A phase Ib/II study of xentuzumab, an IGF-neutralising antibody, combined with exemestane and everolimus in hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer.

Background: Xentuzumab-a humanised IgG1 monoclonal antibody-binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling and suppressing AKT activation by everolimus. This phase Ib/II exploratory trial evaluated xentuzumab plus everolimus and exemestane in hormone receptor-positive, locally advanced and/or metastatic breast cancer (LA/MBC).

Methods: Patients with hormone receptor-positive/HER2-negative LA/MBC resistant to non-steroidal aromatase inhibitors were enrolled.

Cardiovascular outcomes and LDL-cholesterol levels in EMPA-REG OUTCOME.

Objective: It is well established that higher low-density lipoprotein (LDL)-cholesterol levels are associated with increased cardiovascular risk. We analyzed whether effects of empagliflozin on cardiovascular outcomes varied by different LDL-cholesterol levels at baseline in EMPA-REG OUTCOME.

Methods: Participants with type 2 diabetes and high cardiovascular risk received empagliflozin (10/25 mg) or placebo in addition to standard of care.

SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials.

Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes mellitus (T2DM), it is likely that interventions to mitigate this risk must address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with apparent multiple effects. Inherent in their mode of action to decrease glucose reabsorption by the kidneys by increasing urinary glucose excretion, these agents improve glycaemic control independent of insulin secretion with a low risk of hypoglycaemia.

Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study.

Aims: To compare the efficacy, safety and tolerability of linagliptin or placebo administered for 24 weeks in combination with pioglitazone in patients with type 2 diabetes mellitus (T2DM) exhibiting insufficient glycaemic control (HbA1c 7.5-11.0%).

The exon 3-deleted/full-length growth hormone receptor polymorphism does not influence the effect of puberty or growth hormone therapy on glucose homeostasis in short non-growth hormone-deficient small-for-gestational-age children: results from a two-year controlled prospective study.

Context: The exon 3-deleted/full-length (d3/fl) GH receptor polymorphism (d3/fl-GHR) has been associated with responsiveness to GH therapy in short small-for-gestational-age (SGA) patients, although consensus is lacking. However, its influence on glucose homeostasis, at baseline or under GH therapy, has not been investigated.

Objective: Our objective was to evaluate whether the d3/fl-GHR genotypes influence insulin sensitivity in short SGA children before or after puberty onset or during GH therapy.

Children born small for gestational age (SGA) who fail to achieve catch up growth by 2-8 years of age are short from infancy to adulthood. Data from a cross-sectional study of 486 Spanish children.

Aims And Methods: Postnatal growth was evaluated in a cross-sectional study of 486 Spanish children, 241 girls and 245 boys, born small for gestational age (SGA), without height catch-up growth between the ages of 2 and 8 years [height <-2SD of age- and sex-matched controls born appropriate for gestational age (AGA)]. SGA was defined as birth weight and/or length values <-2SD of those of the born AGA control population. Weight and height values were grouped in 0.

Exon 3-deleted/full-length growth hormone receptor polymorphism genotype frequencies in Spanish short small-for-gestational-age (SGA) children and adolescents (n = 247) and in an adult control population (n = 289) show increased fl/fl in short SGA.

Context: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in genomic deletion of exon 3 has been associated with the degree of height increase in response to GH therapy.

Objective: The objective of the study was to evaluate the frequencies of d3/fl-GHR polymorphism genotypes in control and short small-for-gestational-age (SGA) populations.

Design: An adult control population with heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short non-GH-deficient SGA child population were selected.

The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH-deficient small-for-gestational-age children: results from a two-year controlled prospective study in 170 Spanish patients.

Context: The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted/full-length GHR) has recently been associated with responsiveness to GH therapy.

Objective: The objective of the study was to evaluate whether the d3/fl-GHR genotypes influence the intensity of spontaneous and/or GH therapy-stimulated growth in small-for-gestational-age (SGA) patients.

Design: This was a 2-yr prospective, controlled, randomized trial.

Longitudinal study of the pubertal growth spurt in children born small for gestational age without postnatal catch-up growth.

Most children born small for gestational age (SGA) experience extensive catch-up growth during the first months of life (87%) and by the age of 2 years only 13% are below -2 SDS for height. The long-term outcome, including pubertal growth spurt, of the subset of children born SGA without postnatal catch-up (SGAWPC) has been evaluated in very few surveys, and in none of them was the landmarks of puberty well described. Thus, a longitudinal study was conducted in these children throughout puberty since this is the only reliable way to accurately evaluate the pubertal growth spurt.

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults.

Objective: To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.

Patients And Design: Seventy-three patients with adult GH deficiency and organic hypothalamic-pituitary disease were recruited, along with 46 controls. The patients were divided into five groups according to the number of associated hormone deficiencies present.