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Study ObjectiveTo develop and validate a predictive model for glucose change and risk for new‐onset impaired fasting glucose in hypertensive participants following treatment with atenolol or hydrochlorothiazide (HCTZ).DesignRandomized multicenter clinical trial.PatientsA total of 735 white or African‐American men and women with uncomplicated hypertension.Measurements and Main ResultsPharmacogenomic Evaluation of Antihypertensive Responses (PEAR) is a randomized clinical trial to assess the genetic and nongenetic predictors of blood pressure response and adverse metabolic effects following treatment with atenolol or HCTZ. To develop and validate predictive models for glucose change, PEAR participants were randomly divided into a derivation cohort of 367 and a validation cohort of 368. Linear and logistic regression modeling were used to build models of drug‐associated glucose change and impaired fasting glucose (IFG), respectively, in the derivation cohorts. These models were then evaluated in the validation cohorts. For glucose change after atenolol or HCTZ treatment, baseline glucose was a significant (p<0.0001) predictor, explaining 13% of the variability in glucose change after atenolol and 12% of the variability in glucose change after HCTZ. Baseline glucose was also the strongest and most consistent predictor (p<0.0001) for development of IFG after atenolol or HCTZ monotherapy. The area under the receiver operating curve was 0.77 for IFG after atenolol and 0.71 after HCTZ treatment, respectively.ConclusionBaseline glucose is the primary predictor of atenolol or HCTZ‐associated glucose increase and development of IFG after treatment with either drug.

Four hundred and nine patients with chronic myelomonocytic leukemia (CMML) were included in the international collaborative study (268 (66%) and 141 (34%) from Mayo clinic and French consortium respectively). Thirty percent displayed an abnormal karyotype, including; 72% sole, 16% two, and 11% complex abnormalities. The most common abnormalities included; +8 (23%), ‐Y (20%), ‐7/7q‐(14%), 20q‐ (8%), +21 (8%), and der(3q) (8%). Patients with an abnormal karyotype were more likely to be elderly (P = 0.03), be anemic (P = 0.0009), have leukocytosis (P = 0.02) with neutrophilia (P = 0.03), demonstrate increased circulating immature myeloid cells (P = 0.0003), peripheral blood blasts (P < 0.0001), and bone marrow blasts (P < 0.0001). ASXL1 (P = 0.04) and SF3B1 (P = 0.03) mutations clustered with an abnormal karyotype, whereas SRSF2 (P = 0.02) mutations occurred more commonly with a normal karyotype. A step‐wise survival analysis resulted in three distinct cytogenetic risk categories: high (complex and monosomal karyotypes), intermediate (all abnormalities not in the high or low risk groups) and low [normal, sole ‐Y and sole der (3q)] with median survivals of 3 [hazard ratio (HR) = 8.1, 95% confidence interval (CI) = 4.6–14.2], 20 (HR = 1.7, 95% CI = 1.2–2.3) and 41 months, respectively. In multivariable analysis, this particular cytogenetic risk stratification remained significant in the context of the Molecular Mayo Model (P < 0.0001), MD Anderson prognostic model (P < 0.0001), the GFM CMML model (P < 0.0001) and was effective in predicting leukemic transformation (P = 0.004). Am. J. Hematol. 89:1111–1115, 2014. © 2014 Wiley Periodicals, Inc.

Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from cell therapy involving living metabolically active cells, either by treatment of their liver disease, or by prevention of their disease phenotype. Cell therapies, including hepatocyte transplantation and bioartificial liver (BAL) devices, have been proposed as therapeutic alternatives to the shortage of transplantable livers. Both BAL and hepatocyte transplantation are cellular therapies that avoid use of a whole liver. Hepatocytes are also widely used in drug screening and liver disease modelling. However, the demand for human hepatocytes, heavily outweighs their availability by conventional means. Induced pluripotent stem cells (iPSCs) technology brings together the potential benefits of embryonic stem cells (ESCs) (i.e., self-renewal, pluripotency) and addresses the major ethical and scientific concerns of ESCs: embryo destruction and immune-incompatibility. It has been shown that hepatocyte-like cells (HLCs) can be generated from iPSCs. Furthermore, human iPSCs (hiPSCs) can provide an unlimited source of human hepatocytes and hold great promise for applications in regenerative medicine, drug screening and liver diseases modelling. Despite steady progress, there are still several major obstacles that need to be overcome before iPSCs will reach the bedside. This review will focus on the current state of efforts to derive hiPSCs for potential use in modelling and treatment of liver disease.