Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis

PMCID: PMC3686792This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III-rationale, trial design and baseline data

Background Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. Methods UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor–neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but 20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin–angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. Results Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. Conclusions UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

The writing on the wall: the concealed communities of the East Yorkshire horselads

This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor

Intravenous sildenafil citrate and post-cardiac surgery acute kidney injury: a double-blind, randomised, placebo-controlled trial

Clinical trial registration ISRCTN18386427. open access articleBackground This study assessed whether i.v. sildenafil citrate prevented acute kidney injury in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass. Methods In a double-blind RCT, adults at increased risk of acute kidney injury undergoing cardiac surgery in a single UK tertiary centre were randomised to receive sildenafil citrate 12.5 mg kg−1 i.v. over 150 min or dextrose 5% at the commencement of surgery. The primary outcome was serum creatinine measured at six post-randomisation time points. The primary analysis used a linear mixed-effects model adjusted for the stratification variables, baseline estimated glomerular filtration rate, and surgical procedure. Secondary outcomes considered clinical events and potential disease mechanisms. Effect estimates were expressed as mean differences (MDs) or odds ratios with 95% confidence intervals. Results The analysis population comprised eligible randomised patients that underwent valve surgery or combined coronary artery bypass graft and valve surgery, with cardiopulmonary bypass, between May 2015 and June 2018. There were 60 subjects in the sildenafil group and 69 in the placebo control group. The difference between groups in creatinine concentration was not statistically significant (MD: 0.88 μmol L−1 [–5.82, 7.59]). There was a statistically significant increase in multiple organ dysfunction scores in the sildenafil group (MD: 0.54 [0.02, 1.07]; P=0.044). Secondary outcomes, and biomarkers of kidney injury, endothelial function, and inflammatory cell activation, were not significantly different between the groups. Conclusions These results do not support the use of i.v. sildenafil citrate for kidney protection in adult cardiac surgery

Control of primary productivity and the significance of photosynthetic bacteria in a meromictic kettle lake.

During 1986 planktonic primary production and controlling factors were investigated in a small (A0 = 11.8 · 103 m2, Zmax = 11.5 m) meromictic kettle lake (Mittlerer Buchensee). Annual phytoplankton productivity was estimated to ca 120 gC · m–2 · a–1 (1,42 tC · lake–1 · a–1). The marked thermal stratification of the lake led to irregular vertical distributions of chlorophylla concentrations (Chla) and, to a minor extent, of photosynthesis (Az). Between the depths of 0 to 6 m low Chla concentrations (< 7 mg · m–3) and comparatively high background light attenuation (kw = 0,525 m–1, 77% of total attenuation due to gelbstoff and abioseston) was found. As a consequence, light absorption by algae was low (mean value 17,4%) and self-shading was absent. Because of the small seasonal variation of Chla concentrations, no significant correlation between Chla and areal photosynthesis (A) was observed. Only in early summer (June–July) biomass appears to influence the vertical distribution of photosynthesis on a bigger scale. Around 8 m depth, low-light adapted algae and phototrophic bacteria formed dense layers. Due to low ambient irradiances, the contribution of these organisms to total primary productivity was small. Primary production and incident irradiance were significantly correlated with each other (r2 = 0.68). Although the maximum assimilation number (Popt) showed a clear dependence upon water temperature (Q10 = 2.31), the latter was of minor importance to areal photosynthesis

Defining the Molecular Character of the Developing and Adult Kidney Podocyte

BACKGROUND: The podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease. METHODOLOGY/PRINCIPAL FINDINGS: In this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined. CONCLUSIONS/SIGNIFICANCE: The complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells

Corrigendum to: Cohort profile: Extended Cohort for E-health, Environment and DNA (EXCEED)

This is a correction to: International Journal of Epidemiology, Volume 48, Issue 3, June 2019, Pages 678–679j, https://doi.org/10.1093/ije/dyz07