Pulmonary sarcoidosis : a clinical update

Peer reviewedPublisher PD

Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients : A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Supplementary Materials: The following are available online at www.mdpi.com/2077-0383/8/2/208/s1, Supplementary Figure S1. Forest plot comparing the effects of oral bicarbonate therapy and control on serum creatinine levels. Supplementary Figure S2. Forest plot comparing the effects of oral bicarbonate therapy and control on eGFR at one year. Supplementary Figure S3. Forest plot comparing the effects of oral bicarbonate therapy and control on serum bicarbonate levels at one year. . Funding: This work was supported by a National Institute of Health Research Health Technology Assessment (NIHR HTA) project grant (Ref: 10/71/10).Peer reviewedPublisher PD

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease:the BiCARB RCT

Acknowledgements: We would like to acknowledge the support received from the NHS Scotland Support for Science scheme and the NIHR Renal and Ageing Comprehensive Research Networks; the work of all the investigators, research nurses and study teams at the different sites and the Tayside CTU staff; and, most importantly, all those with kidney disease who participated in the trial. In addition, we acknowledge the support and advice that we received from the independent TSC members (Professor David Stott, Professor Patrick Mark, Professor Tahir Masud and Mr Alex Stephen) and the independent DMC members (Professor Alex McConnachie, Professor David Wheeler, Dr Nicosha de Souza and Dr Andrew Clegg). Professor Marion McMurdo and Dr Simon Ogston were co-applicants on the original proposal, but demitted from the project on retirement and were not involved in the creation of this report. Trial registration: Current Controlled Trials ISRCTN09486651 and EudraCT 2011-005271-16. The systematic review is registered as PROSPERO CRD42018112908. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 27. See the NIHR Journals Library website for further project information.Peer reviewedPublisher PD

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Contributions D.D., A.H., S.G., S.P. and M.D. conceived the study and together with L.v.L., G.L., F.T. obtained the grant funding. AM executed the patient screening, recruitment, intervention planning, carried out all study investigations under respective specialist supervision (A.H./D.C./D.D. for magnetic resonance spectroscopy, F.T./G.L./D.D. for stable isotope investigation, S.G. for exercise intervention, S.P. for clinical supervision/management of diabetes as required, M.D. for all molecular laboratory analyses, A.M. analysed all data and performed statistical analysis under the supervision of G.H. L.v.L. provided expert advice in athletic physiology. Lipidomic analyses were carried out in P.W. laboratory. Blood/skeletal muscle enrichment analyses were carried out in B.F./F.T.-G.L. laboratories respectively, with practical input from R.G. A.R. and L.C. contributed as overall help to deliver study assessments in a technical role. M.K.H. analysed the food diaries. D.E.N. contributed to manuscript writing. D.D. and M.D. were the PhD supervisors for A.M. whose PhD thesis was based on this work. All authors contributed their respective specialist sections in drafting the manuscript.Peer reviewe

Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction

The Engineering and Sciences Library was formed in 1990,incorporating the C. S. Davis Mathematics Library and the Thomas Parnell Memorial Physics Library. In 1997 the library was refurbished and merged with the Geology Library collection. The library was named the Dorothy Hill Physical Sciences and Engineering Library, after the late Professor Dorothy Hill, and opened officially on 26 August 1997. In 2011, the name was changed to the Dorothy Hill Engineering and Sciences Library, when the collections were merged with those of the Biological Sciences Library

Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction

BACKGROUND. Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and there is an established association between vasculopathy affecting the kidney and eye. Optical coherence tomography (OCT) is a novel, rapid method for high-definition imaging of the retina and choroid. Its use in patients at high cardiovascular disease risk remains unexplored. METHODS. We used the new SPECTRALIS OCT machine to examine retinal and retinal nerve fiber layer (RNFL) thickness, macular volume, and choroidal thickness in a prospective cross-sectional study in 150 subjects: 50 patients with hypertension (defined as a documented clinic BP greater than or equal to 140/90 mmHg (prior to starting any treatment) with no underlying cause identified); 50 with CKD (estimated glomerular filtration rate (eGFR) 8–125 ml/min/1.73 m(2)); and 50 matched healthy controls. We excluded those with diabetes. The same, masked ophthalmologist carried out each study. Plasma IL-6, TNF-α , asymmetric dimethylarginine (ADMA), and endothelin-1 (ET-1), as measures of inflammation and endothelial function, were also assessed. RESULTS. Retinal thickness, macular volume, and choroidal thickness were all reduced in CKD compared with hypertensive and healthy subjects (for retinal thickness and macular volume P < 0.0001 for CKD vs. healthy and for CKD vs. hypertensive subjects; for choroidal thickness P < 0.001 for CKD vs. healthy and for CKD vs. hypertensive subjects). RNFL thickness did not differ between groups. Interestingly, a thinner choroid was associated with a lower eGFR (r = 0.35, P <0.0001) and, in CKD, with proteinuria (r = –0.58, P < 0.001) as well as increased circulating C-reactive protein (r = –0.57, P = 0.0002), IL-6 (r = –0.40, P < 0.01), ADMA (r = –0.37, P = 0.02), and ET-1 (r = –0.44, P < 0.01). Finally, choroidal thinning was associated with renal histological inflammation and arterial stiffness. In a model of hypertension, choroidal thinning was seen only in the presence of renal injury. CONCLUSIONS. Chorioretinal thinning in CKD is associated with lower eGFR and greater proteinuria, but not BP. Larger studies, in more targeted groups of patients, are now needed to clarify whether these eye changes reflect the natural history of CKD. Similarly, the associations with arterial stiffness, inflammation, and endothelial dysfunction warrant further examination. TRIAL REGISTRATION. Registration number at www.clinicalTrials.gov: NCT02132741. SOURCE OF FUNDING. TR was supported by a bursary from the Erasmus Medical Centre, Rotterdam. JJMHvB was supported by a bursary from the Utrecht University. JRC is supported by a Rowling Scholarship. SB was supported by a Wellcome Trust funded clinical research fellowship from the Scottish Translational Medicine and Therapeutics Initiative, and by a Rowling Scholarship, at the time of this work. ND is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/13/30/29994)

Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called “athlete’s paradox”. In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY)

Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis : The BiCARB randomised controlled trial

FUNDING The BiCARB trial was funded by the National Institute for Health Research Health Technology Assessment programme (project reference 10/71/01). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The funder of the study had input into the study design via the original commissioning call specification. The funder had no other role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit. Disclaimer: The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate. Acknowledgements We acknowledge the support received via the NHS Scotland Support for Science scheme; the NIHR Renal and Ageing Comprehensive Research Networks; and the work of all of the research nurses, local investigators and study teams at sites; Tayside Clinical Trials Unit staff; and most importantly all those with kidney disease who participated in the trial. Professor Witham acknowledges support from the NIHR Newcastle Biomedical Research Centre. In addition, we acknowledge the support and advice we received from the independent Trial Steering Committee members (Professor David Stott, Professor Patrick Mark, Professor Tahir Masud and Mr. Alex Stephen) and the independent Data Monitoring Committee (Professor Alex McConnachie, Professor David Wheeler, Dr. Nicosha de Souza, Professor Andrew Clegg). We also acknowledge the efforts of all the investigators, site research nurses and support teams.Peer reviewe