in older persons. Minor hypoglycemia was reported by 56 of BIAsp 30- and 45 of basal-treated individuals. The major limitation of the study was that only Novo Nordisk trials were included in the analysis as access to individual patient data was required. As the trials were fairly heterogeneous a strict methodology was used to minimize potential confounding factors.Conclusions:Premix analog rather than basal insulin may be an appropriate choice to target HbA1cvalues in older individuals and those with higher bedtime PG, while basal insulin may be more appropriate to target FPG in patients with lower BMI and higher post-breakfast PG. [ABSTRACT FROM AUTHOR]

AbstractObjective:To assess the association between pre-existing metabolic syndrome and health outcomes among veterans with schizophrenia.Methods:The Veterans Integrated Service Network 16 data (VISN16) for 10/2002 – 08/2005 were used to identify patients (n  593) with schizophrenia (ICD-9 codes: 250.xx) who were switched to a new antipsychotic agent in response to metabolic monitoring as part of a VISN 16 metabolic monitoring program. Two groups (patients with pre-existing metabolic syndrome [MetSyn] and without [MetSyn−]) were compared on resource utilization, antipsychotic adherence (medication possession ratio: MPR) and persistence (time to all-cause discontinuation of the switched antipsychotic) over 1 year.Results:About one-third of the patients who have undergone metabolic monitoring before the medication switch (35.2) had metabolic syndrome. The two groups did not significantly differ on healthcare resource utilization, MPR, or time to all-cause medication discontinuation. Adherence and persistence levels were relatively poor for both groups (mean MPR  0.33 for MetSyn; MPR  0.38 for MetSyn−). The median time to all-cause medication discontinuation was 50 days for both groups.Conclusions:In this retrospective study of patients with schizophrenia, the presence of pre-existing metabolic syndrome did not appear to impact patients’ healthcare resource utilization or their adherence and persistence with antipsychotic medication. [ABSTRACT FROM AUTHOR]