Incidence and outcome of encapsulating peritoneal sclerosis

Background: Studies report variation in the incidence and outcomes of encapsulating peritoneal sclerosis (EPS). This study reports the incidence and outcome of EPS cases in a national cohort of peritoneal dialysis (PD) patients. Methods: The incident cohort of adult patients who started PD between 1 January 2000 and 31 December 2007 in Scotland (n = 1238) was identified from the Scottish Renal Registry. All renal units in Scotland identified potential EPS cases diagnosed from 1 January 2000 to 31 December 2014, by which point all patients had a minimum of 7 years follow-up from start of PD. Results: By 31 December 2014, 35 EPS cases were diagnosed in the 1238 patient cohort: an overall incidence of 2.8%. The incidence for subgroups with longer PD duration rises exponentially: 1.1% by 1 year, 3.4% by 3 years, 8.8% at 4 years, 9.4% at 5 years and 22.2% by 7 years. Outcomes are poor with mortality of 57.1% by 1 year after diagnosis. Survival analysis demonstrates an initial above-average survival in patients who later develop EPS, which plummets to well below average after EPS diagnosis. Conclusions: The incidence of EPS is reassuringly low provided PD exposure is not prolonged and this supports ongoing use of PD. However, continuing PD beyond 3 years results in an exponential rise in the risk of developing EPS and deciding whether this risk is acceptable should be made on an individual patient basis

Continued monitoring of acute kidney injury survivors might not be necessary in those regaining an estimated glomerular filtration rate > 60 mL/min at 1 year

Background. Severe acute kidney injury (AKI) among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who recover to normal renal function. The aim of this study was to determine the long-term renal outcome of patients experiencing AKI requiring dialysis secondary to hypoperfusion injury and/or sepsis who recovered to apparently normal renal function. Methods. All adult patients with AKI requiring dialysis in our centre between 1 January 1980 and 31 December 2010 were identified. We included patients who had estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 12 months or later after the episode of AKI. Patients were followed up until 3 March 2015. The primary outcome was time to chronic kidney disease (CKD) (defined as eGFR persistently <60 mL/min/1.73 m2) from first dialysis for AKI. Results. Among 2922 patients with a single episode of dialysis-requiring AKI, 396 patients met the study inclusion criteria. The mean age was 49.8 (standard deviation 16.5) years and median follow-up was 7.9 [interquartile range (IQR) 4.8–12.7] years. Thirty-five (8.8%) of the patients ultimately developed CKD after a median of 5.3 (IQR 2.8–8.0) years from first dialysis for AKI giving an incidence rate of 1 per 100 person-years. Increasing age, diabetes and vascular disease were associated with higher risk of progression to CKD [adjusted hazard ratios (95% confidence interval): 1.06 (1.03, 1.09), 3.05 (1.41, 6.57) and 3.56 (1.80, 7.03), respectively]. Conclusions. Recovery from AKI necessitating in-hospital dialysis was associated with a very low risk of progression to CKD. Most of the patients who progressed to CKD had concurrent medical conditions meriting monitoring of renal function. Therefore, it seems unlikely that regular follow-up of renal function is beneficial in patients who recover to eGFR >60 mL/min/1.73 m2 by 12 months after an episode of AKI

An increase in N-Ras expression is associated with development of hormone refractory prostate cancer in a subset of patients

Protein expression of H, K and N-Ras was assessed in hormone sensitive and hormone refractory prostate tumour pairs from 61 patients by immunohistochemistry. Expression of H-Ras and K- Ras was not associated with any known clinical parameters. In contrast an increase in N-Ras membrane expression in the transition from hormone sensitive to hormone refractory prostate cancer was associated with shorter time to relapse (p=0.01) and shorter disease specific survival (p=0.008). In addition, patients with an increase in N-Ras membrane expression had lower levels of PSA at relapse (p=0.02) and expression correlated with phosphorylated MAP kinase (p=0.010) and proliferation index (Ki67, p=0.02). These results suggest that in a subgroup patients N-Ras expression is associated with development of hormone refractory prostate cancer via activation of the MAP kinase cascade

The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer

<b>Purpose</b>: The role of the type I receptor tyrosine kinase (HER) family in progression of prostate cancer is controversial. Breast cancer studies show that these receptors should be investigated as a family. The current study investigates expression of HER1-HER4 and EGFRvIII in matched hormone-sensitive and hormone-refractory prostate tumors. <b>Experimental Design</b>: Immunohistochemical analysis was used to investigate protein expression of HER1-HER4, EGFRvIII, and phosphorylated Akt (pAkt) in matched hormone-sensitive and hormone-refractory prostate tumors. <b>Results</b>: Surprisingly, high HER2 membrane expression in hormone-sensitive tumors was associated with an increased time to biochemical relapse (<i>P</i> = 0.0003), and this translated into longer overall survival (<i>P</i> = 0.0021). Consistent with other studies, HER4 membrane expression in hormone-sensitive tumors was associated with longer time to biochemical relapse (<i>P</i> = 0.042), and EGFRvIII membrane expression was associated with shorter time to biochemical relapse (<i>P</i> = 0.015). An increase in pAkt expression was associated with reduced survival (<i>P</i> = 0.0098). Multivariate analysis showed that HER2 was an independent positive predictive marker of time to relapse in hormone-sensitive prostate tumors (<i>P</i> = 0.014). In contrast, high HER2 expression in hormone-refractory tumors was associated with decreased time to death from biochemical relapse (<i>P</i> = 0.039), and EGFRvIII nuclear expression was associated with decreased time to death from biochemical relapse and decreased overall survival (<i>P</i> = 0.02 and <i>P</i> = 0.005). <b>Conclusion</b>: These results suggest that the HER family may have multiple roles in prostate cancer, and that expression of the proteins alone is insufficient to predict the biological response that they may elicit

The idealization of 'compassion' in trainee nurses' talk: a psychosocial focus group study

Why do nurses in training continue to draw on the ideal of compassion when responding to their experiences of nursing work in the UK National Health Service (NHS), despite the difficulties that they face in developing compassionate, long-term relationships with patients in practice? To answer this question, we draw from a psychosocial analysis of focus groups data from 49 trainee nurses in the NHS. First, we show how the manifestation of this ideal in trainee nurses’ discourse leads them to blame qualified nurses for failures in patient care. We suggest this is an unconscious defence against the anxiety evoked both by the vulnerability of their position as those who need to gain access to the profession, and of being unable to conduct compassionate nursing work. Second, we emphasise that less powerful occupational groups, such as trainee nurses, may adopt defences that underpin dominant organizational policy, such as idealization, despite further disadvantaging their group and benefitting those in power. We conclude by questioning the particular emphasis on compassion in nurses’ training, which can prevent occupational solidarity and the ability to reflect on the structural and organizational factors required to conduct patient-centred nursing work

Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor.

The intrinsic efficacy of orthosteric ligands acting at G-protein-coupled receptors (GPCRs) reflects their ability to stabilize active receptor states (R*) and is a major determinant of their physiological effects. Here, we present a direct way to quantify the efficacy of ligands by measuring the binding of a R*-specific biosensor to purified receptor employing interferometry. As an example, we use the mu-opioid receptor (µ-OR), a prototypic class A GPCR, and its active state sensor, nanobody-39 (Nb39). We demonstrate that ligands vary in their ability to recruit Nb39 to µ-OR and describe methadone, loperamide, and PZM21 as ligands that support unique R* conformation(s) of µ-OR. We further show that positive allosteric modulators of µ-OR promote formation of R* in addition to enhancing promotion by orthosteric agonists. Finally, we demonstrate that the technique can be utilized with heterotrimeric G protein. The method is cell-free, signal transduction-independent and is generally applicable to GPCRs

Association between urinary sodium, creatinine, albumin, and long term survival in chronic kidney disease

Dietary sodium intake is associated with hypertension and cardiovascular risk in the general population. In patients with chronic kidney disease, sodium intake has been associated with progressive renal disease, but not independently of proteinuria. We studied the relationship between urinary sodium excretion and urinary sodium:creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adults attending a renal clinic who had at least one 24-hour urinary sodium measurement were identified. 24-hour urinary sodium measures were collected and urinary sodium:creatinine ratio calculated. Time to renal replacement therapy or death was recorded. 423 patients were identified with mean estimated glomerular filtration rate of 48ml/min/1.73m<sup>2</sup>. 90 patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was -2.8ml/min/1.73m<sup>2</sup>/year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher urinary sodium excretion and urinary sodium:creatinine but the association with these parameters and poor outcome was not independent of renal function, age and albuminuria. When stratified by albuminuria, urinary sodium:creatinine was a significant cumulative additional risk for mortality, even in patients with low level albuminuria. There was no association between low urinary sodium and risk, as observed in some studies. This study demonstrates an association between urinary sodium excretion and mortality in chronic kidney disease, with a cumulative relationship between sodium excretion, albuminuria and reduced survival. These data support reducing dietary sodium intake in chronic kidney disease but further study is required to determine the target sodium intake

Renal replacement modality and stroke risk in end-stage renal disease—a national registry study

Background: The risk of stroke in end-stage renal disease (ESRD) on renal replacement therapy (RRT) is up to 10-fold greater than the general population. However, whether this increased risk differs by RRT modality is unclear. Methods: We used data contained in the Scottish Renal Registry and the Scottish Stroke Care Audit to identify stroke in all adult patients who commenced RRT for ESRD from 2005 to 2013. Incidence rate was calculated and regression analyses were performed to identify variables associated with stroke. We explored the effect of RRT modality at initiation and cumulative dialysis exposure by time-dependent regression analysis, using transplant recipients as the reference group. Results: A total of 4957 patients commenced RRT for ESRD. Median age was 64.5 years, 41.5% were female and 277 patients suffered a stroke (incidence rate was 18.6/1000 patient-years). Patients who had stroke were older, had higher blood pressure and were more likely to be female and have diabetes. On multivariable regression older age, female sex, diabetes and higher serum phosphate were associated with risk of stroke. RRT modality at initiation was not. On time-dependent analysis, haemodialysis (HD) exposure was independently associated with increased risk of stroke. Conclusions: In patients with ESRD who initiate RRT, HD use independently increases risk of stroke compared with transplantation. Use of peritoneal dialysis did not increase risk on adjusted analysis

Mesenchymal stem cell response to topographically modified CoCrMo

Surface roughness on implant materials has been shown to be highly influential on the behavior of osteogenic cells. Four surface topographies were engineered on cobalt chromium molybdenum (CoCrMo) in order to examine this influence on human mesenchymal stem cells (MSC). These treatments were smooth polished (SMO), acid etched (AE) using HCl 7.4% and H2 SO4 76% followed by HNO3 30%, sand blasted, and acid etched using either 50 μm Al2 O3 (SLA50) or 250 μm Al2 O3 grit (SLA250). Characterization of the surfaces included energy dispersive X-ray analysis (EDX), contact angle, and surface roughness analysis. Human MSCs were cultured onto the four CoCrMo substrates and markers of cell attachment, retention, proliferation, cytotoxicity, and osteogenic differentiation were studied. Residual aluminum was observed on both SLA surfaces although this appeared to be more widely spread on SLA50, whilst SLA250 was shown to have the roughest topography with an Ra value greater than 1 μm. All substrates were shown to be largely non-cytotoxic although both SLA surfaces were shown to reduce cell attachment, whilst SLA50 also delayed cell proliferation. In contrast, SLA250 stimulated a good rate of proliferation resulting in the largest cell population by day 21. In addition, SLA250 stimulated enhanced cell retention, calcium deposition, and hydroxyapatite formation compared to SMO (p < 0.05). The enhanced response stimulated by SLA250 surface modification may prove advantageous for increasing the bioactivity of implants formed of CoCrMo. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2015