Craniofacial bone atrophy in Parry Romberg syndrome demonstrated using a Bayesian hierarchical model

PurposeParry Romberg syndrome (PRS) is a condition characterized by progressive hemifacial atrophy, predominantly affecting the soft tissues. Associated bone retraction is a common clinical feature of PRS but has never been assessed. Here we used 3D imaging and Bayesian statistics in order to demonstrate and quantify bone atrophy in PRS.Materials and methodsTen non-operated patients with PRS (4/10 males) and 12 age-matched controls (7/12 males) were included into the study. The average age at CT-scan was 9.67 ± 4.13 years for PRS patients and 12.5 ± 4.37 years for controls. Soft and hard tissue atrophy levels were quantified using computed tomography scans, based on the distances between surfaces of the affected side and the non-affected contralateral side, both for the skin and the bone. We used a hierarchical Bayesian model with clinical priors in order to assess the relationship between hard and soft tissue atrophies.ResultsPRS patients had significant hard tissue atrophy, and atrophy extents were similar for soft and hard tissues. There was a trend for a correlation between the extent of hard tissue retraction and the extent of soft tissue retraction, and we could not demonstrate that the relationship between hard and soft tissue retractions was different in PRS and controls.ConclusionOur results indicated that bone atrophy was most probably a primary process rather than a phenomenon secondary to soft tissue retraction. We have provided the first assessment of bone atrophy in PRS patients using Bayesian statistics.     

Positioning sulphonylureas in a modern treatment algorithm for patients with type 2 diabetes: Expert opinion from a European consensus panel

The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second-line treatment after metformin and are often ranked at the same level as newer glucose-lowering medications. Strong evidence now shows that sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT-2is and GLP-1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT-2is and/or GLP-1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second-line agents continues to be acceptable in resource-constrained settings.     

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1?? resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.     

Clinical characteristics, sex hormones, and long-term follow-up in Swiss postmenopausal women presenting with Takotsubo cardiomyopathy

Background:

The overwhelming majority of patients with stress cardiomyopathy (SC) are postmenopausal women, suggesting an important pathophysiologic role of the female sex hormones. Preliminary data suggest that myocardial stunning might be provoked by estrogen deficiency.

Hypothesis:

We hypothesized that, compared with age‐ and gender‐matched patients with myocardial infarction (MI) or patients with normal coronary arteries, patients with SC would exhibit altered levels of sex hormones. Furthermore, we aimed to describe the clinical course and the pattern of sex hormones of the SC patients during long‐term follow‐up.

Methods:

Blood samples obtained on hospital admission were analyzed for estradiol (E2), progesterone (P), luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) in women with SC (n = 17), age‐matched women with acute MI (n = 16), and women with normal coronary arteries (n = 15). Six years after the initial event, SC patients underwent a clinical and echocardiographic follow‐up and reassessment of sex hormones.

Results:

Estrogen concentrations at hospital admission were significantly higher in the SC group compared with the MI and the control groups, with no difference in P, FSH, and LH concentrations. Follow‐up E2 after 6 years in SC patients was lower than during the acute SC episode. Follow‐up P in these patients was lower than P in the MI and control groups during the acute event, with a similar trend for E2. After a median follow‐up of 6.4 years, 1 sudden cardiac death occurred and 2 patients suffered from SC recurrence.

Conclusions:

During the acute event, E2 concentrations are elevated in postmenopausal SC patients compared with women with acute MI or with normal coronary arteries. The higher E2 concentrations might have exerted atheroprotective effects and thus diverted the stress response to SC rather than MI. Recurrence and/or sudden cardiac death remains a potential risk of SC. Clin. Cardiol. 2012 DOI: 10.1002/clc.21986 Roman Brenner, MD, and Daniel Weilenmann, MD, contributed equally to this work and should be considered first authors. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Vascular biomarkers in the prediction of clinical cardiovascular disease: the Strong Heart Study

We compared the ability of separately measured intimal-medial thickness and atherosclerotic plaque to predict incident cardiovascular disease. American Indian men and women from the Strong Heart Study who were free of cardiovascular disease were evaluated with carotid ultrasound and cardiovascular disease risk factor assessment. End-diastolic intimal-medial thickness of the common carotid arteries was measured and averaged. Arterial mass (cross-sectional area) was calculated from intimal-medial thickness and end-diastolic diameter. Atherosclerosis was defined by focal plaque (discrete thickening >50% relative to the adjacent wall) and the number of carotid segments containing plaque (plaque score); 2441 participants (age 63±8 years) were followed-up for a mean of 7.7±2.8 years, during which time 495 experienced incident cardiovascular disease events. Time-to-event analyses were performed in groups stratified according to diabetes and hypertension status. Cardiovascular disease events were predicted by presence and extent of atherosclerosis in all groups; intima-medial thickness and arterial mass were only associated with outcomes when neither hypertension nor diabetes was present. Unequivocal evidence of atherosclerosis (plaque) and its extent (plaque score) are independently associated with incident cardiovascular disease events in individuals without preexisting cardiovascular disease regardless of diabetes and hypertension status. Hypertension-related increases in intima-media thickness and arterial mass appear to limit their use as measures of early or diffuse atherosclerosis and, hence, association with cardiovascular disease outcomes. These findings support the utility of separate assessment of focal atherosclerosis and intimal-medial thickness in epidemiological studies, trials, and risk stratification protocols.