In‐Series Versus In‐Parallel Mechanical Circulatory Support for the Right Heart: A Simulation Study

Right heart failure (RHF) is a serious health issue with increasing incidence and high mortality. Right ventricular assist devices (RVADs) have been used to support the end‐stage failing right ventricle (RV). Current RVADs operate in parallel with native RV, which alter blood flow pattern and increase RV afterload, associated with high tension in cardiac muscles and long‐term valve complications. We are developing an in‐series RVAD for better RV unloading. This article presents a mathematical model to compare the effects of RV unloading and hemodynamic restoration on an overloaded or failing RV. The model was used to simulate both in‐series (sRVAD) and in‐parallel (pRVAD) (right atrium‐pulmonary artery cannulation) support for severe RHF. The results demonstrated that sRVAD more effectively unloads the RV and restores the balance between RV oxygen supply and demand in RHF patients. In comparison to simulated pRVAD and published clinical and in silico studies, the sRVAD was able to provide comparable restoration of key hemodynamic parameters and demonstrated superior afterload and volume reduction. This study concluded that in‐series support was able to produce effective afterload reduction and preserve the valve functionality and native blood flow pattern, eliminating complications associated with in‐parallel support.     

Elevated serum creatinine and low albumin are associated with poor outcomes in patients with liposarcoma

Low serum albumin levels and impaired kidney function have been associated with decreased survival in patients with a variety of cancer types. In a retrospective cohort study, we analyzed 84 patients with liposarcoma treated at from May 1994 to October 2011. Uni‐ and multivariable Cox proportional hazard models and competing risk analyses were performed to evaluate the association between putative biomarkers with disease‐specific and overall survival. The median age of the study population was 51.7 (range 19.6–83.8) years. In multivariable analysis adjusted for AJCC tumor stage, serum creatinine was highly associated with disease‐specific survival (Subdistribution Hazard ratio (SHR) per 1 mg/dl increase = 2.94; 95%CI 1.39–6.23; p = 0.005). High albumin was associated with improved overall and disease‐specific survival (Hazard Ratio (HR) per 10 units increase = 0.50; 95%CI 0.26–0.95; p = 0.033 and SHR = 0.64; 95%CI 0.42–1.00; p = 0.049). The serum albumin‐creatinine‐ratio emerged to be associated with both overall and disease‐specific survival after adjusting for AJCC tumor stage (HR = 0.95; 95%CI 0.92–0.99; p = 0.011 and SHR = 0.96; 95%CI 0.93–0.99; p = 0.08). Our study provides evidence for a tumor‐stage‐independent association between higher creatinine and lower albumin with worse disease‐specific survival. Low albumin and a high albumin‐creatinine‐ratio independently predict poor overall survival. Our work identified novel prognostic biomarkers for prognosis of patients with liposarcoma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:533–538, 2016.     

The impact of socioeconomic status and geographic remoteness on access to pre-emptive kidney transplantation and transplant outcomes among children

Background

Low socioeconomic status (SES) and geographic disparity have been associated with worse outcomes and poorer access to pre-emptive transplantation in the adult end-stage kidney disease (ESKD) population, but little is known about their impact in children with ESKD. The aim of our study was to determine whether access to pre-emptive transplantation and transplant outcomes differ according to SES and geographic remoteness in Australia.

Methods

Using data from the Australia and New Zealand Dialysis and Transplant Registry (1993–2012), we compared access to pre-emptive transplantation, the risk of acute rejection and graft failure, based on SES and geographic remoteness among Australian children with ESKD (≤18 years), using adjusted logistic and Cox proportional hazard modelling.

Results

Of the 768 children who commenced renal replacement therapy, 389 (50.5 %) received living donor kidney transplants and 28.5 % of these (111/389) were pre-emptive. There was no significant association between SES quintiles and access to pre-emptive transplantation, acute rejection or allograft failure. Children residing in regional or remote areas were 35 % less likely to receive a pre-emptive transplant compared to those living in major cities [adjusted odds ratio (OR) 0.65, 95 % confidence interval (CI) 0.45–1.0]. There was no significant association between geographic disparity and acute rejection (adjusted OR 1.03, 95 % CI 0.68–1.57) or graft loss (adjusted hazard ratio 1.05, 95 % CI 0.74–1.41).

Conclusions

In Australia, children from regional or remote regions are much less likely to receive pre-emptive kidney transplantation. Strategies such as improved access to nephrology services through expanding the scope of outreach clinics, and support for regional paediatricians to promote early referral may ameliorate this inequity.

     

Missed opportunities of inclusion in a cohort of HIV-infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013

Introduction

The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d''Ivoire, and Ouagadougou, Burkina Faso.

Methods

All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion.

Results

Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father''s refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child''s and mother''s HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency.

Conclusions

Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.     

Prevalence of microalbuminuria in the general population of Seychelles and strong association with diabetes and hypertension independent of renal markers

OBJECTIVE: Few studies have examined microalbuminuria (MAU) in non-western populations. We assessed the prevalence of MAU in the general population of a middle-income country in the African region and relationships between MAU and selected cardiovascular risk factors. METHODS: An examination survey was conducted in a sample representative of the entire population aged 25-64 years in the Seychelles. MAU adjusted for urine creatinine concentration was measured on the second morning urine using a semiquantitative point-of-care analyzer. RESULTS: A total of 1255 persons attended the survey (participation rate of 80.2%). The age-adjusted prevalence of MAU was 11.4%. At age 25-64 years, the prevalence of MAU was 5% in persons without diabetes and hypertension, 20% in persons with either condition and 41% in persons with both conditions. The overall prevalence of stages 3-4 chronic kidney disease was low at 3.2%. In multivariate analysis, MAU was associated with age [odds ratio (OR) 1.24 for a 10-year increase; 95% confidence interval (CI): 1.02-1.52], hypertension stage I (2.0; 1.1-3.8) and stage II (4.5; 2.3-8.6), obesity (1.7; 1.0-2.8) and diabetes (3.0; 1.9-4.9). These associations were virtually unchanged upon further adjustment for markers of renal function such as serum creatinine, serum cystatin C and calculated renal function. CONCLUSION: The prevalence of MAU was high in this population, and MAU was strongly associated with several cardiovascular risk factors independently of renal function markers. These findings suggest that MAU could be a useful marker of cardiovascular risk in this population and help identify persons in need of a specific cardiovascular risk management.     

The decoy matters! Hormonal and behavioural differences in the reaction of territorial European robins towards stuffed and live decoys

Simulated territorial intrusions (STIs) represent a commonly used experimental manipulation to test behavioural and hormonal responses of birds towards conspecific intruders. They are typically either conducted with live birds in a cage or with stuffed decoys. To our knowledge, nobody has tested whether these two different kinds of stimuli elicit the same kind of behavioural and hormonal response. We compared the reactions of European robins to STIs with stuffed and live decoys to see whether these stimuli are perceived in similar ways. We conducted STIs by placing a stuffed or a live decoy in a territory, played-back robin song and recorded the behaviour for at least 10min. Then, the focal bird was caught, and a blood sample was taken to measure hormone concentrations. Males challenged with a stuffed decoy responded with more threats and movements around the decoy than males that were exposed to a live decoy. Furthermore, males challenged with a stuffed decoy had significantly higher corticosterone levels than males challenged with a live decoy. Androgen levels did not differ between treatments. The differential behavioural and corticosterone response of robins to stuffed and live decoys suggests that robins may perceive stuffed decoys as more threatening than live decoys. Future investigations using STI experiments should be aware of the potential impact different kinds of decoys may have on the behavioural and hormonal response of birds during STIs.     

Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, α and β, in pejerrey. Both receptors’ mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males.In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors’ mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor α, but not β, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase.Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature.Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate.     

Two new large deletions in the low density lipoprotein receptor (LDLR) gene not revealed by PCR-based molecular diagnosis of familial hypercholesterolemia

In the French Canadian population six mutations appear to be responsible for about 85% of FH cases. Two of these mutations are large deletions. The most prevalent deletion is a >15 kb deletion of the promoter and first exon; the second, a 5 kb deletion that removes exons 2 and 3. The high frequency of these deletions in the French Canadian population has been attributed to a founder effect. Other mutations are present in the population but at a much lower prevalence. We recently identified two new large deletions in FH patients of French Canadian descent. Carriers of the new deletions were identified because of an unusual pattern of band migration on Southern blots. We have identified and sequenced the deletions' boundaries. The first deletion covers 3813 bp and removes exons 7 and 8. The second deletion covers 5994 bp and removes exons 3-6. These deletions have not been previously reported. They would have been missed if a PCR-based method had been used instead of Southern blot analysis.