Importance of risk factor management in diabetic patients and reduction in Stage B heart failure

BACKGROUND: A number of studies have demonstrated the presence of a diabetic cardiomyopathy, increasing the risk of heart failure development in this population. Improvements in present-day risk factor control may have modified the risk of diabetes-associated cardiomyopathy.

AIM: We sought to determine the contemporary impact of diabetes mellitus (DM) on the prevalence of cardiomyopathy in at-risk patients with and without adjustment for risk factor control.

DESIGN: A cross-sectional study in a population at risk for heart failure.

METHODS: Those with diabetes were compared to those with other cardiovascular risk factors, unmatched, matched for age and gender and then matched for age, gender, body mass index, systolic blood pressure and low density lipoprotein cholesterol.

RESULTS: In total, 1399 patients enrolled in the St Vincent's Screening to Prevent Heart Failure (STOP-HF) cohort were included. About 543 participants had an established history of DM. In the whole sample, Stage B heart failure (asymptomatic cardiomyopathy) was not found more frequently among the diabetic cohort compared to those without diabetes [113 (20.8%) vs. 154 (18.0%), P = 0.22], even when matched for age and gender. When controlling for these risk factors and risk factor control Stage B was found to be more prevalent in those with diabetes [88 (22.2%)] compared to those without diabetes [65 (16.4%), P = 0.048].

CONCLUSION: In this cohort of patients with established risk factors for Stage B heart failure superior risk factor management among the diabetic population appears to dilute the independent diabetic insult to left ventricular structure and function, underlining the importance and benefit of effective risk factor control in this population on cardiovascular outcomes.

Development of release methods for critically endangered freshwater pearl mussels (Margaritifera margaritifera)

Biodiversity loss is a global problem with freshwater bivalves considered amongst the most
endangered biota. The freshwater pearl mussel, Margaritifera margaritifera, is declining
throughout its range owing to habitat degradation and overexploitation. In most of its range,
populations are regarded as reproductively non-functional which has led to the development
of captive breeding programmes. A novel method of releasing M. margaritifera was trialled,
with captive-bred juveniles being released into the rivers caged in ‘mussels silos’ (protective
concrete domes with ventilation creating upwelling to ensure water through flow). We
released 240 juvenile mussels and survival and growth rates were monitored for 18 months
post-release for three size classes: A (13.01-20.00mm); B (10.01-13.00mm); and C (4.01-
10.00mm). We explicitly tested two experimental treatments; one where sediment was added
to each silo (allowing mussels to orientate and burrow) and one without sediment. Survival
by the end of the experiment at month 18 was significantly higher for the largest size class at
97% (though growth was lowest in this cohort), and lowest for the smallest size class at 61%
(though growth was highest in this cohort). Survival and growth were unaffected by the
experimental treatment suggesting that adding sediment offered no advantage. Growth was
positively correlated with both water temperature and the particle size of suspended solids
(both of which were collinear, peaking in summer). There are a large number of ex situ
breeding programmes for freshwater pearl mussels throughout Europe and our finding
suggest that the use of ‘mussel silos’ could be a useful tool to protecting juvenile mussels
allowing them to be released at a relatively early stage of development, minimising the risk of
domestication.

Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms.

The mechanisms involved in the progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) to malignant multiple myeloma (MM) and plasma cell leukemia (PCL) are poorly understood but believed to involve the sequential acquisition of genetic hits. We performed exome and whole-genome sequencing on a series of MGUS (n=4), high-risk (HR)SMM (n=4), MM (n=26) and PCL (n=2) samples, including four cases who transformed from HR-SMM to MM, to determine the genetic factors that drive progression of disease. The pattern and number of non-synonymous mutations show that the MGUS disease stage is less genetically complex than MM, and HR-SMM is similar to presenting MM. Intraclonal heterogeneity is present at all stages and using cases of HR-SMM, which transformed to MM, we show that intraclonal heterogeneity is a typical feature of the disease. At the HR-SMM stage of disease, the majority of the genetic changes necessary to give rise to MM are already present. These data suggest that clonal progression is the key feature of transformation of HR-SMM to MM and as such the invasive clinically predominant clone typical of MM is already present at the SMM stage and would be amenable to therapeutic intervention at that stage.